AGENT IDE: A Prospective, Randomized (2:1), Multicenter Trial to Assess the Safety and Effectiveness of the AgentTM Paclitaxel Coated PTCA Balloon Catheter for the Treatment of Subjects With In-Stent Restenosis (ISR)
Phase: PHASE3
Conditions: In-Stent Restenosis
Sponsor: Boston Scientific Corporation

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 1  of 9 0  
 
 
 
 
A G E N T I D E  
A Pr os pecti ve, Ra n d o mize d ( 2: 1), M ulti ce nter Trial t o A ssess t he Safet y a n d E ffecti ve ness of 
t he A ge ntT M  Paclita xel C oate d P T C A Ball o o n Cat heter f or t he Treat me nt of S u bjects wit h  
In -S te nt R este n osis (I S R)  
 
S 2 3 5 8  
C LI NI C A L I N V E S TI G A TI O N P L A N 
 
I D E #: G 2 0 0 1 0 0 
 
N ati o n al Cli nic al Tri al ( N C T) #: N C T 0 4 6 4 7 2 5 3  
 
 
S p o ns ore d B y  
B ost o n Scie ntific C or p orati o n  
3 0 0 B ost o n Scie ntific  Wa y  
Marl b or o u g h, M A 0 1 7 5 2, U nite d States  
 
 
 
 
T his pr ot oc ol c o nt ai ns c o nfi de nti al i nf or m ati o n f or use b y t he I n vesti gat ors a n d t heir 
desi g nate d re prese ntati ves partici pati n g i n t his cli nical i n vesti gati o n. T he pr ot oc ol  s h o ul d be 
hel d c o nfi de ntial a n d mai ntai ne d i n a sec ure l ocati o n . 
D o n ot c o py or distri b ute wit h o ut writte n per missi o n fr o m B ost o n Scie ntific C or p or ati o n.  
 
 
 
 
 
 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 2  of 9 0  
  
 
 
C o nt act I nf or m ati o n  
R ole  
C o nt act  
B S C Cli nic al C o nt act  
Patricia O’ Mara  
Cli nical Trial Ma na ger  
Cli nical, I nter ve nti o nal Car di ol o g y  
1 0 0 B ost o n Scie ntific Wa y    
Marl b or o u g h, M A 0 1 7 5 2 U S A  
 
Patricia. o mara @ bsci.c o m  
 
C o or di n ati n g Pri nci p al 
I n vesti g at or(s) 
 
R o bert Ye h, M D  
Bet h Israel Deac o ness Me dical Ce nter  
3 3 0 Br o o kli ne A ve  
B ost o n, M A  
 
r ye h @ bi d mc. har var d.e d u 
 
Ve n d ors/ L a bs  
A list of ve n d ors/la b o rat ories i n v ol ve d i n t he trial is mai ntai ne d 
b y t he s p o ns or .  
 
 
 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 3  of 9 0  
 
O ri gi n al Rele ase:  2 7 Marc h 2 0 2 0  
C urre nt Versi o n:  1 4 A pril 2 0 2 3  
  
 
  
 
Re visi o n 
Versi o n  
Pr ot oc ol  
D ate  
Te m pl ate 
n u m ber 
a n d 
versi o n  
Pr ot oc ol 
Secti o n  
M o difie
d  
S u m m ar y of C h a n ges  
 
J ustific ati o n f or 
M o dific ati o n  
A   
2 7 Marc h 
2 0 2 0  
9 0 7 0 2 6 3 7 
Re v/ Ver 
A L  
N/ A  
N/ A  
I nitial Release  
B  
0 2 
Oct o ber  
2 0 2 0  
9 0 7 0 2 6 3 7  
Re v/ Ver 
A N   
Secti o n 
6, 7 8, 9, 
1 0 , 1 1 
a n d 18    
Secti o n 6 : lesi o n le n gt h t o 
be treate d 2 6  m m  
Secti o n  7 : ma xi m u m 
n u m ber of s u bjects t hat 
ca n cr oss o ver fr o m A ge nt 
t o P O B A ar m  
Secti o n 8 : I ncl usi o n 
criteria: lesi o n le n gt h 2 6 
m m; E xcl usi o n criteria:  
rece nt C O VI D patie nts 
Secti o n 9 : S u bject 
wit h dra wal la n g ua ge 
u p date d  
Secti o n 1 0 : Preferre d 
car diac e nz y me is C K -
M B; a nti platelet t hera p y 
u p date d  
Secti o n 1 1 :  A d diti o nal 
s u b-gr o u p a nal ysis a d de d  
Secti o n 1 8:  A d diti o nal 
ris k a d de d 
U p date d pr ot oc ol 
per F D A desi g n 
rec o m me n dati o ns 
C  
0 9 
Dece m ber  
2 0 2 0  
9 0 7 0 2 6 3 7 
Re v/ Ver 
A O   
Secti o n 
7, 8, 1 0, 
1 1, 1 9 
a n d 2 3 
Secti o n 7: i ncrease 
n u m ber of s u bjects , a d d 
stratificati o n b y ce nter 
a n d ste nt la yer  a n d clarif y 
pers o n nel bli n di n g . 
U p date t o st u d y 
sc he matic.  
Secti o n 8: U p date 
I ncl usi o n/ E xcl usi o n 
criteria.  
Secti o n 1 0:  U p date 
A nti platelet t hera p y . 
Secti o n 1 1: U p date 
statistical c o nsi derati o ns.   
Secti o n 1 9:  A d d Seri o us 
Healt h T hreat defi niti o n . 
U p date d pr ot oc ol 
per Steeri n g 
C o m mittee 
rec o m me n dati o ns 
a n d u p date d B S C 
te m plate.  

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 4  of 9 0  
  
  
 
  
 
Re visi o n 
Versi o n  
Pr ot oc ol  
D ate  
Te m pl ate 
n u m ber 
a n d 
versi o n  
Pr ot oc ol 
Secti o n  
M o difie
d  
S u m m ar y of C h a n ges  
 
J ustific ati o n f or 
M o dific ati o n  
Secti o n 2 3: A d d St u d y 
Re gistrati o n la n g ua ge .  
D  
0 1 
Oct o ber 
2 0 2 1  
9 0 7 0 2 6 3 7 
Re v/ Ver 
A P  
 
Versi o n D of pr ot oc ol n ot 
i m ple me nte d  
N A  
E  
2 5 Marc h 
2 0 2 2  
9 0 7 0 2 6 3 7 
Re v/ Ver 
A P  
 
Versi o n E of pr ot oc ol n ot 
i m ple me nte d  
N A  
F   
2 5 
Oct o ber  
2 0 2 2  
9 0 7 0 2 6 3 7 
Re v/ Ver 
A Q  
  
Clarif y t he a da pti ve 
desi g n wit h f or mal 
i nteri m a nal ysis.  
U p date safet y re p orti n g 
secti o n t o ali g n wit h 
c urre nt pr ot oc ol te m plate.  
Clarif yi n g t he 
a da pti ve desi g n 
a n d statistical 
met h o d per F D A 
rec o m me n dati o n.  
G   
1 4 A pril 
2 0 2 3  
9 0 7 0 2 6 3 7 
Re v/ Ver 
A Q  
Secti o n 
2, 6, 1 1 
a n d 2 5 
Clarif yi n g t he a nal ysis of 
MI t o i ncl u de t he peri -
pr oce d ural MI ( P P MI) 
acc or di n g t o t he S C AI 
defi niti o n a n d 
s p o nta ne o us MI acc or di n g 
t o t he 4t h U ni versal MI 
defi niti o n.  
C orrect defi niti o n of 
tec h nical s uccess 
Clarif y t he 
a nal ysis of car diac 
e nz y me data a n d 
MI per F D A 
rec o m me n dati o n. 
 
  
 
 
 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 6  of 9 0  
  
A G E N T I D E St u d y ( S 2 3 5 8) 
A Pr os pecti ve, Ra n d o mize d ( 2: 1), M ulti ce nter Trial t o A ssess t he Safet y a n d E ffecti ve ness 
of t he A ge nt T M  Paclita xel C oate d P T C A Ball o o n Cat heter f or t he Treat me nt of S u bjects  
wit h  In -S te nt R este n osis (I S R)  
Pl a n ne d 
N u m ber of 
I n vesti g ati o n al 
Sites  
U p t o 4 0  sites i n t he U nite d States  
 
Pri m ar y  
E n d p oi nt  
T he pri mar y e n d p oi nt is t he 1 2 -m o nt h Tar get Lesi o n Fail ure ( T L F) rate, 
defi ne d as a n y isc he mia -dri ve n re vasc ularizati o n of t he tar get lesi o n 
( T L R), m y ocar dial i nfarcti o n ( MI, Q-wa ve a n d n o n – Q -wa ve) relate d t o 
t he tar get vessel, or car diac deat h. T he MI e ve nts i ncl u de t he Peri -
Pr oce d ural MI ( P P MI) acc or di n g t o t he S C AI MI defi niti o n a n d t he 
s p o nta ne o us MI acc or di n g t o t he 4 t h U ni versal MI defi niti o n . 
A d diti o n al 
E n d p oi nts  
Cli nical e n d p oi nts meas ure d i n -h os pital a n d at 3 0  da ys, 6  m o nt hs, 1 2 
m o nt hs, t he n a n n uall y t hr o u g h 5 years.  
• 
T ar get lesi o n re vasc ularizati o n ( T L R) rate, Tar get lesi o n fail ure 
( T L F) rate ( pri mar y e n d p oi nt at 1 2  m o nt hs), Tar get vessel 
re vasc ularizati o n ( T V R) rate  
• 
Tar get vessel fail ure ( T V F) rate  
• 
MI ( Q -wa ve a n d n o n – Q -wa ve) rate  (P P MI per t he S C AI 
defi niti o n  a n d s p o nta ne o us MI per 4 t h U ni versal defi niti o n ) 
• 
Car diac deat h  rate,  
• 
N o n -car diac deat h  rate 
• 
All -ca use deat h rate  
• 
Ste nt t hr o m b osis rates ( per  Aca de mic Researc h C o ns orti u m 
[ A R C] defi niti o ns) 
Peri pr oce d ural e n d p oi nt:  
• 
Cli nical pr oce d ural s uccess rate  
• 
Tec h nical s uccess rate    
C ha n ge i n Q ualit y of Life:  
• 
F u ncti o nal stat us of ge neral healt h -relate d q ualit y of life 
meas ure d b y c ha n ges i n E Q -5 D sc ores at h os pital disc har ge, 1 2 
m o nt hs, 2 4  m o nt hs a n d 3 6  m o nt hs . 
Met h o d of 
Assi g ni n g 
P atie nts t o 
Tre at me nt  
After s uccessf ul pre -treat me nt of t he lesi o n a n d c o nfir mati o n t hat 
i ncl usi o n/e xcl usi o n criteria ha ve bee n met, s u bjects will be ra n d o mize d 
( 2: 1) t o recei ve eit her t he test de vice or a c o ntr ol de vice. A s u bject will 
be c o nsi dere d e nr olle d at t he ti me of ra n d o mizati o n.  

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 7  of 9 0  
  
A G E N T I D E St u d y ( S 2 3 5 8) 
A Pr os pecti ve, Ra n d o mize d ( 2: 1), M ulti ce nter Trial t o A ssess t he Safet y a n d E ffecti ve ness 
of t he A ge nt T M  Paclita xel C oate d P T C A Ball o o n Cat heter f or t he Treat me nt of S u bjects  
wit h  In -S te nt R este n osis (I S R)  
F oll o w -u p 
Sc he d ule  
Cli nical f oll o w -u p: i n h os pital, 3 0 da ys, 6  m o nt hs, 1 2 m o nt hs, t he n 
a n n uall y t hr o u g h 5 years p ost i n de x pr oce d ure . 
 
T he st u d y will be c o nsi dere d c o m plete wit h re gar d t o  t he pri mar y 
e n d p oi nt after all s u bjects ha ve c o m plete d t he 1 2 -m o nt h  f oll o w-u p 
peri o d.  S u bjects w h o are e nr olle d b ut w h o d o n ot recei ve a st u d y / 
c o ntr ol  de vice  will be f oll o we d t hr o u g h 1 2  m o nt hs o nl y . 
St u d y  
D ur ati o n  
E nr olle d s u bjects will be f oll o we d f or 5  years f oll o wi n g t he i n de x 
pr oce d ure . 
A nti pl atelet 
T her a p y  
It is re q uire d t hat s u bjects recei ve a mi ni m u m of 1 -m o nt h d ual 
a nti platelet t hera p y .  A nti platelet m o n ot hera p y  s h o ul d be c o nti n ue d f or 
t he d urati o n of t he st u d y.  
Cli nic al 
I ncl usi o n 
Criteri a  
CI 1.  
S u bject m ust be at least 1 8  years of a ge  
CI 2.  
S u bject ( or le gal g uar dia n) u n dersta n ds t he trial re q uire me nts 
a n d t he treat me nt pr oce d ures , a n d pr o vi des writte n i nf or me d 
c o nse nt bef ore a n y trial -s pecific tests or pr oce d ures are 
perf or me d  
CI 3.  
S u bject is eli gi ble f or perc uta ne o us c or o nar y i nter ve nti o n ( P CI)  
CI 4.  
S u bject is willi n g t o c o m pl y wit h all pr ot oc ol -re q uire d f oll o w-u p 
e val uati o n 
CI 5.  
W o me n of c hil d -beari n g p ote ntial m ust a gree t o use a relia ble  
met h o d  of c o ntrace pti o n fr o m t he ti me of scree ni n g t hr o u g h 1 2 
m o nt hs after t he i n de x pr oce d ure  
A n gi o gr a p hic 
I ncl usi o n 
Criteri a  ( vis u al 
esti m ate)  
AI 1.  I n-ste nt reste n osis i n a lesi o n pre vi o usl y treate d wit h eit her a 
dr u g -el uti n g ste nt or bare metal ste nt, l ocate d i n a nati ve 
c or o nar y arter y wit h a vis uall y esti mate d refere nce vessel 
dia meter ( R V D) > 2. 0 m m a n d ≤ 4. 0 m m.  
AI 2.  Tar get lesi o n le n gt h m ust be < 2 6  m m ( b y vis ual esti mate) a n d 
m ust be c o vere d b y o nl y o ne ball o o n.  
AI 3.  Tar get lesi o n m ust ha ve vis uall y esti mate d ste n osis > 5 0 % a n d < 
1 0 0 % i n s y m pt o matic patie nts  ( > 7 0 % a n d < 1 0 0 % i n 
as y m pt o matic patie nts)  pri or t o lesi o n pre -dilati o n . 
AI 4.   Tar get lesi o n m ust be s uccessf ull y pre -dilate d .  

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 8  of 9 0  
  
A G E N T I D E St u d y ( S 2 3 5 8) 
A Pr os pecti ve, Ra n d o mize d ( 2: 1), M ulti ce nter Trial t o A ssess t he Safet y a n d E ffecti ve ness 
of t he A ge nt T M  Paclita xel C oate d P T C A Ball o o n Cat heter f or t he Treat me nt of S u bjects  
wit h  In -S te nt R este n osis (I S R)  
N ote : S uccessf ul pre dilati o n/ pretreat me nt refers t o dilati o n wit h a 
ball o o n cat heter of a p pr o priate le n gt h a n d dia meter, or 
pretreat me nt wit h directi o nal or r otati o nal c or o nar y at herect o m y, 
laser or c utti n g/sc ori n g ball o o n wit h n o greater t ha n 5 0 % 
resi d ual sten osis a n d n o dissecti o n greater t ha n Nati o nal Heart, 
L u n g, Bl o o d I nstit ute ( N H L BI) t y pe C.  T hr o m b ol ysis i n 
M y ocar dial I nfarcti o n ( TI MI) gra de fl o w i n t he tar get lesi o n 
m ust be > 2  
AI 5.   If a n o n-tar get lesi o n is treate d, it m ust be treate d first a n d m ust 
be dee me d a s uccess.  
N ote:  S uccessf ul treat me nt of a n o n -tar get lesi o n is defi ne d as a 
resi d ual ste n osis of ≤ 3 0 % i n 2 near -ort h o g o nal pr ojecti o ns wit h 
TI MI 3 fl o w, as vis uall y assesse d b y t he p h ysicia n, wit h o ut t he 
occ urre nce of pr ol o n ge d c hest pai n or E C G c ha n ges c o nsiste nt 
wit h MI.  
Cli nic al 
E xcl usi o n 
Criteri a  
C E 1.  S u bject  has ot her seri o us me dical ill ness (e. g.  ca ncer, c o n gesti ve 
heart fail ure) t hat ma y re d uce life e x pecta nc y t o less t ha n 2 4 
m o nt hs.  
C E 2 .  S u bject  has c urre nt pr o ble ms wit h s u bsta nce a b use (e. g. alc o h ol, 
c ocai ne, her oi n, etc.).  
C E 3 .  S u bject has pla n ne d pr oce d ure t hat ma y ca use n o n -c o m plia nce 
wit h t he pr ot oc ol or c o nf o u n d data i nter pretati o n.  
C E 4 .  S u bject  is partici pati n g i n a n ot her i n vesti gati o nal dr u g or de vice 
cli nical st u d y t hat has n ot reac he d its pri mar y e n d p oi nt.  
C E 5 . S u bject  i nte n ds t o partici pate i n a n ot her i n vesti gati o nal dr u g or 
de vice cli nical st u d y wit hi n 1 2 m o nt hs after t he i n de x pr oce d ure.  
C E 6 .  W o ma n w h o is pre g na nt or n ursi n g. ( A pre g na nc y test m ust be 
perf or me d wit hi n 7 da ys pri or t o t he i n de x pr oce d ure, e xce pt f or 
w o me n w h o defi nitel y d o n ot ha ve c hil d -beari n g p ote ntial.)  
C E 7 .  Left ve ntric ular ejecti o n fracti o n k n o w n t o be < 2 5 % . 
C E 8 .  S u bject  ha d P CI or  ot her c or o nar y i nter ve nti o ns wit hi n t he last 
3 0 da ys.  
C E 9 .  Pla n ne d P CI or C A B G after t he i n de x pr oce d ure . 
C E 1 0 .  S T E MI or Q W MI < 7 2 h  pri or t o t he i n de x pr oce d ure . 
C E 1 1 .  Car di o ge nic s h oc k ( S B P < 8 0 m m H g re q uiri n g i n otr o pes, I A B P 
or fl ui d s u p p ort).  

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 9  of 9 0  
  
A G E N T I D E St u d y ( S 2 3 5 8) 
A Pr os pecti ve, Ra n d o mize d ( 2: 1), M ulti ce nter Trial t o A ssess t he Safet y a n d E ffecti ve ness 
of t he A ge nt T M  Paclita xel C oate d P T C A Ball o o n Cat heter f or t he Treat me nt of S u bjects  
wit h  In -S te nt R este n osis (I S R)  
C E 1 2 . K n o w n aller gies a gai nst p aclita xel or ot her c o m p o ne nts of t he 
use d me dical de vices . 
C E 1 3 .  K n o w n h y perse nsiti vit y or c o ntrai n dicati o n f or c o ntrast d ye t hat 
i n t he o pi ni o n of t he i n vesti gat or ca n n ot be a de q uatel y pre-
me dicate d.  
C E 1 4 .  I nt olera nce t o a nti platelet dr u gs, a ntic oa g ula nts re q uire d f or 
pr oce d ure.  
C E 1 5 .  Platelet c o u nt < 1 0 0 k/ m m 3 (ris k of blee di n g) or > 7 0 0 k/ m m 3 . 
C E 1 6 . S u bject  wit h re nal i ns ufficie nc y (creati ni ne ≥2. 0 m g/ dl) or 
fail ure ( dial ysis de pe n de nt). 
C E 1 7.  S u bject has s us pecte d or pr o ve n C O VI D -1 9 at prese nt or wit hi n 
t he past 4 wee ks  wit h res ol uti o n of s y m pt o ms.  
A n gi o gr a p hic 
E xcl usi o n 
Criteri a ( vis u al 
esti m ate)  
A E 1. Tar get lesi o n is l ocate d wit hi n a bif urcati o n wit h pla n ne d 
treat me nt of si de bra nc h vessel. 
A E 2. Tar get lesi o n is l ocate d wit hi n a sa p he n o us vei n or arterial graft .  
A E 3 . T hr o m b us prese nt i n t he tar get vessel. 
A E 4 . > 5 0 % ste n osis of a n a d diti o nal lesi o n pr o xi mal or cli nicall y 
si g nifica nt distal ( > 2. 0 m m R V D) t o t he tar get lesi o n. 
A E 5 .  Patie nt wit h u n pr otecte d left mai n c or o nar y arter y disease.  ( > 5 0 % 
dia meter ste n osis)  
M ulti ple 
I nter ve nti o ns 
D uri n g I n de x 
Pr oce d ure  
U p t o 2  nati ve c or o nar y arter y lesi o ns i n 2 maj or e picar dial vessels ma y 
be treate d.   S u bjects ma y ha ve 1 tar get lesi o n, or 1 tar get lesi o n a n d 1 
n o n -tar get lesi o n (i n n o n-tar get vessel) treate d.   
O ne lesi o n m ust meet t he a n gi o gra p hic criteria f or a tar get lesi o n as 
descri be d a b o ve a n d  is a p pr o priate t o be treate d wit h st u d y / c o ntr ol 
de vice . 
A ma xi m u m of 1 n o n -tar get lesi o n i n 1 n o n-tar get vessel ma y be treate d 
d uri n g t he i n de x pr oce d ure  wit h a c o m merciall y a vaila ble de vice . T he 
n o n -tar get lesi o n m ust  be treate d d uri n g t he i n de x pr oce d ure pri or t o t he 
treat me nt of t he tar get lesi o n a n d dee me d a n a n gi o gra p hic s uccess. 
St atistic al Met h o ds  

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 1 0  of 9 0  
  
A G E N T I D E St u d y ( S 2 3 5 8) 
A Pr os pecti ve, Ra n d o mize d ( 2: 1), M ulti ce nter Trial t o A ssess t he Safet y a n d E ffecti ve ness 
of t he A ge nt T M  Paclita xel C oate d P T C A Ball o o n Cat heter f or t he Treat me nt of S u bjects  
wit h  In -S te nt R este n osis (I S R)  
Pri m ar y 
St atistic al 
H y p ot hesis  
T he pri mar y e n d p oi nt of Tar get Lesi o n Fail ure at 1 2 m o nt hs f or t he 
A ge nt D C B  ar m is s u peri or t o t hat f or t he P O B A ar m.  
St atistic al Test 
Met h o d  
A z-test wit h u n p o ole d  varia nce f or t he differe nce of t w o pr o p orti o ns 
will be use d t o test t he h y p ot hesis of s u peri orit y of D C B o ver P O B A i n 
t he 1 2 -m o nt h  cli nical e n d p oi nt:  
H 0: T L FD C B  ≥ T L F P O B A   
H 1: T L FD C B  < T L F P O B A   
w here T L F D C B  a n d T L F P O B A  are t he T L F t hr o u g h 1 2  m o nt hs  f or t he 
D C B a n d P O B A ar ms res pecti vel y.  
T he pri mar y a nal ysis set f or t he pri mar y e n d p oi nt is t he I nte nt t o treat 
a nal ysis set. T his e n d p oi nt will als o be a nal yze d f or t he per pr ot oc ol 
a nal ysis set. 
S a m ple Size 
P ar a meters  
T he sa m ple size calc ulati o n f or t he pri mar y e n d p oi nt is base d o n t he 
f oll o wi n g ass u m pti o ns: 
• 
E x pecte d T L F D C B  = 1 0. 6 %  (base d o n meta -a nal ysis of hist orical 
trials a n d i ncl u di n g a n a dj ust me nt t o acc o u nt f or t he oc ul o-
ste n otic refle x)  
• 
E x pecte d T L F P O B A  = 2 1. 2 % ( base d o n meta-a nal ysis of hist orical 
trials a n d i ncl u di n g a n a dj ust me nt t o acc o u nt f or t he oc ul o-
ste n otic refle x)  
• 
Test si g nifica nce le vel ( ) = 2. 5 % ( 1 -si de d) 
• 
P o wer =  8 5 %  
• 
Ra n d o mizati o n rati o = 2 D C B: 1 P O B A  
• 
N u m ber of e val ua ble s u bjects per ar m = 3 1 0  D C B + 1 5 5  P O B A  
• 
E x pecte d attriti o n rate = 3 %  
• 
T otal pla n ne d e nr oll me nt = 4 8 0  s u bjects, 3 2 0 i n D C B a n d 1 6 0 i n 
P O B A  
• 
T he sa m ple size re-esti mati o n will be  perf or me d o n  t he pla n ne d 
f or mal i nteri m a nal ysis b y t he I n de pe n de nt D M C  Statisticia n s.  
T he fi nal sa m ple size ma y be i ncrease d u p t o a ma xi m u m of 6 0 0 
s u bjects w hic h is base d o n t he o bser ve d c o n diti o nal p o wer of t he 
i nteri m a nal ysis. Details of t his a da pti ve a p pr oac h are pre-
s pecifie d i n t he statistical a nal ysis pla n ( S A P). 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 1 1  of 9 0  
  
A G E N T I D E St u d y ( S 2 3 5 8) 
A Pr os pecti ve, Ra n d o mize d ( 2: 1), M ulti ce nter Trial t o A ssess t he Safet y a n d E ffecti ve ness 
of t he A ge nt T M  Paclita xel C oate d P T C A Ball o o n Cat heter f or t he Treat me nt of S u bjects  
wit h  In -S te nt R este n osis (I S R)  
S uccess Criteri a 
f or t he Pri m ar y 
E n d p oi nt  
T he  fi nal a nal ysis wit h t he sa m ple size deri ve d fr o m t he sa m ple size re -
esti mati o n strate g y will be c o n d ucte d o n s u bjects  wit h 1 year data . If t he 
P val ue fr o m t he z-test wit h u n p o ole d  varia nce f or t he differe nce of t w o 
pr o p orti o ns is less t ha n 0. 0 2 5 ( 1 -si de d) a n d t he e ve nt rate i n t he D C B 
gr o u p is less t ha n t he rate i n t he P O B A gr o u p  i n t he fi nal a nal ysis, t he 
pri mar y e n d p oi nt f or t he D C B will be c o ncl u de d t o be statistical l y 
si g nifica ntl y l o wer t ha n t hat f or t he P O B A. T his c orres p o n ds t o t he o ne -
si de d 9 7. 5 %  u p per  c o nfi de nce  b o u n d o n t he differe nce bet wee n 
treat me nt gr o u ps (D C B  mi n us P O B A ) f or t he o bser ve d rate of t he 
pri mar y e n d p oi nt bei n g less t ha n zer o. 
  
 
 
 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 1 2  of 9 0  
  
 
3.  T a ble of C o nte nts  
1.  T I T L E P A G E  .......................................................................................................................1  
2.  
P R O T O C O L S Y N O P SI S  .........................................................................................................5  
3.  
T A B L E O F C O N T E N T S  .......................................................................................................1 2  
 T a ble of Fi g ures  .....................................................................................................1 5  
 T a ble of T a bles  ......................................................................................................1 6  
4.  
IN T R O D U C TI O N  .................................................................................................................1 7  
 B ac k gr o u n d  ............................................................................................................1 7  
 Cli nic al B ac k gr o u n d  .............................................................................................1 8  
4. 2. 1.  
A G E N T I S R Pr os pecti ve Ra n d o mize d Trial  ............................................1 8  
 St u d y R ati o n ale  .....................................................................................................2 1  
5.  
D E VI C E D E S C RI P TI O N  ......................................................................................................2 2  
 De vice C o m p o ne nt Descri pti o n  ............................................................................2 2  
 Dr u g C o m p o ne nt Descri pti o n a n d C o ati n g F or m ul ati o n ..................................2 4  
5. 2. 1.  
Dr u g D ose  .................................................................................................2 5  
 P h ar m ac o d y n a mics  ...............................................................................................2 6  
 P h ar m ac o ki netics  ..................................................................................................2 6  
 De vice L a beli n g  .....................................................................................................2 7  
6.  
S T U D Y O B J E C TI V E S A N D E N D P OI N T S  ..............................................................................2 7  
 Pri m ar y E n d p oi nt  .................................................................................................2 7  
 A d diti o n al E n d p oi nts  ............................................................................................2 7  
7.  
S T U D Y D E SI G N  .................................................................................................................2 8  
 Sc ale a n d D ur ati o n  ................................................................................................2 8  
 Tre at me nt Assi g n me nt  ..........................................................................................3 0  
7. 2. 1.  
Tar get a n d N o n -tar get Lesi o ns .................................................................3 0  
 J ustific ati o n f or t he St u d y Desi g n  ........................................................................3 1  
8.  
S U B J E C T S E L E C TI O N  ........................................................................................................3 2  
 St u d y P o p ul ati o n a n d Eli gi bilit y  ..........................................................................3 2  
 I ncl usi o n Criteri a ..................................................................................................3 2  

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 1 3  of 9 0  
  
 E xcl usi o n Criteri a  .................................................................................................3 3  
9.  
S U B J E C T A C C O U N T A BI LI T Y  .............................................................................................3 5  
 P oi nt of E nr oll me nt  ...............................................................................................3 5  
 Wit h dr a w al  ............................................................................................................3 5  
 L ost t o F oll o w -U p  ..................................................................................................3 6  
 E n d -of -St u d y Defi niti o n ........................................................................................3 6  
 E nr oll me nt C o ntr ols  .............................................................................................3 6  
1 0.  S T U D Y M
E T H O D S  .............................................................................................................3 6  
 D at a C ollecti o n  ......................................................................................................3 6  
 St u d y C a n di d ate Scree ni n g  ..................................................................................3 9  
 I nf or me d C o nse nt ..................................................................................................3 9  
 B aseli ne / Scree ni n g  ...............................................................................................3 9  
 Re q uire d C o nc o mit a nt Me dic ati o ns  ....................................................................4 0  
 C ar di ac C at heteriz ati o n  .......................................................................................4 1  
 E n d of t he I n de x Pr oce d ure  .................................................................................4 2  
 P ost pr oce d ure/ Disc h ar ge  .....................................................................................4 2  
 A n gi o gr a p h y  ..........................................................................................................4 2  
 
F oll o w -U p  ................................................................................................4 3  
 
S o urce D oc u me nts  ..................................................................................4 5  
 
A n gi o c ore l a b d oc u me nt ati o n  ...............................................................4 5  
1 1.  S T A TI S TI C A L C O N SI D E R A TI O N S  ......................................................................................4 5  
 E n d p oi nts  ...............................................................................................................4 5  
1 1. 1. 1.  Pri mar y E n d p oi nt  ......................................................................................4 5  
1 1. 1. 1. 1.  H y p ot heses  ...............................................................................4 5  
1 1. 1. 1. 2.  Sa m ple Size  ..............................................................................4 6  
 Ge ner al St atistic al Met h o ds  .................................................................................4 7  
1 1. 2. 1.  A nal ysis Sets  .............................................................................................4 7  
1 1. 2. 2.  C o ntr ol of S yste matic Err or/ Bias  ..............................................................4 7  
1 1. 2. 3.  N u m ber of S u bjects per I n vesti gati ve Site  ...............................................4 8  
 D at a A n al yses  ........................................................................................................4 8  
1 1. 3. 1.  A nal ysis of MI E ve nts  ..............................................................................4 8  
1 1. 3. 2.  Ot her E n d p oi nts/ Meas ure me nts  ................................................................4 8  
1 1. 3. 3.  I nteri m A nal yses .......................................................................................4 8  

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 1 4  of 9 0  
  
1 1. 3. 4.  S u b gr o u p A nal yses  ...................................................................................4 8  
1 1. 3. 5.  J ustificati o n of P o oli n g .............................................................................4 9  
1 1. 3. 6.  M ulti varia ble A nal yses  .............................................................................4 9  
1 1. 3. 7.  C ha n ges t o Pla n ne d A nal yses  ...................................................................4 9  
1 2.  Q U A LI T Y O F L I F E .............................................................................................................4 9  
1 3.  D A T A M
A N A G E M E N T  .......................................................................................................5 0  
 D at a C ollecti o n, Pr ocessi n g, a n d Re vie w  ............................................................5 0  
 D at a Rete nti o n  .......................................................................................................5 0  
 C ore L a b or at ories  .................................................................................................5 1  
1 4.  P R O T O C O L D E VI A TI O N S  ..................................................................................................5 1  
1 5.  D E VI C E A C C O U N T A BI LI T Y F O R P R O D U C T S L A B E L L E D IN V E S TI G A TI O N A L  ..................5 1  
 De vice Acc o u nt a bilit y f or t he C o ntr ol De vice  ....................................................5 2  
1 6.  C O M P LI A N C E  ....................................................................................................................5 3  
 St ate me nt of C o m pli a nce  ......................................................................................5 3  
 I n vesti g at or Res p o nsi bilities ................................................................................5 3  
1 6. 2. 1.  Dele gati o n of Res p o nsi bilit y  ....................................................................5 5  
 I nstit uti o n al Re vie w B o ar d/ Et hics C o m mittee ..................................................5 5  
 S p o ns or Res p o nsi bilities  .......................................................................................5 6  
 I ns ur a nce ................................................................................................................5 6  
1 7.  M
O NI T O RI N G  ....................................................................................................................5 6  
1 8.  P O T E N TI A L R I S K S A N D B E N E FI T S  ...................................................................................5 6  
 A ntici p ate d A d verse E ve nts  .................................................................................5 6  
 A ntici p ate d A d verse De vice Effects  .....................................................................5 7  
 Ris ks Ass oci ate d wit h t he St u d y De vice(s)  ..........................................................5 8  
 Ris ks ass oci ate d wit h P artici p ati o n i n t he Cli nic al St u d y  .................................5 9  
 Ris k Mi ni miz ati o n Acti o ns  ...................................................................................5 9  
 A ntici p ate d Be nefits  ..............................................................................................5 9  
 Ris k t o Be nefit R ati o n ale  ......................................................................................6 0  
1 9.  S A F E T Y R E P O R TI N G  .........................................................................................................6 0  
 Re p ort a ble E ve nts b y i n vesti g ati o n al site t o B ost o n Scie ntific .........................6 0  

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 1 5  of 9 0  
  
 Defi niti o ns a n d Cl assific ati o n  ...............................................................................6 1  
 Rel ati o ns hi p t o St u d y De vice(s) a n d/ or St u d y Pr oce d ure  ..................................6 3  
 I n vesti g at or Re p orti n g Re q uire me nts .................................................................6 5  
 De vice Deficie ncies  ................................................................................................6 6  
 Re p orti n g t o Re g ul at or y A ut h orities / I R Bs / E Cs / R E Bs/ I n vesti g at ors  .......6 7  
2 0.  IN F O R M E D C O N S E N T  ........................................................................................................6 7  
2 1.  C O M MI T T E E S  ...................................................................................................................6 8  
 S afet y M o nit ori n g Pr ocess  ....................................................................................6 8  
 Cli nic al E ve nts C o m mittee ( C E C)  .......................................................................6 8  
 Steeri n g C o m mittee  ...............................................................................................6 9  
 D at a M o nit ori n g C o m mittee ( D M C)  ...................................................................6 9  
2 2.  S U S P E N SI O N O R T E R MI N A TI O N  ........................................................................................6 9  
2 2. 1  Pre m at ure Ter mi n ati o n of t he St u d y  ..................................................................6 9  
2 2. 1. 1  
Criteria f or Pre mat ure Ter mi nati o n of t he St u d y  ......................................6 9  
2 2. 2  Ter mi n ati o n of St u d y P artici p ati o n b y t he I n vesti g at or or Wit h dr a w al of 
I R B/ E C / R E B A p pr o v al ......................................................................................7 0  
2 2. 3. Re q uire me nts f or D oc u me nt ati o n a n d S u bject F oll o w -u p  ................................7 0  
2 2. 4  Criteri a f or S us pe n di n g/ Ter mi n ati n g a St u d y Site  ............................................7 0  
2 3.  S T U D Y R E GI S T R A TI O N A N D R E S U L T S  .............................................................................7 1  
 St u d y Re gistr ati o n  .................................................................................................7 1  
 Cli nic al I n vesti g ati o n Re p ort  ...............................................................................7 1  
 P u blic ati o n P olic y  ..................................................................................................7 1  
2 4.  B I B LI O G R A P H Y .................................................................................................................7 1  
2 5.  A B B R E VI A TI O N S A N D D E FI NI TI O N S  .................................................................................7 2  
 A b bre vi ati o ns  .........................................................................................................7 2  
 Defi niti o ns  ..............................................................................................................7 5  
 
 T a ble of Fi g ures  
Fi g ure 5 -1: A ge nt M o n orail Paclita xel -C oate d P T C A Ball o o n Cat heter  ............................... 2 2  
Fi g ure 5 -2: C he mical str uct ure of paclita xel  .......................................................................... 2 4  
Fi g ure 5 -3: C he mical Str uct ure of Acet yltri b ut yl Citrate ( A T B C)  ......................................... 2 5  

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 1 6  of 9 0  
  
Fi g ure 5 -4: C alc ul ati o n of C o ate d B all o o n S urf ace Are a  .................................................. 2 5  
Fi g ure 7 -1: A G E N T I D E St u d y Desi g n  .................................................................................. 2 9  
 
 T a ble of T a bles  
Ta ble 4. 2 -1: 6 M o nt h Res ults –  I n Ste nt Late L u me n L oss .................................................... 1 9  
Ta ble 4. 2 -2: Cli nical E n d p oi nts t hr o u g h 3 Years  ................................................................... 1 9  
Ta ble 5. 1 -1: De vice C o m p o ne nt S pecificati o ns  ..................................................................... 2 3  
Ta ble 5. 1 -2: A ge nt I D E Matri x  ............................................................................................... 2 3  
T a ble 5. 2 -1: N o mi n al Dr u g C o nte nt per B all o o n Size f or A ge nt  ...................................... 2 6  
Ta ble 8. 2 -1: I ncl usi o n Criteria  ................................................................................................ 3 3  
Ta ble 8. 3 -1: E xcl usi o n Criteria  ............................................................................................... 3 3  
Ta ble 1 0. 1 -1: Data C ollecti o n Sc he d ule  ................................................................................. 3 7  
Ta ble 1 0. 1 1 -1: S o urce D oc u me ntati o n Re q uire me nts  ............................................................ 4 5  
Ta ble 1 9. 2 -1: Safet y Defi niti o ns  ............................................................................................. 6 1  
Ta ble 1 9. 3 -1: Criteria f or Assessi n g Relati o ns hi p of St u d y De vice(s) or Pr oce d ure t o A d verse 
E ve nt  .................................................................................................................... 6 3  
Ta ble 1 9. 4 -1: I n vesti gat or Re p orti n g Re q uire me nts ............................................................... 6 5  
Ta ble 2 5. 1 -1: A b bre viati o ns  ................................................................................................... 7 2  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 1 7  of 9 0  
  
4.  I ntr o d ucti o n 
 B ac k gr o u n d  
T he A ge nt I D E trial is desi g ne d t o assess t he safet y a n d effecti ve ness of t he A ge nt T M  
Paclita xel C oate d P T C A B all o o n C at heter  c o m pare d t o ball o o n a n gi o plast y ( P O B A) i n 
patie nts wit h i n-ste nt reste n osis of a pre vi o usl y treate d lesi o n of u p t o 2 6  m m i n le n gt h ( b y 
vis ual esti mate) i n a nati ve c or o nar y arter y 2. 0 m m t o 4. 0 m m i n dia meter .  A d diti o nal 
a n gi o gra p hic a n d cli nical data was c ollecte d o utsi de of t he U S i n t he A G E N T I S R st u d y t o 
s u p p ort f ut ure F D A a p pr o val. 
C or o nar y arter y disease ( C A D) is c haracterize d b y at her oscler osis i n t he e picar dial c or o nar y 
arteries. At her oscler otic pla q ues, t he hall mar k of at her oscler osis, pr o gressi vel y narr o w t he 
c or o nar y arter y l u me n a n d i m pair a nte gra de m y ocar dial bl o o d fl o w. T he re d ucti o n i n 
c or o nar y arter y fl o w ma y be s y m pt o matic or as y m pt o matic, occ ur wit h e xerti o n or at rest, 
a n d c ul mi nate i n a m y ocar dial i nfarcti o n, de pe n di n g o n o bstr ucti o n se verit y a n d t he ra pi dit y 
of de vel o p me nt.  
S u bjects wit h c or o nar y arter y disease ha ve t hree c o m m o n t hera pe utic o pti o ns 1) me dical 
t hera p y a n d ris k fact or m o dificati o n, 2) c or o nar y arter y b y pass graft s ur ger y ( C A B G), a n d 3) 
perc uta ne o us c or o nar y i nter ve nti o n ( P CI). As P CI tec h n ol o g y a n d re vasc ulariz ati o n 
pr oce d ures e v ol ve d, ball o o n a n gi o plast y, bare metal ste nt ( B M S) a n d dr u g -el uti n g ste nt 
( D E S) s uccee de d eac h ot her as t he pri mar y cat heter-base d treat me nts f or c or o nar y arter y 
disease.  
Reste n osis, t he re narr o wi n g of a bl o o d vessel t hat ha d bec o me narr o we d a n d recei ve d 
treat me nt, is a c o m m o n a d verse e ve nt of e n d o vasc ular pr oce d ures s uc h as a n gi o plast y a n d 
ste nti n g.  Ma na ge me nt of i n -ste nt reste n osis (I S R) f oll o wi n g i m pla ntati o n of a c or o nar y ste nt 
is cli nicall y c halle n gi n g. C urre ntl y a vaila ble t hera pe utic o pti o ns i ncl u de dr u g -c oate d ball o o ns 
( D C B) c oate d wit h a n a nti pr oliferati ve dr u g paclita xel t hat i n hi bits t he pr oliferati o n of 
ne oi nti mal s m o ot h m uscle cells, t here b y re d uci n g t he rate of  reste n osis.1 Data fr o m n u mer o us 
cli nical trials a n d re gistries ha ve de m o nstrate d t he use of dr u g c oate d ball o o ns ( D C B) as a 
safe a n d effecti ve treat me nt f or I S R.2 T he Ger ma n c o nse ns us gr o u p rec o m me n ds D C B 
treat me nt n ot o nl y f or I S R, b ut als o f or de-n o v o lesi o ns i n s mall c or o nar y arteries a n d 
bif urcati o n lesi o ns .3 Si milarl y, t he G ui da nce o n M y ocar dial Re vasc ularizati o n release d b y 
t he E ur o pea n S ociet y of Car di ol o g y ( E S C) a n d t he E ur o pea n Ass ociati o n f or Car di o-
T h oracic S ur ger y ( E A C T S) rec o m me n ds D C B treat me nt as a n alter nati ve o pti o n t o treat 
I S R.4 
A ge nt  D C B is a p aclita xel -coate d  Perc uta ne o us Tra nsl u mi nal C or o nar y A n gi o plast y ( P T C A) 
de vice base d o n t he well c haracterize d a n d c o m merciall y a vaila ble E mer ge ™ P T C A 
Dilatati o n Cat heter ( B ost o n Scie ntific C or p orati o n, Massac h usetts, U nite d States).  
C olla b orati ve eff orts bet wee n B ost o n Scie ntific a n d He m ote q A G ( W uersele n, Ger ma n y) 
res ulte d i n t he de vel o p me nt of a l o w-d ose f or m ulati o n of paclita xel ( 2 m/ m m 2) ble n de d 
wit h t he i nacti ve e xci pie nt Acet yl Tri b ut yl Citrate ( A T B C).  T his paclita xel c oati n g, o nce 
deli vere d t o t he arterial tiss ue, is t h o u g ht t o mai ntai n t he l u mi nal dia meter b y re d uci n g 
ne oi nti mal pr oliferati o n a n d t he o nset of reste n osis.  T he A ge nt de vice i nc or p orates a n u m ber 
of feat ures desi g ne d t o all o w a re d uce d paclita xel d ose de nsit y ( 2 m/ m m 2) as c o m pare d t o 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 1 8  of 9 0  
  
t he maj orit y of c urre ntl y mar kete d pr o d ucts, s uc h as Se Q ue nt Please D C B ( 3 m/ m m
2) (B. 
Bra u n I nter ve nti o nal S yste ms I nc.) . I n precli nical st u dies, t he A ge nt D C B de m o nstrate d 
c o m para ble tiss ue dr u g a bs or pti o n, cli nical safet y a n d vasc ular res p o nse o utc o mes t o 3 
m/ m m 2 f or m ulati o ns of C E-mar ke d D C B platf or ms, w hile re d uci n g s yste mic dr u g 
e x p os ure. T he A ge nt I S R st u d y c o m pare d a re d uce d dr u g c oati n g f or m ulati o n wit h t he 
Se Q ue nt Please D C B. A ge nt pr o ve d n o n -i nferi or t o Se Q ue nt Please f or i n-ste nt late l oss at 6 
m o nt hs. Deat h a n d MI were si milar bet wee n gr o u ps at 1 2 m o nt hs; t he rate of ste nt 
t hr o m b osis ( S T) was  n u mericall y l o wer w it h A ge nt ( n o S T e ve nts re p orte d i n t he A ge nt ar m 
o ut t o 1 2 M) b ut di d n ot reac h si g nifica nce . 
 
Data fr o m t his A G E N T I D E st u d y will c haracterize t he cli nical safet y a n d efficac y  of dr u g 
c oate d ball o o n c o m pare d wit h c o n ve nti o nal ball o o n a n gi o plast y f or treat me nt of c or o nar y i n-
ste nt reste n osis. 
 Cli nic al B ac k gr o u n d   
D ata fr o m a pr os pe cti ve E ur o pea n ra n d o mize d trial , AG E N T I S R, t o de m o nstrate safet y a n d 
perf or ma nce of t he A ge nt Paclita xel -C oate d P T C A Ball o o n Cat heter w he n c o m pare d t o t he 
Se Q ue nt Please Paclita xel -Releasi n g C or o nar y Ball o o n Cat heter i n t he treat me nt of i n -ste nt 
reste n osis is pr o vi de d  bel o w.  A s u m mar y of t he I S A R -D E SI R E 3 A cli nical trial is als o 
pr o vi de d.  T his cli nical data i n c o m bi nati o n wit h ot her precli nical a n d cli nical data s u p p orts 
t he safet y a n d perf or ma nce  of A ge nt f or t he treat me nt of patie nts wit h I S R.  
4. 2. 1.  A G E N T I S R Pr os pecti ve R a n d o mize d Tri al  
T he A G E N T I S R cli nical st u d y  was  a pr os pecti ve, m ultice nter, 1: 1 ra n d o mize d, n o n -
i nferi orit y st u d y c o n d ucte d at 1 1  sites i n Ger ma n y a n d Fra nce. T he st u d y’s o bjecti ve was  t o 
deter mi ne safet y a n d perf or ma nce of A ge nt Paclita xel -C oate d P T C A Ball o o n Cat heter 
c o m pare d t o t he Se Q ue nt Please Paclita xel -Releasi n g C or o nar y Ball o o n Cat heter f or t he 
treat me nt of patie nts wit h i n-ste nt reste n osis of t he pre vi o usl y treate d lesi o n. T he trial 
e nr olle d 1 2 5 patie nts wit h e nr oll me nt c o m plete d o n Ma y 1 1 , 2 0 1 6; 6 -m o nt h a n d 1 2 -m o nt h 
i nteri m res ults a n d cli nical e n d p oi nts t hr o u g h 3 years of f oll o w -u p are a vaila ble . T he pri mar y 
e n d p oi nt of t his st u d y was  i n-ste nt late l u me n l oss ( L L L) at 6 m o nt hs p ost pr oce d ure as 
meas ure d b y q ua ntitati ve c or o nar y a n gi o gra p h y a n d  is p o were d t o test f or n o n-i nferi orit y of 
t he A ge nt ball o o n t o t he Se Q ue nt Please ball o o n. Cli nical e n d p oi nts meas ure d i n-h os pital , at 
3 0 da ys , a n d t he n at 6 m o nt hs, 1 year, 2 years a n d 3 years i ncl u de:  
• 
T L R rate  
• 
T V R rate  
• 
All deat h rate  
• 
Car diac deat h rate  
• 
N o n -car diac deat h rate  
• 
MI rate  
• 
C o m p osite of all deat h a n d MI  
• 
Q W MI rate a n d N Q W MI rate  
• 
Ste nt t hr o m b osis rate  
• 
T L F rate  
• 
T V F rate  

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
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Pa ge 2 0  of 9 0  
  
E ve nts  
A ge nt   
Se Q ue nt Ple ase   
P  v al ue  
MI  
1. 5 % ( 1/ 6 5)   
1. 7 % ( 1/ 6 0)   
1. 0 0  
Q -wa ve MI  
0. 0 % ( 0/ 6 5)   
0. 0 % ( 0/ 6 0)   
1. 0 0  
N o n -Q -wa ve MI  
1. 5 % ( 1/ 6 5)   
1. 7 % ( 1/ 6 0)   
1. 0 0  
T L R  
3. 1 % ( 2/ 6 5)   
5. 0 % ( 3/ 6 0)   
0. 9 3  
T V R  
4. 6 % ( 3/ 6 5)   
5. 0 % ( 3/ 6 0)   
1. 0 0  
T L F  
6. 2 % ( 4/ 6 5)   
6. 7 % ( 4/ 6 0)   
0. 9 0  
T V F  
7. 7 % ( 5/ 6 5)   
6. 7 % ( 4/ 6 0)   
1. 0 0  
Ste nt T hr o m b osis  
0. 0 % ( 0/ 6 5)   
1. 7 % ( 1/ 6 0)   
0. 9 7  
1 -ye ar  
 
 
 
Deat h a n d MI  
6. 2 % ( 4/ 6 5)   
5. 0 % ( 3/ 6 0)   
1. 0 0  
Deat h  
3. 1 % ( 2/ 6 5)   
1. 7 % ( 1/ 6 0)   
1. 0 0  
Car diac Deat h  
3. 1 % ( 2/ 6 5)   
1. 7 % ( 1/ 6 0)   
1. 0 0  
N o n -Car diac Deat h  
0. 0 % ( 0/ 6 5)   
0 % ( 0/ 6 0)   
1. 0 0  
MI  
4. 6 % ( 3/ 6 5)   
3. 3 % ( 2/ 6 0)   
1. 0 0  
Q -wa ve MI  
0. 0 % ( 0/ 6 5)   
0. 0 % ( 0/ 6 0)   
1. 0 0  
N o n -Q -wa ve MI  
4. 6 % ( 3/ 6 5)   
3. 3 % ( 2/ 6 0)   
1. 0 0  
T L R  
7. 7 % ( 5/ 6 5)   
1 0. 0 % ( 6/ 6 0)   
0. 8 9  
T V R  
1 0. 8 % ( 7/ 6 5)    
1 1. 7 % ( 7/ 6 0)   
1. 0 0  
T L F  
1 0. 8 % ( 7/ 6 5)   
1 1. 7 % ( 7/ 6 0)   
1. 0 0  
T V F  
1 3. 8 % ( 9/ 6 5)   
1 3. 3 % ( 8/ 6 0)   
1. 0 0  
Ste nt T hr o m b osis  
0. 0 % ( 0/ 6 5)   
3. 3 % ( 2/ 6 0)   
0. 4 4  
2 ye ars  
 
 
 
Deat h a n d MI  
9. 2 % ( 6/ 6 5)   
1 0 % ( 6/ 6 0)   
1. 0 0  
Deat h  
6. 2 % ( 4/ 6 5)   
3. 3 % ( 2/ 6 0)   
0. 7 5  
Car diac Deat h  
4. 6 % ( 3/ 6 5)   
3. 3 % ( 2/ 6 0)   
1. 0 0  
N o n -Car diac Deat h  
1. 5 % ( 1/ 6 5)   
0 % ( 0/ 6 0)   
1. 0 0  
MI  
6. 2 % ( 4/ 6 5)   
6. 7 % ( 4/ 6 0)   
1. 0 0  
Q -wa ve MI  
1. 5 % ( 1/ 6 5)   
0 % ( 0/ 6 0)   
1. 0 0  
N o n -Q -wa ve MI  
6. 2 % ( 4/ 6 5)   
6. 7 % ( 4/ 6 0)   
1. 0 0  
T L R  
1 0. 8 % ( 7/ 6 5)   
1 5. 0 % ( 9/ 6 0)   
0. 6 6  
T V R  
1 3. 8 % ( 9/ 6 5)   
1 6. 7 % ( 1 0/ 6 0)   
0. 8 5  
T L F  
1 3. 8 % ( 9/ 6 5)   
1 6. 7 % ( 1 0/ 6 0)   
0. 8 5  
T V F  
1 6. 9 % ( 1 1/ 6 5)   
1 8. 3 % ( 1 1/ 6 0)   
1. 0 0  
Ste nt T hr o m b osis  
0 % ( 0/ 6 5)   
6. 7 % ( 4/ 6 0)   
0. 1 1  
3 -ye ar  
 
 
 
Deat h a n d MI  
1 6. 9 % ( 1 1/ 6 5)   
1 3. 3 % ( 8/ 6 0)   
0. 7 6  
Deat h  
1 3. 8 % ( 9/ 6 5)   
5. 0 % ( 3/ 6 0)   
0. 1 7  
Car diac Deat h  
7. 7 % ( 5/ 6 5)   
3. 3 % ( 2/ 6 0)   
0. 5 0  
N o n -Car diac Deat h  
6. 2 % ( 4/ 6 5)   
1. 7 % ( 1/ 6 0)   
0. 4 1  
MI  
6. 2 % ( 4/ 6 5)   
8. 3 % ( 5/ 6 0)   
0. 9 0  
Q -wa ve MI  
1. 5 % ( 1/ 6 5)   
0 % ( 0/ 6 0)   
1. 0 0  
N o n -Q -wa ve MI  
6. 2 % ( 4/ 6 5)   
8. 3 % ( 5/ 6 0)   
0. 9 0  
T L R  
1 2. 3 % ( 8/ 6 5)   
1 5 % ( 9/ 6 0)   
0. 8 6  

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Pa ge 2 1  of 9 0  
  
E ve nts  
A ge nt   
Se Q ue nt Ple ase   
P  v al ue  
T V R  
1 6. 9 % ( 1 1/ 6 5)   
1 6. 7 % ( 1 0/ 6 0)   
1. 0 0  
T L F  
1 8. 5 % ( 1 2/ 6 5)   
1 6. 7 % ( 1 0/ 6 0)   
0. 9 8  
T V F  
2 1. 5 % ( 1 4/ 6 5)   
1 8. 3 % ( 1 1/ 6 0)   
0. 8 2  
Ste nt T hr o m b osis  
0 % ( 0/ 6 5)   
8. 3 % ( 5/ 6 0)   
0. 0 6  
 
N u m bers are % (c o u nt/s a m ple size) 
P v al ues are fr o m K -S test f or i nterv al -sc ale d v ari a bles a n d t he χ 2 or K -W test f or ot her v ari a bles  
A b brevi ati o n MI = my oc ar di al i nf arcti o n; T L R =t ar get lesi o n rev asc ul ariz ati o n ( by defi niti o n T L R is 
als o a T V R); T V R =t ar get vessel rev asc ul ariz ati o n; T L F =t ar get lesi o n f ail ure ( defi ne d as c o m p osite 
of c ar di ac de at h, MI a n d T L R)  
 
I n c o ncl usi o n, t his st u d y met its pri mar y o bjecti ve b y de m o nstrati n g n o n-i nferi orit y of t he 
A ge nt D C B t o Se Q ue nt Please wit h res pect t o t he 6 -m o nt h  a n gi o gra p hic e n d p oi nt of i n -ste nt 
L L L  ( 0. 0 4 6).  Cli nical e ve nts rates were c o m para ble i n b ot h gr o u ps t hr o u g h 3 years of 
f oll o w-u p. I m p orta ntl y, n o ste nt t hr o m b osis was re p orte d i n t he A ge nt gr o u p t hr o u g h 3 years . 
T he I S A R -D E SI R E 3 A trial was a pr os pecti ve, m ultice nter, n o n -ra n d o mize d, si n gle ar m st u d y 
of A ge nt D C B  wit h c o m paris o n a gai nst a n hist orical c o ntr ol gr o u p ( Se Q ue nt Please D C B) 
fr o m t he I S A R-D E SI R E 3 trial f or t he treat me nt of s u bjects wit h a c or o nar y reste n osis after 
i m pla ntati o n of li m us-a nal o g ue dr u g -el uti n g ste nts ( D E S). T he trial e nr olle d 1 2 5 patie nts . The 
pri mar y e n d p oi nt was I n -se g me nt perce nt dia meter ste n osis ( % D S) c ollecte d d uri n g  f oll o w-u p 
a n gi o gra p h y  at 6-8 m o nt hs p ost i n de x pr oce d ure. T he A ge nt D C B was s h o w n t o be n o n -
i nferi or t o t he Se Q ue nt Please D C B f or t he pri mar y e n d p oi nt (I n-se g me nt perce nt dia meter 
ste n osis). T he % D S f or t he A ge nt D C B gr o u p was 3 8. 9 ± 1 7. 5 % a n d t he % D S f or t he Se Q ue nt 
Please D C B gr o u p was 3 8. 0 ± 2 1. 5 % ( P = 0. 0 0 5 6). T L R i n t he A ge nt D C B gr o u p a n d Se Q ue nt 
Please D C B gr o u p at 1 year was 2 0. 6 % a n d 2 2. 1 %, res pecti vel y ( P = 0. 8 0) .   All -ca use m ortalit y 
i n t he A ge nt D C B gr o u p a n d Se Q ue nt Please D C B gr o u p at 1 year p ost i n de x pr oce d ure  was 
0. 8 % a n d 2. 2 %, res pecti vel y ( P = 0. 3 9). T he i nci de nce of e ve nts di d n ot differ bet wee n t he 
A ge nt D C B a n d Se Q ue nt Please D C B gr o u ps. 5 
A ge nt paclita xel -c oate d ball o o n was gra nte d a C E mar k i n J ul y 2 0 1 4 a n d is c urre ntl y 
mar kete d i n E ur o pe a n d ot her re gi o ns wit h i n dicati o ns f or perc uta ne o us tra nsl u mi nal 
c or o nar y a n gi o plast y ( P T C A) f or treat me nt of i n-ste nt reste n osis (I S R) a n d de n o v o s mall 
vessel disease . 
 St u dy R ati o n ale  
D r u g C oate d B all o o n tec h n ol o g y ca n be a n alter nati ve t hera p y a vaila ble f or U S car di ol o gists 
t o treat patie nts wit h i n -ste nt reste n osis i n c or o nar y vessels. As n ote d i n secti o n 4. 2  cli nical 
data are a vaila ble fr o m t he ra n d o mize d trial wit h t he A ge nt pr o d uct, A G E N T I S R. T he data 
fr o m t his R C T c o u ple d wit h data fr o m t his ra n d o mize d I D E st u d y are e x pecte d t o  pr o vi de 
a de q uate e vi de nce s u p p orti n g t he safet y a n d efficac y f or t he A ge nt D C B pr o d uct f or use i n 
t he U S. W hile t he c o ntr ol ar m i n t he A G E N T I S R st u d y is a n ot her D C B t hat is n ot a p pr o ve d 
i n t he U nite d States, t he c o ntr ol D C B has bee n s h o w n t o be s u peri or t o P O B A w hic h is a n 
acce pte d t hera p y f or I S R i n t he U nite d States. T he direct s u peri orit y of A ge nt o ver P O B A is 
t he h y p ot hesis t hat will be pr o ve n i n t his ra n d o mize d I D E st u d y. P O B A is a wi del y use d 

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Pa ge 2 2  of 9 0  
  
treat me nt f or I S R, as t he 2 0 1 1 A C C F/ A H A/ S C AI G ui deli ne f or Perc uta ne o us C or o nar y 
I nter ve nti o n ( Le vi ne, et al), secti o n 6. 3. 4 rec o m me n ds use of P O B A t o treat f ocal reste n osis 
after D E S i m pla ntati o n .    
A 1 2 -m o nt h pri mar y e n d p oi nt  will be e val uate d as t his is after t he dr u g has bee n s h o w n t o 
ha ve left t he a d ve ntitia, gi ve n t he release ki netics.  
5.  De vice Descri pti o n  
T he A ge nt Paclita xel -C oate d P T C A Ball o o n Cat heter ( A ge nt D C B) is a M o n orail 
Perc uta ne o us Tra nsl u mi nal C or o nar y A n gi o plast y ( P T C A) ball o o n cat heter wit h a se mi -
c o m plia nt ball o o n c oate d wit h a f or m ulati o n of paclita xel ( dr u g) a n d a n e xci pie nt, Acet yl -
Tri -n -b ut yl citrate ( A T B C). T he ball o o n cat heter platf or m is base d o n t he c o mmerciall y 
a vaila ble B S C  E mer ge ™ P T C A ball o o n cat heter s yste m ( K 1 3 0 3 9 1). T he A ge nt ball o o n 
cat heter is desi g ne d t o i n hi bit vasc ular reste n osis b y deli veri n g dr u g t o disease d arterial 
tiss ue. 
T he cat heter has a dr u g c oati n g f or m ulati o n c o nsisti n g of paclita xel (acti ve p har mace utical 
i n gre die nt) at 2 µ g/ m m 2, a n d A T B C e xci pie nt (i nacti ve i n gre die nt).   
 
  
Fi g ure 5 -1 : A ge nt M o n or ail P aclit a xel-C o ate d P T C A B all o o n C at heter  
 Device C o m p o ne nt Descri pti o n  
T he de vice c o m p o ne nt of A ge nt is t he E mer ge M o n orail P T C A ball o o n cat heter s yste m.  
A ge nt a n d E mer ge are hi g hl y si milar t o t he pre dicate de vice, A pe x P T C A ball o o n cat heter 
( B ost o n Scie ntific C or p orati o n). 
 
 
 
 
 
 
 
 
 
 
 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
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Pa ge 2 4  of 9 0  
  
 Dr u g C o m p o ne nt Descri pti o n a n d C o ati n g F or m ul ati o n  
T he ball o o n c oati n g c o nsists of paclita xel ( P T x) a n d t he e xci pie nt, Acet yl -Tri -n -B ut yl Citrate  
( A T B C). Paclita xel ( P T x) is t he acti ve p har mace utical i n gre die nt o n t he A ge nt D C B. 
Paclita xel is a w hite p o w der, is olate d fr o m a s pectr u m of T A X U S s pecies a n d h y bri ds. It is a 
ter pe n oi d wit h a c haracteristic ta xa ne s kelet o n of 2 0 car b o n at o ms, a m olec ular wei g ht of 
8 5 3. 9 1 g/ m ol,  a n d a m olec ular f or m ula of C 4 7H 5 1N O 1 4. It is hi g hl y li p o p hilic a n d i ns ol u ble i n 
water, b ut is freel y s ol u ble i n met ha n ol, et ha n ol, c hl or of or m, et h yl acetate, a n d di met h yl 
s ulf o xi de.7, 8 T he c he mical str uct ure of paclita xel is pr o vi de d i n Fi g ure 5 -2 . 
Paclita xel is a n a nti pr oliferati ve dr u g t hat i n d uces irre versi ble p ol y merizati o n of cell 
micr ot u b ules, t h us i n hi biti n g mit osis. It is wi del y use d i n a nti ne o plastic c he m ot hera p y of 
ca ncers; h o we ver, d oses re q uire d i n c he m ot hera pe utic treat me nt are si g nifica ntl y hi g her per 
treat me nt c ycle i n ca ncer patie nts t ha n i n c or o nar y arter y disease patie nts.8 Paclita xel has 
bee n s h o w n t o i n hi bit pr oliferati o n a n d mi grati o n of s m o ot h m uscle cells, effecti vel y 
s u p pressi n g ne oi nti mal h y per plasia after vessel i nj ur y. 8 -1 0 
 
 
 
 
 
 
Fi g ure 5 -2 : C he mic al str uct ure of p aclit a xel  
 
T he c oati n g utilizes t he i nacti ve i n gre die nt Acet yl -Tri -n -B ut yl Citrate ( A T B C) as a n 
e xci pie nt t o facilitate t he release a n d tra nsfer of paclita xel i nt o t he arterial wall. A T B C is a 
car b o x ylic aci d ester wit h a m olec ular wei g ht of 4 0 2. 4 8 g/ m ol. A T B C is a c ol orless, sli g htl y 
visc o us li q ui d wit h ver y fai nt s weet her bace o us o d or. T he c he mical str uct ure of A T B C is 
pr o vi de d i n Fi g ure 5 -3 . 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
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Pa ge 2 5  of 9 0  
  
 
Fi g ure 5 -3 : C he mic al Str uct ure of Acet yltri b ut yl Citr ate ( A T B C) 
  
  
 
 
 
  
 
  
 
 
 
  
 
  
 
  
 
  
  
 
 
 
 
 
 
 
 
 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
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Pa ge 2 7  of 9 0  
  
i n c or o nar y arteries. T he res ults of P K st u dies I M T R 2 0 1 1 1 2 4 5 a n d 0 9-1 0 7 N s u p p ort t he l ocal 
a n d s yste mic safet y of A ge nt  a n d are o n file at B S C . 
 Device L a beli n g  
T he Directi o ns f or Use ( D F U) will be i ncl u de d i n t he A G E N T I D E st u d y Ma n ual of 
O perati o ns.  T he st u d y de vices are la bele d o n t he fr o nt, a n d si de of t he o uter cart o n a n d o n 
t he i nsi de sterile p o uc h.  Pac ka gi n g will i ncl u de peela ble, self-a d hesi ve la bels f or eac h u nit of 
pr o d uct s hi p pe d.  T he la beli n g will i ncl u de t he f oll o wi n g i nf or mati o n:  
•  Pr o d uct Na me  
•  Catal o g N u m ber a n d U ni versal Part N u m ber ( U P N)  
•  Gl o bal Tra de Ite m N u m ber ( G TI N)  
•  L ot n u m ber  
•  Ball o o n  di me nsi o ns ( ball o o n dia meter a n d ball o o n  le n gt h i n m m) 
•  E x pirati o n ( use b y) date  
T he f oll o wi n g state me nts a p pear o n t he A G E N T st u d y de vice pr o d uct la beli n g f or cli nical 
U S distri b uti o n.  
C a uti o n: I n vesti g ati o n al De vice.  Li mite d b y U nite d St ates l a w t o i n vesti g ati o n al use.  
E xcl usi vel y f or Cli nic al I n vesti g ati o ns  
6.  St u d y O bjecti ves  a n d E n d p oi nts  
T o assess t he safet y a n d effecti ve ness of t he A ge nt T M  Paclita xel C oate d P T C A Ball o o n 
Cat heter c o m pare d t o ball o o n a n gi o plast y ( P O B A) i n patie nts wit h i n -ste nt reste n osis of a 
pre vi o usl y treate d lesi o n of u p t o 2 6  m m i n le n gt h ( b y vis ual esti mate) i n a nati ve c or o nar y 
arter y 2. 0 m m t o 4. 0 m m i n dia meter.  
 Pri m ary E n d p oi nt  
T he pri mar y e n d p oi nt is  t he 1 2 -m o nt h  Tar get Lesi o n Fail ure ( T L F) rate, defi ne d as a n y 
isc he mia-dri ve n re vasc ularizati o n of t he tar get lesi o n ( T L R), m y ocar dial i nfarcti o n ( MI, Q -
wa ve a n d n o n – Q -wa ve) relate d t o t he tar get vessel, or car diac deat h.  T he MI e ve nts i ncl u de 
t he P P MI acc or di n g t o t he S C AI MI defi niti o n a n d t he s p o nta ne o us MI acc or di n g t o t he 4 t h 
U ni versal MI defi niti o n.  
 
 A d diti o n al E n d p oi nts  
Cli nical e n d p oi nts meas ure d i n -h os pital a n d at 3 0  da ys, 6  m o nt hs, 1 2 m o nt hs, t he n a n n uall y 
t hr o u g h 5 years.  
• 
T ar get lesi o n re vasc ularizati o n ( T L R) rate, Tar get lesi o n fail ure ( T L F) rate ( pri mar y 
e n d p oi nt at 1 2 m o nt hs), Tar get vessel re vasc ularizati o n ( T V R) rate  
• 
Tar get vessel fail ure ( T V F) rate  

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 2 8  of 9 0  
  
• 
MI ( Q -wa ve a n d n o n – Q -wa ve) rate  (P P MI per t he S C AI defi niti o n a n d s p o nta ne o us 
MI per 4
t h U ni versal defi niti o n)  
• 
Car diac deat h  rate  
• 
N o n -car diac deat h  rate 
• 
All -ca use deat h rate  
• 
Ste nt t hr o m b osis rates ( per  Aca de mic Researc h C o ns orti u m [ A R C] defi niti o ns)  
Peri pr oce d ural e n d p oi nt:  
• 
Cli nical pr oce d ural s uccess rate  
• 
Tec h nical s uccess rate  
 
C ha n ge i n Q ualit y of Life:  
• 
F u ncti o nal stat us of ge neral healt h -relate d q ualit y of life meas ure d b y c ha n ges i n E Q-
5 D sc ores at h os pital disc har ge, 1 2 m o nt hs, 2 4 m o nt hs a n d 3 6 m o nt hs  
7.  St u d y Desi g n  
T he A G E N T I D E cli nical trial is a pr os pecti ve, m ulti -ce nter, 2: 1 ra n d o mize d ( A G E N T t o 
P O B A), c o ntr olle d, si n gle -bli n d, s u peri orit y trial t o assess t he safet y a n d effecti ve ness of t he 
A G E N T D C B i n patie nts wit h i n-ste nt reste n osis.  
 Sc ale a n d D ur ati o n  
T he A G E N T  St u d y will be c o n d ucte d at u p t o 4 0  sites i n t he U nite d States w it h pla n ne d 
i nitial e nr oll me nt of  at least  4 8 0  s u bjects.  A n i nteri m a nal ysis f or t he sa m ple size re-
esti mati o n will be perf or me d o n t he 1 -year data fr o m t he first 4 0 % ( 1 9 2) ra n d o mize d s u bjects 
of t he i nitial e nr oll me nt of 4 8 0 patie nts. T he fi nal sa m ple size ma y be i ncrease d u p t o a 
ma xi m u m of 6 0 0 s u bjects e nr olle d i n t he trial . 
All s u bjects will be scree ne d acc or di n g t o t he pr ot oc ol i ncl usi o n a n d e xcl usi o n criteria.   
S u bjects meeti n g all i ncl usi o n criteria a n d n o e xcl usi o n criteria will be ra n d o mize d i n a 2: 1 
all ocati o n t o eit her A G E N T D C B or P O B A, res pecti vel y.  
Cli nical f oll o w -u p will be re q uire d at t he f oll o wi n g ti me p oi nts: i n h os pital, 3 0 da ys, 6  
m o nt hs, 1 2 m o nt hs , a n d a n n uall y t hr o u g h 5  years  p ost i n de x pr oce d ure.  
A sc he matic of t he A G E N T I D E  trial desi g n is s h o w n i n t he dia gra m bel o w i n Fi g ure 7 -1 .   

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 2 9  of 9 0  
  
 
Fi g ure 7 -1 : A G E N T I D E St u d y Desi g n  
 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 3 0  of 9 0  
  
 Tre at me nt Assi g n me nt  
O nce t he s u bject has met all cli nical i ncl usi o n a n d n o cli nical e xcl usi o n criteria, t he s u bject 
s h o ul d be c o nsi dere d eli gi ble t o be e nr olle d i n t he trial.  If t he s u bject is f o u n d t o meet 
e xcl usi o n criteria d uri n g t he a n gi o gra p hic eli gi bilit y assess me nt, t he s u bject will be 
c o nsi dere d a scree n fail ure. If t he s u bject is f o u n d t o meet t he i ncl usi o n criteria d uri n g t he 
a n gi o gra p hic p hase of t he pr oce d ure, t he s u bject will be c o nsi dere d eli gi ble t o be e nr olle d.  
Eli gi ble s u bjects i n t his trial will  be ra n d o mize d i n a 2: 1 all ocati o n t o eit her A G E N T T M or 
P O B A  a n d stratifie d b y ce nter a n d si n gle vers us m ulti ple ste nt la yer reste n osis. After 
s uccessf ul pre-treat me nt of t he lesi o n a n d c o nfir mati o n t hat i ncl usi o n/ e xcl usi o n criteria ha ve 
bee n met, s u bjects will be ra n d o mize d ( 2: 1) t o recei ve eit her t he test de vice or a c o ntr ol 
de vice.  A s u bject will be c o nsi dere d e nr olle d at t he ti me of r a n d o mizati o n.  All ra n d o mize d 
s u bjects will be assi g ne d u ni q ue i de ntificati o n n u m be rs. Me di data Ra ve E D C s yste m will be 
use d t o assi g n s u bjects t o t he treat me nt gr o u ps/ de vice.  I nstr ucti o ns o n ra n d o mizati o n a n d t he 
Me di data Ra ve E D C s yste m are pr o vi de d i n t he Ma n ual of O perati o ns  
If a s u bject is ra n d o mize d t o P O B A a n d prese nts d uri n g f oll o w -u p wit h s y m pt o matic a n d 
a n gi o gra p hicall y se vere reste n osis ( meets criteria f or isc he mia -dri ve n re vasc ularizati o n) 
wit hi n 1 2 m o nt hs of e nr oll me nt, t he s u bject will be eli gi ble t o cr oss o ver a n d recei ve a n 
A ge nt de vice . T he A ge nt D C B is a n i n vesti gati o nal de vice a n d m ust be de pl o ye d b y st u d y 
pers o n nel (i n vesti gat or or s u b -i n vesti gat or) at t he partici pati n g site.  T here will be a 
ma xi m u m of 3 0 s u bjects  i n t he st u d y t hat will be all o we d t o cr oss o ver  a n d be treate d wit h 
t he A ge nt D C B after i nitial P O B A treat me nt . Use of t he A ge nt D C B d uri n g t he i n de x 
pr oce d ure or as part of a pla n ne d, sta ge d pr oce d ure is n ot per mitte d i n patie nts ra n d o mize d t o 
t he P O B A ar m u n der a n y circ u msta nces.   Cr oss o ver pr oce d ures will be m o nit ore d t o e ns ure 
re q uire d cli nical a n d a n gi o gra p hic criteria are met.  
A G E N T is a si n gle bli n d trial. S u bjects  will be bli n de d t o treat me nt assi g ne d a n d treat me nt 
recei ve d. All s u bjects m ust re mai n bli n de d t hr o u g h st u d y c o m pleti o n. Pac ka gi n g of t he 
i n vesti gati o nal c o ntr ol a n d test de vices are di ffere nt, t heref ore t he I n vesti gat or perf or mi n g 
t he pr oce d ure will n ot be bli n de d t o t he assi g ne d treat me nt ar m or res ulti n g treat me nt. St u d y 
site pers o n nel will be trai ne d not t o discl ose t he treat me nt assi g n me nt  t o t he s u bject t o 
mi ni mize t he p ote ntial u n bli n di n g of t he s u bject. W he n p ossi ble, t he site pers o n nel 
c o n d ucti n g cli nical f oll o w -u p will be bli n de d t o a s u bject’s treat me nt assi g n me nt . C o re 
La b orat or y pers o n nel  a n d t he Cli nical E ve nts C o m mittee ( C E C ) will be bli n de d t o a s u bject’s 
treat me nt assi g n me nt d uri n g t he trial. T he Bi ostatisticia n will re mai n bli n de d u ntil t he 
a nal ysis of res ults. I nstr ucti o ns re gar di n g t he u n bli n di n g of a s u bject f or a me dical 
e mer ge nc y ca n be f o u n d i n t he Ma n ual of O perati o ns  ( M O P). 
7. 2. 1.  T ar get a n d N o n -t ar get Lesi o ns 
A tar get lesi o n is t he lesi o n selecte d b y t he I n vesti gat or f or treat me nt wit h t he st u d y /c o ntr ol 
de vice  ( A G E N TT M or P O B A) . It is e x pecte d t hat o nl y a si n gle ball o o n cat heter  will be use d 
t o treat t he tar get lesi o n, a n d t he ball o o n s h o ul d o nl y be i nflate d o nce.  Re peat i nflati o n of t he 
D C B at t he treat me nt site s h o ul d be li mite d t o e mer ge nc y/ bail -o ut sit uati o ns, e. g. t o treat 
vessel perf orati o ns of fl o w -li miti n g dissecti o ns whe n e xc ha n ge f or a n u nc oate d ball o o n is 
dee me d i na p pr o priate d ue t o safet y c o nsi dera ti o ns.  T he tar get lesi o n i ncl u des t he arterial 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 3 1  of 9 0  
  
se g me nt treate d wit h t he st u d y/c o ntr ol de vice  pl us t he arterial se g me nt 5 m m pr o xi mal a n d 5 
m m distal t o t he treat me nt site. T he tar get lesi o n m ust meet all t he a n gi o gra p hic selecti o n 
criteria.  
U p t o 2  nati ve c or o nar y arter y lesi o ns i n 2 maj or e picar dial vessels ma y be treate d. O ne 
lesi o n m ust meet t he a n gi o gra p hic criteria descri be d a b o ve a n d is a p pr o priate t o be treate d 
wit h a n A G E N T T M  dr u g c oate d ball o o n . A ma xi m u m of 1 n o n-tar get lesi o n i n 1 n o n-tar get 
vessel ma y be treate d wit h a c o m merciall y a vaila ble de vice d uri n g t he i n de x pr oce d ure.  T he 
n o n -tar get lesi o n m ust  be treate d  d uri n g t he i n de x pr oce d ure pri or t o t he treat me nt of t he 
tar get lesi o n a n d dee me d a n a n gi o gra p hic s uccess pri or t o t he treat me nt of t he tar get lesi o n.  
N ote:  S uccessf ul treat me nt of a n o n -tar get lesi o n is defi ne d as a resi d ual ste n osis of ≤ 3 0 % 
i n 2 near-ort h o g o nal pr ojecti o ns wit h TI MI 3 fl o w, as vis uall y assesse d b y t he p h ysicia n, 
wit h o ut t he occ urre nce of pr ol o n ge d c hest pai n or E C G c ha n ges c o nsiste nt wit h MI .  
N ote : M ulti ple f ocal ste n oses will be c o nsi dere d as a si n gle lesi o n if t he y ca n be c o m pletel y 
treate d wit h 1 st u d y / c o ntr ol de vice . 
Pre dilati o n/ pretreat me nt of t he tar get lesi o n is re q uire d i n t his trial. If t he tar get lesi o n is n ot 
s uccessf ull y pre dilate d/ pretreate d, t he s u bject s h o ul d n ot be e nr olle d. If a n o n -tar get lesi o n is 
t o be treate d, it m ust  be treate d first a n d m ust be dee me d a n a n gi o gra p hic s uccess.  F oll o wi n g 
t he s uccessf ul treat me nt of t he n o n-tar get lesi o n, pre dilati o n of t he tar get lesi o n ma y t he n be 
perf or me d.   
N ote : S uccessf ul pre dilati o n/ pretreat me nt refers t o dilati o n wit h a ball o o n cat heter of 
a p pr o priate le n gt h a n d dia meter, or pretreat me nt wit h directi o nal or r otati o nal c or o nar y 
at herect o m y, laser or c utti n g/sc ori n g ball o o n wit h n o greater t ha n 5 0 % resi d ual ste n osis a n d 
n o dissecti o n greater t ha n Nati o nal Heart, L u n g, Bl o o d I nstit ute ( N H L BI) t y pe C . 
T hr o m b ol ysis i n M y ocar dial I nfarcti o n ( TI MI) gra de fl o w i n t he tar get lesi o n m ust be > 2  
 J ustific ati o n f or t he St u dy Desi g n  
T he A G E N T I D E  trial will e val uate t he safet y a n d effecti ve ness of t he A ge nt T M  Paclita xel 
C oate d P T C A Ball o o n Cat heter c o m pare d t o ball o o n a n gi o plast y ( P O B A) i n patie nts wit h i n -
ste nt reste n osis of a pre vi o usl y treate d lesi o n of u p t o 2 6  m m i n le n gt h ( b y vis ual esti mate) i n 
a nati ve c or o nar y arter y 2. 0 m m t o 4. 0 m m i n dia meter .    
 
P O B A is a wi del y use d treat me nt f or I S R, as t he 2 0 1 1 A C C F/ A H A/ S C AI G ui deli ne f or 
Perc uta ne o us C or o nar y I nter ve nti o n ( Le vi ne, et al), secti o n 6. 3. 4 rec o m me n ds use of P O B A 
t o treat f ocal reste n osis after D E S i m pla ntati o n, a n d t h us B S C feels t his is t he a p pr o priate 
c o ntr ol f or t his trial.  
 
T he A G E N T I D E  trial will i m ple me nt li mite d e xcl usi o n criteria s o t hat a br oa d ra n ge of 
s u bject a n d lesi o n c o m ple xities are st u die d i n t he trial. O n g oi n g d y na mic data safet y 
m o nit ori n g will be perf or me d t hr o u g h o ut t he trial t o mi ni mize s u bject  ris k. All e nr olle d 
s u bjects recei vi n g t he st u d y ball o o n will be f oll o we d f or 5  years p ost i n de x pr oce d ure.   

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 3 2  of 9 0  
  
8.  S u bject Selecti o n  
 St u dy  P o p ul ati o n a n d Eli gi bility  
Cli nical a n d a n gi o gra p hic i ncl usi o n a n d e xcl usi o n criteria f or t he A G E N T I D E trial are 
i ncl u de d i n Ta ble 8. 2 -1  a n d Ta ble 8. 3 -1  res pecti vel y. Pri or t o e nr oll me nt i n t he trial, a s u bject 
s h o ul d meet all of t he cli nical a n d a n gi o gra p hic i ncl usi o n criteria a n d n o ne of t he cli nical or 
a n gi o gra p hic e xcl usi o n criteria . 
 I ncl usi o n Criteri a 
S u bjects w h o meet all of t he f oll o wi n g criteria  (see Ta ble 8. 2 -1 ) ma y be gi ve n c o nsi derati o n 
f or i ncl usi o n i n t his cli nical i n vesti gati o n, pr o vi de d n o e xcl usi o n criteri o n (see Ta ble 8. 3 -1 ) is 
met.  

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 3 3  of 9 0  
  
 
 E xcl usi o n Criteri a  
T a ble 8. 2 -1 : I ncl usi o n Criteri a 
Cli nic al 
I ncl usi o n 
Criteri a  
CI 1.  
S u bject m ust be at least 1 8 years of a ge  
CI 2.  
S u bject ( or le gal g uar dia n) u n dersta n ds t he trial re q uire me nts a n d t he 
treat me nt pr oce d ures, a n d pr o vi des writte n i nf or me d c o nse nt bef ore 
a n y trial-s pecific tests or pr oce d ures are perf or me d 
CI 3.  
S u bject is eli gi ble f or perc uta ne o us c or o nar y i nter ve nti o n ( P CI)  
CI 4.  
S u bject is willi n g t o c o m pl y wit h all pr ot oc ol -re q uire d f oll o w-u p 
e val uati o n 
CI 5.  
W o me n of c hil d -beari n g p ote ntial m ust a gree t o use a relia ble  met h o d  
of c o ntrace pti o n fr o m t he ti me of scree ni n g t hr o u g h 1 2 m o nt hs after 
t he i n de x pr oce d ure  
A n gi o gr a p hic 
I ncl usi o n 
Criteri a 
( vis u al 
esti m ate)  
AI 1.  I n-ste nt reste n osis i n a lesi o n pre vi o usl y treate d wit h eit her a dr u g-
el uti n g ste nt or bare metal ste nt, l ocate d i n a nati ve c or o nar y arter y 
wit h a vis uall y esti mate d refere nce vessel dia meter ( R V D) > 2. 0 m m 
a n d ≤ 4. 0 m m.  
AI 2.  Tar get lesi o n le n gt h m ust be < 2 6  m m ( b y vis ual esti mate) a n d m ust be 
c o vere d b y o nl y o ne ball o o n.  
AI 3.  Tar get lesi o n m ust ha ve vis uall y esti mate d ste n osis > 5 0 % a n d < 1 0 0 % 
i n s y m pt o matic patie nts ( > 7 0 % a n d < 1 0 0 % i n as y m pt o matic patie nts) 
pri or t o lesi o n pre -dilati o n . 
AI 4 .  Tar get lesi o n m ust be s uccessf ull y pre -dilate d . 
N ote : S uccessf ul pre dilati o n/ pretreat me nt refers t o dilati o n wit h a ball o o n 
cat heter of a p pr o priate le n gt h a n d dia meter, or pretreat me nt wit h 
directi o nal or r otati o nal c or o nar y at herect o m y, laser or c utti n g/sc ori n g 
ball o o n wit h n o greater t ha n 5 0 % resi d ual ste n osis a n d n o dissecti o n 
greater t ha n Nati o nal Heart, L u n g, Bl o o d I nstit ute ( N H L BI) t y pe C.   
T hr o m b ol ysis i n M y ocar dial I nfarcti o n ( TI MI) gra de fl o w i n t he tar get 
lesi o n m ust be > 2  
 
AI 5 .  If a n o n-tar get lesi o n is treate d, it m ust be treate d first a n d m ust be 
dee me d a s uccess.  
N ote:  S uccessf ul treat me nt of a n o n -tar get lesi o n is defi ne d as a resi d ual 
ste n osis of ≤ 3 0 % i n 2 near -ort h o g o nal pr ojecti o ns wit h TI MI 3 fl o w, 
as vis uall y assesse d b y t he p h ysicia n, wit h o ut t he occ urre nce of 
pr ol o n ge d c hest pai n or E C G c ha n ges c o nsiste nt wit h MI . 
T a ble 8. 3 -1 : E xcl usi o n Criteri a 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 3 4  of 9 0  
  
Cli nic al 
E xcl usi o n 
Criteri a  
C E 1.  S u bject has ot her seri o us me dical ill ness (e. g. ca ncer, c o n gesti ve 
heart fail ure) t hat ma y re d uce life e x pecta nc y t o less t ha n 2 4 
m o nt hs.  
C E 2 .  S u bject has c urre nt pr o ble ms wit h s u bsta nce a b use (e. g. alc o h ol, 
c ocai ne, her oi n, etc.).  
C E 3 .  S u bject  has pla n ne d pr oce d ure t hat ma y ca use n o n -c o m plia nce 
wit h t he pr ot oc ol or c o nf o u n d data i nter pretati o n.  
C E 4 .  S u bject is partici pati n g i n a n ot her i n vesti gati o nal dr u g or de vice 
cli nical st u d y t hat has n ot reac he d its pri mar y e n d p oi nt.  
C E 5 . S u bject  i nte n ds t o partici pate i n a n ot her i n vesti gati o nal dr u g or 
de vice cli nical st u d y wit hi n 1 2 m o nt hs after t he i n de x pr oce d ure.  
C E 6 .  W o ma n w h o is pre g na nt or n ursi n g. ( A pre g na nc y test m ust be 
perf or me d wit hi n 7 da ys pri or t o t he i n de x pr oce d ure, e xce pt f or 
w o me n w h o defi nitel y d o n ot ha ve c hil d -beari n g p ote ntial.)  
C E 7 .  Left ve ntric ular ejecti o n fracti o n k n o w n t o be < 2 5 %.  
C E 8 .  Patie nt ha d P CI or  ot her c or o nar y i nter ve nti o ns wit hi n t he last 3 0 
da ys.  
C E 9 .  Pla n ne d P CI or C A B G after t he i n de x pr oce d ure.  
C E 1 0 .  S T E MI or Q W MI < 7 2 h  pri or t o t he i n de x pr oce d ure . 
C E 1 1 .  Car di o ge nic s h oc k ( S B P < 8 0 m m H g re q uiri n g i n otr o pes, I A B P or 
fl ui d s u p p ort). 
C E 1 2 . K n o w n aller gies a gai nst p aclita xel or ot her c o m p o ne nts of t he 
use d me dical de vices . 
C E 1 3 .  K n o w n h y perse nsiti vit y or c o ntrai n dicati o n f or c o ntrast d ye t hat i n 
t he o pi ni o n of t he i n vesti gat or ca n n ot be a de q uatel y pre-
me dicate d.  
C E 1 4 .  I nt olera nce t o a nti platelet dr u gs, a ntic oa g ula nts re q uire d f or 
pr oce d ure.  
C E 1 5 .  Platelet c o u nt < 1 0 0 k/ m m 3 (ris k of blee di n g) or > 7 0 0 k/ m m 3.  
C E 1 6.  S u bject  wit h re nal i ns ufficie nc y (creati ni ne ≥2. 0 m g/ dl) or fail ure 
( dial ysis de pe n de nt). 
C E 1 7.  S u bject has s us pecte d or pr o ve n C O VI D -1 9 at prese nt or wit hi n  
t he past 4  wee ks  wit h  res ol uti o n of s y m pt o ms. 
A n gi o gr a p hic 
E xcl usi o n 
Criteri a 
( vis u al 
esti m ate)  
A E 1. Tar get lesi o n is l ocate d wit hi n a bif urcati o n wit h pla n ne d treat me nt 
of si de bra nc h vessel.   
A E 2. Tar get lesi o n is l ocate d wit hi n a sa p he n o us vei n  or arterial  graft .  
A E 3 . T hr o m b us prese nt i n t he tar get vessel 
A E 4 . > 5 0 % ste n osis of a n a d diti o nal lesi o n pr o xi mal or cli nicall y 
si g nifica nt distal ( > 2. 0 m m R V D) t o t he tar get lesi o n. 
A E 5 .  S u bject  wit h u n pr otecte d left mai n c or o nar y arter y disease.  ( > 5 0 % 
dia meter ste n osis)  

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
 A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 3 5  of 9 0  
  
S u bjects w h o meet a n y o ne of t he a b o ve criteria (Ta ble 8. 3 -1 ) ca n n ot  be i ncl u de d i n t his 
st u d y a n d will be e xcl u de d fr o m t his cli nical st u d y. 
9.  S u bject Acc o u nt a bilit y  
 P oi nt of E nr oll me nt  
O nce t he s u bject has si g ne d t he I R B a p pr o ve d st u d y i nf or me d c o nse nt f or m (I C F) a n d has 
met all cli nical i ncl usi o n a n d n o cli nical e xcl usi o n criteria, t he s u bject s h o ul d be c o nsi dere d 
eli gi ble t o be e nr olle d i n t he trial. If t he s u bject is f o u n d t o meet e xcl usi o n criteria d uri n g t he 
a n gi o gra p hic eli gi bilit y assess me nt, t he s u bject will be c o nsi dere d a scree n fail ure a n d s h o ul d 
n ot be e nr olle d/ra n d o mize d or recei ve a n i n vesti gati o nal de vice, n or s h o ul d  t he s u bject be 
f oll o we d p ost pr oce d ure per pr ot oc ol.  If t he s u bject is f o u n d t o meet t he i ncl usi o n criteria 
d uri n g t he a n gi o gra p hic p hase of t he  pr oce d ure, t he s u bject will be c o nsi dere d eli gi ble t o be 
e nr olle d/ ra n d o mize d. T he Me di data Ra ve E D C s yste m will be use d t o assi g n s u bjects t o 
treat me nt gr o u p (st u d y/c o ntr ol) de vice . S u bjects will be c o nsi dere d e nr olle d after t he y ha ve 
bee n s uccessf ull y ra n d o mize d (i.e. w he n a treat me nt assi g n me nt is recei ve d b y t he 
i n vesti gati ve site). 
 Wit h dr a w al  
All s u bjects e nr olle d i n t he cli nical st u d y (i ncl u di n g t h ose wit h dra w n fr o m t he cli nical st u d y) 
s hall be acc o u nte d f or a n d d oc u me nte d. If a s u bject wit h dra ws fr o m t he cli nical 
i n vesti gati o n, t he reas o n(s) s hall be re p orte d. If s uc h wit h dra wal is d ue t o pr oble ms relate d t o 
i n vesti gati o nal de vice safet y or perf or ma nce, t he i n vesti gat or s hall as k f or t he s u bject’s 
per missi o n t o f oll o w his/ her stat us/c o n diti o n o utsi de of t he cli nical st u d y.    
 
W hile trial wit h dra wal is disc o ura ge d, s u bjects ma y c h o ose t o wit h dra w fr o m t he trial at a n y 
ti me, wit h or wit h o ut reas o n a n d wit h o ut prej u dice t o f urt her treat me nt. Wit h dra w n s u bjects 
will n ot u n der g o a n y a d diti o nal trial f oll o w -u p, n or will t he y be re pla ce d (t he j ustifie d sa m ple 
size c o nsi ders a n esti mate d all o wa nce f or attriti o n). T he reas o n f or wit h dra wal will be 
rec or de d (if gi ve n) i n all cases of wit h dra wal. If a s u bject  deci de s t o wit h dra w, he/s he  will be 
as ke d t o partici pate i n a li mite d ca pacit y al l o wi n g his/ her  me dical stat us t o be f oll o we d b y 
tele p h o ne c o ntact, me dical c hart re vie w, or b y ot her a gree d u p o n met h o d.  If t he s u bject 
deci de s n ot t o c o nti n ue partici pati o n i n a li mite d ca pacit y,  d ata t hat ha ve alrea d y bee n 
c ollecte d o n wit h dra w n s u bjects will be retai ne d a n d use d f or a nal ysis, b ut n o ne w data will 
be c ollecte d after wit h dra wal . T he I n vesti gat or ma y disc o nti n ue a s u bject fr o m partici pati o n 
i n t he trial if t he I n vesti gat or feels t hat t he s u bject ca n n o l o n ger f ull y c o m pl y wit h t he 
re q uire me nts of t he trial or if a n y of t he trial pr oce d ures are dee me d p ote ntiall y har mf ul t o 
t he s u bject.  
 
 

F or m/ Te m plate 9 0 7 0 2 6 3 7 Re v/ Ver A Q  
C o nfi de ntial    
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Pa ge 3 6  of 9 0  
  
 L ost t o F oll o w -U p  
A s u bject will be c o nsi dere d l ost t o f oll o w -u p after t he s u bject misses 2 c o nsec uti ve a n n ual 
f oll o w-u p visits. A mi ni m u m of 3 atte m pts (i.e. 2 p h o ne calls f oll o we d b y a certifie d letter, or 
ot her tracea ble letter, if necessar y) s h o ul d be ma de t o c o ntact t h e s u bject f or eac h misse d 
f oll o w-u p visit a n d t his i nf or mati o n d oc u me nte d i n t he s o urce.  
Misse d or late visits will be rec or de d as Pr ot oc ol De viati o ns . 
 E n d -of -St u dy Defi niti o n  
T he st u d y will be c o nsi dere d c o m plete wit h re gar d t o t he pri mar y e n d p oi nt after all patie nts 
ha ve c o m plete d t he 1 2 -m o nt h f oll o w -u p peri o d. A partici pa nt is c o nsi dere d t o ha ve 
c o m plete d t he st u d y if he or s he has c o m plete d  all p hases of t he st u d y i ncl u di n g t he last visit 
s h o w n i n t he Data C ollecti o n Sc he d ule (Ta ble 1 0. 1 -1 ). T he e n d of t he st u d y is defi ne d as 
c o m pleti o n of t he last patie nt last visit as s h o w n i n t he Data C ollecti o n Sc he d ule .  
 E nr oll me nt C o ntr ols  
T he A G E N T I D E  trial will i m ple me nt a f or mal E nr oll me nt C o m m u nicati o n Pla n. T he pla n 
will o utli ne t he s pecific acti vities a n d res p o nsi bilities of B S C e m pl o yees a n d re prese ntati ves, 
a n d nat ure a n d ti mi n g of c o m m u nicati o ns t o I n vesti gat ors as e nr oll me nt dra ws t o a cl ose. 
T he o bjecti ve of t he pla n is t o mi ni mize t he ris k of e nr oll me nt be y o n d t he pr ot oc ol -s pecifie d 
e nr oll me nt ca p of u p t o 6 0 0  s u bjects. 
1 0.  St u d y Met h o ds  
 D at a C ollecti o n  
T he data c olle cti o n sc he d ule is s h o w n i n  Ta ble 1 0. 1 -1 .  
 
 

  
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          C o nfi de ntial  
  
     
  
  
  
  
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Pa ge 3 7  of 9 0  
  
 
T a ble 1 0. 1 -1 : D at a C ollecti o n Sc he d ule  
  
 
 
Pr oce d ure/ Assess me nt  
B aseli ne/ 
Scree ni n g a 
P r oce d ure 
P ost pr oce d ure/ 
Disc h ar ge  
F oll o w -u p Visits  
3 0 D a ys  
( ± 7  D a ys) c 
Tele p h o ne 
I nter vie w or 
Office Visit  
6 M o nt hs  
( ± 3 0  D a ys) c 
Tele p h o ne 
I nter vie w 
or Office 
Visit  
1 2 M o nt hs   
( ± 3 0  D a ys) c 
Office Visit  
2 ye ar, 3 
ye ar  
( ± 3 0  D a ys) c 
Office Visit  
4 ye ar, 5 Ye ar  
( ± 3 0  D a ys) c 
Tele p h o ne 
I nter vie w or 
Office Visit  
I nf or me d c o nse nt pr ocess, i ncl u di n g 
i nf or me d c o nse nt si g nat ure dateb  
X  
 
 
 
 
 
 
 
E Q -5 D Q uesti o n naire  
X  
 
X  
 
 
X  
X  
 
De m o gra p hics, i ncl u di n g a ge, ge n der, a n d 
race a n d et h nicit y ( u nless restricte d b y l ocal 
la ws) 
X  
 
 
 
 
 
 
 
Me dical hist or y, i ncl u di n g dia betes mellit us 
stat usd  
X  
 
 
 
 
 
 
 
A n gi na assess me nt  
X  
 
X  
X  
X  
X  
X  
X  
Car diac e nz y mes e,f 
X  
 
X  
 
 
 
 
 
1 2 -lea d E C G 
X  
 
X  
 
 
X  
 
 
Ser u m creati ni ne / C B C a n d platelets   
X  
 
 
 
 
 
 
 
A ntit hr o m b otic me dicati o ns  
 
X  
 
 
 
 
 
 
A nti platelet me dicati o ns  
X   
X  
X  
X  
X  
X  
X  
X  
P CI pr oce d ure i nf or mati o n  f or tar get lesi o n   
X  
 
 
 
 
 
 
 
Pr oce d ural, tar get lesi o n, n o n -tar get lesi o n 
(if a p plica ble) pre dilati o n, p ost dilati o n (if 
a p plica ble), a n d st u d y de vice i nf or mati o n  
 
X  
 
 
 
 
 
 
A n gi o gra p h y  
 
X  
 
 
 
 
 
 
A E a n d A D E assess me nt  
 
X  
X  
X  
X  
X  
 
 
S A E, S A D E, U A D E, U S A D E, all C EC 
e ve nts a n d de vice deficie nc y assess me nt g  
 
X  
X  
X  
X  
X  
X  
X  
 
a: B aseli ne/ Scree ni n g assess me nts m ust t ake pl ace ≤ 1 4 D ays  bef ore pr oce d ure u nless ot her wise n ote d.  

  
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Pr oce d ure/ Assess me nt  
B aseli ne/ 
Scree ni n g a 
P r oce d ure 
P ost pr oce d ure/ 
Disc h ar ge  
F oll o w -u p Visits  
3 0 D a ys  
( ± 7  D a ys) c 
Tele p h o ne 
I nter vie w or 
Office Visit  
6 M o nt hs  
( ± 3 0  D a ys) c 
Tele p h o ne 
I nter vie w 
or Office 
Visit  
1 2 M o nt hs   
( ± 3 0  D a ys) c 
Office Visit  
2 ye ar, 3 
ye ar  
( ± 3 0  D a ys) c 
Office Visit  
4 ye ar, 5 Ye ar  
( ± 3 0  D a ys) c 
Tele p h o ne 
I nter vie w or 
Office Visit  
b : If t he st u dy I nf or me d C o nse nt F or m is m o difie d d uri n g t he c o urse of t he tri al, st u dy s u bjects will be re-c o nse nte d, if necess ary  
c: All f oll o w-u p d ates will be c alc ul ate d fr o m t he d ate of t he i n dex pr oce d ure. T he pr ot oc ol -re q uire d f oll o w-u ps m ay be perf or me d vi a tele p h o ne i ntervie w a n d/ or 
a n office visit wit hi n t he a p plic a ble f oll o w -u p wi n d o w  as n ote d i n t he pr ot oc ol . Bey o n d t he 1 2 -m o nt h f oll o w -u p, f oll o w -u p will be li mite d t o t he S afety P o p ul ati o n 
(e. g., t h ose st u dy s u bjects w h o receive d a st u dy/c o ntr ol device ). S u bjects w h o are e nr olle d b ut w h o d o n ot receive a st u dy / c o ntr ol device will be f oll o we d f or 1 2 
m o nt hs o nly.  
d :  Hei g ht a n d wei g ht s h o ul d be d oc u me nte d i n t he e C R F if av ail a ble i n t he s u bject me dic al rec or d   
e: Pre pr oce d ure c ar di ac e nzy mes c a n be dr a w n fr o m t he s he at h at t he ti me of s he at h i nserti o n.  If c ar di ac e nzy mes are dr a w n pre p r oce d ure, t he t w o res ults dr a w n 
cl osest t o t he pr oce d ure ti me s h o ul d be rec or de d i n t he e C R F.   
f: T w o c ar di ac e nzy me dr a ws m ust be o bt ai ne d at i nterv als per st a n d ar d of c are wit hi n 2 4 h o urs after t he i n dex pr oce d ure. T he first dr a w s h o ul d be perf or me d 6 -
1 2 h o urs p ost pr oce d ure a n d t he sec o n d dr a w s h o ul d be perf or me d 1 8 -2 4 h o urs p ost pr oce d ure .  If t he s u bject is disc h ar ge d pri or t o 1 8 h o urs p ost pr oce d ure, t he 
sec o n d dr a w s h o ul d be o bt ai ne d at t he ti me of disc h ar ge (it is rec o m me n de d t h at i n t hese c ases t he sec o n d dr a w occ ur n o e arli er t h a n 1 6 h o urs p ost pr oce d ure).  
g : S A Es, S A D Es, U A D Es, , C E C eve nts, a n d device deficie ncies will be m o nit ore d a n d re p orte d t o B S C fr o m t he ti me of e nr oll me nt t hr o u g h t he 1 2 -m o nt h f oll o w -
u p f or all s u bjects e nr olle d (re g ar dless of w het her a st u dy / c o ntr ol device  w as receive d) a n d bey o n d t he 1 2 -m o nt h f oll o w -u p t hr o u g h t he 5 -ye ar f oll o w -u p f or t he 
S afety P o p ul ati o n (e. g., t h ose st u dy s u bjects w h o receive d a st u dy / c o ntr ol device ). A Es a n d A D Es will o nly be c ollecte d t hr o u g h t he 1 2 -m o nt h f oll o w u p.   
 
A b bre viati o ns: A E = A d verse e ve nt, A D E =a d verse de vice effect; B S C = B ost o n Scie ntific C or p orati o n; P CI = perc uta ne o us c or o nar y i n ter ve nti o n; S A D E =seri o us 
a d verse de vice effect; S A E =seri o us a d verse e ve nts; U A D E = u na ntici pate d a d verse de vice effect  

F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A Q  
         C o nfi de ntial   
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Pa ge 3 9  of 9 0  
 
  
 St u dy C a n di d ate Scree ni n g  
St u d y pers o n nel  will  mai ntai n  d oc u me nt ati o n of s u bjects w h o fail t o meet t he A G E N T I D E 
trial eli gi bilit y criteria, i ncl u di n g t he reas o n f or scree n fail ure.   
 I nf or me d C o nse nt 
Bef ore a n y st u d y s pecific tests or pr oce d ures are perf or me d, s u bjects w h o meet eli gi bilit y 
criteria will be as ke d t o si g n t he I R B/I E C  a p pr o ve d st u d y I C F.  S u bjects m ust be gi ve n a m ple 
ti me t o re vie w t he I C F a n d ha ve q uesti o ns a ns were d bef ore si g ni n g. 
St u d y pers o n nel s h o ul d e x plai n t o t he s u bject t hat e ve n if t he s u bject a grees t o partici pate i n 
t he trial a n d si g ns t he I C F, car diac cat heterizati o n ma y de m o nstrate t hat t he s u bject is n ot a 
s uita ble ca n di date f or t he trial.  
Refer t o secti o n 9. 1 f or defi niti o n of p oi nt of e nr oll me nt. 
 B aseli ne  / Scree ni n g   
T he f oll o wi n g data m ust be c ollecte d  a n d m ust ta ke place ≤ 1 4 Da ys bef ore pr oce d ure u nless 
ot her wise n ote d :  
•  C o nfir mati o n of cli nical eli gi bilit y criteria  
•  De m o gra p hics i ncl u di n g a ge, ge n der, a n d race a n d et h nicit y ( u nless restricte d b y l ocal 
la ws) 
•  Me dical hist or y ( ge neral me dical, car diac, ne ur ol o gical, re nal a n d peri p heral hist or y), 
i ncl u di n g b ut n ot li mite d t o, t he f oll o wi n g: 
o  Dia betes mellit us stat us  
o  C urre nt a n gi na stat us  
o  Hei g ht a n d Wei g ht  (if a vaila ble) 
•  La b orat or y tests  
o  Ser u m creati ni ne 
o  C o m plete bl o o d c o u nt ( C B C) wit h platelets  
•  C urre nt a nti platelet me dicati o ns  
•  1 2 -lea d electr ocar di o gra m ( E C G) 
•  Tar get lesi o n: pre vi o us P CI pr oce d ure, v essel treate d, site treate d, a n d t y pe of pr oce d ure 
perf or me d  
•  Car diac E nz y mes  (see N ote 1, 2) 
•  E Q -5 D Q uesti o n naire  
 
N ote 1: Pre pr oce d ure car diac e nz y mes ca n be dra w n fr o m t he s heat h at t he ti me of s heat h 
i nserti o n. 
  
 

F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A Q  
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N ote 2: W hile C K -M B is t he preferre d car diac e nz y me, it is rec o m me n de d t hat t he sa me t y pe 
of car diac e nz y mes be a nal yze d pri or t o t he i n de x pr oce d ure a n d p ost pr oce d ure f or a gi ve n 
i n de x h os pitalizati o n (i.e., n ot s witc hi n g fr o m C K-M B t o tr o p o ni n or vice versa).  
   Re q uire d C o nc o mit a nt Me dic ati o ns  
Pr ot oc ol -re q uire d c o nc o mita nt me dicati o ns m ust be re p orte d i n t he electr o nic case re p ort 
f or m (e C R F) fr o m t he ti me of baseli ne t hr o u g h t he 5 -year f oll o w -u p . I nf or mati o n pertai ni n g 
t o t he use of a nti platelet me dicati o ns i ncl u di n g d ose c ha n ges, me dicati o n i nterr u pti o ns, a n d 
me dicati o n cessati o n, m ust be d oc u me nte d. A d diti o nal c o nc o mita nt me dicati o ns ma y be 
prescri be d at t he discreti o n of t he treati n g p h ysicia n acc or di n g t o sta n dar d of care.  
1 0. 5. 1.  L o a di n g D ose ( P 2 Y 1 2 i n hi bit or)  
•  F or s u bjects w h o ha ve bee n ta ki n g a P 2 Y 1 2 i n hi bit or f or  7 2  h o urs at t he ti me of t he 
i n de x pr oce d ure, a l oa di n g d ose is n ot re q uire d. 
•  F or s u bjects w h o ha ve n ot bee n ta ki n g a P 2 Y 1 2 i n hi bit or f or  7 2  h o urs at t he ti me of t he 
i n de x pr oce d ure, a l oa di n g d ose is rec o m me n de d. It is rec o m me n de d t hat t he l oa di n g 
d ose  be a d mi nistere d pri or t o t he i n de x pr oce d ure or n ot m ore t ha n  2  h o urs after t he i n de x 
pr oce d ure.  T he f oll o wi n g l oa di n g d oses are rec o m me n de d:  
o  Cl o pi d o grel: A peri -pr oce d ural l oa di n g d ose of ≥ 3 0 0 m g is rec o m me n de d.  
o  Pras u grel: A peri -pr oce d ural l oa di n g d ose of 6 0 m g is rec o m me n de d.  
o  Tica grel or: A peri -pr oce d ural l oa di n g d ose of 1 8 0 m g is rec o m me n de d.  
1 0. 5. 2.   L o a di n g D ose ( As piri n)  
•  F or s u bjects w h o ha ve bee n ta ki n g as piri n dail y f or ≥ 7 2  h o urs at t he ti me of t he i n de x 
pr oce d ure, a l oa di n g d ose is n ot re q uire d.  
•  F or s u bjects w h o ha ve n ot bee n ta ki n g as piri n dail y f or ≥ 7 2  h o urs at t he ti me of t he 
i n de x pr oce d ure, a l oa di n g d ose of as piri n is rec o m me n de d pri or t o t he i n de x pr oce d ure. 
T he d osa ge of t he l oa di n g d ose is at t he discreti o n of t he I n vesti gat or. It is rec o m me n de d 
t hat t he l oa di n g d ose be a d mi nistere d pri or t o t he i n de x pr oce d ure. 
1 0. 5. 3.   I n t he C ar di ac C at heteriz ati o n L a b or at or y 
T he s u bject m ust be treate d wit h he pari n or a n alter nati ve a ntit hr o m b otic (s uc h as bi valir u di n 
or e n o xa pari n) d uri n g t he i nter ve nti o nal p orti o n of t he pr oce d ure. If he pari n is use d, 
mai nte na nce of a n acti vate d cl otti n g ti me ( A C T) > 2 5 0 sec o n ds t hr o u g h o ut t h e i nter ve nti o nal 
p orti o n of t he pr oce d ure is rec o m me n de d. If e n o xa pari n or bi valir u di n is use d f or pr oce d ural 
a ntic oa g ulati o n, m o nit ori n g of t he a ntic oa g ulati o n le vel s h o ul d be perf or me d acc or di n g t o 
l ocal la b orat or y practice. 
N ote : Platelet gl yc o pr otei n II A/III B i n hi bit ors s uc h as A bci xi ma b, e ptifi bati de, a n d tir ofi ba n 
ma y be use d at t he discreti o n of t he I n vesti gat or.  
T o eli mi nate c or o nar y arter y s pas m t hat w o ul d i nterfere wit h acc urate meas ure me nt of l u me n 
o bstr ucti o n d ue t o pla q ue al o ne, i ntrac or o nar y nitr o gl yceri n ( N T G) or is os or bi de di nitrate 

F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A Q  
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(I S D N) s h o ul d be a d mi nistere d pri or t o t he baseli ne a n gi o gra m. A d ose of 1 0 0-2 0 0  g of 
i ntrac or o nar y N T G is preferre d; h o we ver, alter nati ve d oses of 5 0  g ma y be a d mi nistere d at 
t he I n vesti gat or’s discreti o n w he n dee me d cli nicall y necessar y. Alter nati vel y, if I S D N is 
a d mi nistere d, a n oral  d ose of 2 -3  m g is rec o m me n de d.  
1 0. 5. 4.   P ost pr oce d ure  
T he treat me nt descri be d i n t his secti o n is a p plica ble t o s u bjects w h o recei ve a st u d y/c o ntr ol 
de vice i n a tar get vessel. S u bjects w h o are e nr olle d b ut w h o d o n ot recei ve a st u d y/c o ntr ol 
de vice  s h o ul d be treate d per sta n dar d of care a n d f oll o we d per pr ot oc ol. 
It is req uire d t hat s u bjects recei ve a mi ni m u m of 1 -m o nt h d ual a nti-platelet t hera p y .  
A nti platelet  m o n ot hera p y s h o ul d be c o nti n ue d f or t he d urati o n of t he st u d y.      
1 0. 5. 4. 1.    O pti mal me dical t hera p y  
I n a d diti o n t o d ual a nti platelet t hera p y, it is rec o m me n de d t hat s u bjects be treate d wit h 
o pti mal me dical t hera p y (i ncl u di n g stati ns a n d beta bl oc kers) t o i m pr o ve o utc o mes. 
 C ar di ac C at heteriz ati o n  
1 0. 6. 1.   I n de x Pr oce d ure 
T he start of t he i n de x pr oce d ure is defi ne d as t he ti me of s heat h i nserti o n. If a pre vi o usl y 
place d s heat h is use d ( i.e., fr o m a se parate dia g n ostic pr oce d ure), i n de x pr oce d ure start ti me 
is defi ne d as t he ti me of g ui de cat heter i nserti o n i nt o s heat h f or t he i nter ve nti o nal pr oce d ure.  
D uri n g car diac cat heterizati o n, t he f oll o wi n g pr oce d ures a n d assess me nts m ust be c o m plete d.  
•  A n gi o gra p h y is t o be perf or me d acc or di n g t o t he A n gi o gra p hic C ore La b orat or y 
pr oce d ure g ui deli nes.  
•  C o nfir m a n gi o gra p hic eli gi bilit y criteria of lesi o n(s).  
•  Pre -dilate/ pretreat t he tar get lesi o n a n d n o n -tar get lesi o n (if a p plica ble). C o nfir mati o n of 
pre -dilati o n s uccess wit h I V U S is str o n gl y rec o m me n de d.    
•  If t he s u bject is ra n d o mize d t o recei ve st u d y treat me nt, t he n i nflate A ge nt D C B cat heter 
per I F U . 
•  If t he s u bject is ra n d o mize d t o t he c o ntr ol gr o u p a n a d diti o nal i nflati o n of at least 6 at m 
f or 3 0 sec s h o ul d f oll o w if o nl y a si n gle pre-dilati o n i nflati o n is necessar y.  
•  C o nfir mati o n of  all tar get lesi o n fi nal a n gi o gra p hic assess me nt b y I V U S is str o n gl y 
rec o m me n de d. 
N ote:  I V U S i m a gi n g perf or me d s h o ul d be se nt t o t he s p o ns or. 
 

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 E n d of t he I n de x Pr oce d ure  
T he e n d of t he i n de x pr oce d ure is defi ne d as t he ti me t he g ui di n g cat heter was re m o ve d ( p ost 
fi nal a n gi o gra p h y). T he i ntr o d ucer(s) s heat hs s h o ul d be re m o ve d as per sta n dar d l ocal 
practice. T he f oll o wi n g pr oce d ures m ust be c o m plete d:  
•  D oc u me nt pr oce d ural, tar get lesi o n, n o n -tar get lesi o n (if a p plica ble), pre-dilati o n, p ost -
dilati o n (if a p plica ble), a n d st u d y /c o ntr ol de vice  i nf or mati o n o n t he a p pr o priate e C R Fs. 
•  Rec or d a ntit hr o m b otic me dicati o ns  
•  C o m plete A E assess me nt a n d c ollect s o urce d oc u me nts as descri be d i n Secti o n 1 9  
•  Fi nalize a n gi o gra p hic pr oce d ure fil m a n d relate d re q uire d d oc u me ntati o n t o s u b mit t o t he 
C ore La b orat or y per i nstr ucti o ns set i n t he Ma n ual of O perati o ns . 
 P ost pr oce d ure/ Disc h ar ge  
T he s u bject ma y be disc har ge d fr o m t he h os pital w he n cli nicall y sta ble at t he I n vesti gat or’s 
discreti o n b ut prefera bl y n ot less t ha n 1 8  h o urs after t he i n de x pr oce d ure. T he f oll o wi n g 
assess me nts m ust be c o m plete d p ost i n de x pr oce d ure.  
•  A n gi na assess me nt  
•  Car diac e nz y mes  
T w o car diac e nz y me dra ws m ust be o btai ne d at i nter vals per sta n dar d of care wit hi n 
2 4  h o urs after t he i n de x pr oce d ure. T he first dra w s h o ul d be perf or me d 6 -1 2 h o urs 
p ost pr oce d ure a n d t he sec o n d dra w s h o ul d be perf or me d 1 8 -2 4 h o urs p ost pr oce d ure.  
N ote:  If t he s u bject is disc har ge d pri or t o 1 8 h o urs p ost pr oce d ure, t he sec o n d dra w 
s h o ul d be o btai ne d at t he ti me of disc har ge (it is rec o m me n de d t hat i n t hese cases t he 
sec o n d dra w occ ur n o earlier t ha n 1 6 h o urs p ost pr oce d ure). 
•  Rec or d a nti platelet me dicati o ns  
•  1 2 lea d E C G  
•  E Q -5 D  Q uesti o n naire  
•  C o m plete A E assess me nt a n d c ollect s o urce d oc u me nts as descri be d i n Secti o n 1 9   
It is i m p orta nt t hat trial site pers o n nel re vie w t he trial re q uire me nts wit h t he s u bject t o 
ma xi mize c o m plia nce wit h t he f oll o w-u p sc he d ule a n d re q uire d me dicati o n re gi me n. It is als o 
i m p orta nt t hat trial site pers o n nel i nstr uct s u bjects t o ret ur n f or f oll o w-u p assess me nts 
acc or di n g t o t he trial e ve nt sc he d ule i n  Secti o n 1 0 . St u d y staff s h o ul d esta blis h a date f or t he 
f oll o w-u p tele p h o ne call wit h t he s u bject a n d if p ossi ble, sc he d ule t he visit at t he ti me of 
h os pital disc har ge.  
 A n gi o gr a p hy  
All s u bjects will u n der g o a n gi o gra p hic assess me nt d uri n g t he i n de x pr oce d ure per sta n dar d 
of care. S u bjects re q uiri n g rei nter ve nti o n f o r t he tar get vessel d uri n g t he 5 -year f oll o w -u p 
peri o d will u n der g o a n gi o gra p hic assess me nt at t he ti me of rei nter ve nti o n as sta n dar d of care.  
A n gi o gra p hic data a n d i ma ges c ollecte d d uri n g t he i n de x pr oce d ure a n d d uri n g a n y 
rei nter ve nti o ns of a tar get vessel d uri n g t he 5 -year f oll o w -u p peri o d m ust be f or war de d t o t he 

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A n gi o gra p hic C ore La b orat or y f or a nal ysis. A n gi o gra ms perf or me d at a n o n-i n vesti gati o nal 
site s h o ul d als o be se nt t o t he C ore La b orat or y.  
A n gi o gra ms will be ce ntrall y assesse d f or q ualitati ve a n d q ua ntitati ve a nal ysis  b y t he 
A n gi o gra p hic C ore La b orat or y . I n a d diti o n, t he A n gi o gra p hic C ore La b orat or y will assess 
t he q ualit y of t he rec or di n gs a n d a d here nce t o t he ac q uisiti o n g ui deli nes pr o vi de selecte d 
q ualit y c o ntr ol fee d bac k if necessar y.  
 F oll o w -U p  
All e nr olle d s u bjects w h o recei ve a st u d y/c o ntr ol de vice, A G E N T T M  or P O B A , will be 
e val uate d t hr o u g h h os pital disc har ge a n d at 3 0 da ys, 6  m o nt hs, 1 2 m o nt hs , t he n a n n uall y 
t hr o u g h 5 years p ost i n de x pr oce d ure.  S u bjects w h o are e nr olle d b ut w h o d o n ot recei ve a 
st u d y/c o ntr ol de vice  will be f oll o we d f or 1 2  m o nt hs o nl y.  
All pr ot oc ol -re q uire d f oll o w-u p assess me nts m ust be c o n d ucte d wit h direct c o ntact wit h t he 
s u bjects eit her i n pers o n or b y tele p h o ne i nter vie w.  At t he ti me of eac h pr ot oc ol re q uire d 
f oll o w-u p, st u d y site pers o n nel s h o ul d a ns wer a n y st u d y relate d q uesti o ns  t he s u bject ma y 
ha ve i n a d diti o n t o c o m pleti n g t he re q uire d pr ot oc ol assess me nts. I n t he a bse nce of car diac 
s y m pt o ms, r o uti ne f oll o w-u p, car diac pr oce d ures, a n d tests are left t o t he discreti o n of t he 
I n vesti gat or.  
D uri n g t he 5 -year  f oll o w-u p peri o d, if t he s u bject e x perie nces a n e ve nt, it m ust be assesse d 
a n d d oc u me nte d as descri be d i n Secti o n 1 9.  If t he s u bject e x perie nces ne w or rec urre nt 
car diac s y m pt o ms d uri n g t he trial, a m ore detaile d e val uati o n (i ncl u di n g re peat a n gi o gra p h y) 
ma y be perf or me d at t he discreti o n of t he I n vesti gat or a n d treati n g p h ysicia ns.  
If t he s u bject u n der g oes re peat cat heterizati o n, t he circ u msta nces a n d o utc o me of t he e ve nt 
m ust be assesse d a n d d oc u me nte d as descri be d i n Secti o n 1 9 .  If t he re peat cat heterizati o n 
res ults i n rei nter ve nti o n of t he tar get vessel(s), a n gi o gra p hic data a n d i ma ges m ust be se nt t o 
t he A n gi o gra p hic C ore La b orat or y. 
S u bjects re q uiri n g rei nter ve nti o n s h o ul d be treate d acc or di n g t o t he I n vesti gat or’s discreti o n 
a n d sta n dar d of care. T hese s u bjects s h o ul d recei ve a n a p pr o ve d, c o m merciall y a vail a ble 
treat me nt (if a p pr o priate).  Pri or t o i nitiati n g a n a n gi o gra m, t he res ults of t he s u bjects’ 
cli nical stat us a n d f u ncti o nal testi n g s h o ul d be d oc u me nte d. Pri or t o c o n d ucti n g t he 
a n gi o gra m, i n dicati o n(s) f or t he a n gi o gra m m ust be d oc u me nte d.  
1 0. 1 0. 1.    
 3 0 -D a y F oll o w -u p ( 3 0 ± 7 D a ys)  
All e nr olle d s u bjects m ust be e val uate d 3 0 da ys after t he i n de x pr oce d ure. T he f oll o w -u p 
assess me nt ma y be perf or me d via tele p h o ne i nter vie w wit h t he s u bject or d uri n g a n office 
visit. D uri n g t he 3 0 -da y  f oll o w-u p, t he f oll o wi n g assess me nts m ust be c o m plete d.  
•  A n gi na assess me nt  
•  A E assess me nt a n d s o urce d oc u me nt c ollecti o n as descri be d i n Secti o n 1 9  
•  C urre nt a nti platelet me dicati o ns ( P 2 Y 1 2 i n hi bit or a n d as piri n). I nf or mati o n pertai ni n g t o 
d ose c ha n ges, me dicati o n i nterr u pti o ns, a n d me dicati o n cessati o n m ust be d oc u me nte d.  

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1 0. 1 0. 2.    
 6 -M o nt h F oll o w -u p ( 1 8 0 ± 3 0 D a ys)  
All e nr olle d s u bjects m ust be e val uate d 6 m o nt hs after t he i n de x pr oce d ure. T he f oll o w -u p 
assess me nt ma y be perf or me d via tele p h o ne i nter vie w wit h t he s u bject or d uri n g a n office 
visit. D uri n g t he 6 -m o nt h  f oll o w-u p, t he f oll o wi n g assess me nts m ust be c o m plete d.  
•  A n gi na assess me nt  
•  A E assess me nt a n d s o urce d oc u me nt c ollecti o n as descri be d i n Secti o n 1 9  
•  C urre nt a nti platelet me dicati o ns ( P 2 Y 1 2 i n hi bit or a n d as piri n). I nf or mati o n pertai ni n g t o 
d ose c ha n ges, me dicati o n i nterr u pti o ns, a n d me dicati o n cessati o n m ust be d oc u me nte d.  
1 0. 1 0. 3.    
 1 2 -M o nt h  F oll o w u p  ( ± 3 0 D a ys) 
All e nr olle d s u bjects m ust be e val uate d 1 2 m o nt hs  after t he i n de x pr oce d ure. T he f oll o w -u p 
assess me nt m ust be perf or me d wit h t he s u bject d uri n g a n office visit.  D uri n g t he 1 2 -m o nt h  
f oll o w-u p, t he f oll o wi n g assess me nts m ust be c o m plete d.  
•  A n gi na assess me nt  
•  1 2 -m o nt h  E C G  
•  E Q -5 D  Q uesti o n naire  
•  A E assess me nt a n d s o urce d oc u me nt c ollecti o n as descri be d i n Secti o n 1 9  
•  C urre nt a nti platelet me dicati o ns ( P 2 Y 1 2 i n hi bit or a n d as piri n). I nf or mati o n pertai ni n g t o 
d ose c ha n ges, me dicati o n i nterr u pti o ns, a n d me dicati o n cessati o n m ust be d oc u me nte d.  
1 0. 1 0. 4.  2 ye ar a n d 3 ye ar F oll o w u p  ( ± 3 0 D a ys) 
All e nr olle d s u bjects m ust be e val uate d at 2 years a n d 3 years  after t he i n de x pr oce d ure. T he 
f oll o w-u p assess me nt m ust be perf or me d wit h t he s u bject d uri n g a n office visit.  D uri n g t he 2 
year a n d 3 -year  f oll o w-u p, t he f oll o wi n g assess me nts m ust be c o m plete d.  
•  A n gi na assess me nt  
•  E Q -5 D Q uesti o n naire  
•  A E assess me nt a n d s o urce d oc u me nt c ollecti o n as descri be d i n Secti o n 1 9  
•  C urre nt a nti platelet me dicati o ns ( P 2 Y 1 2 i n hi bit or a n d as piri n). I nf or mati o n pertai ni n g t o 
d ose c ha n ges, me dicati o n i nterr u pti o ns, a n d me dicati o n cessati o n m ust be d oc u me nte d.  
1 0. 1 0. 5.  4 a n d 5 -Ye ar F oll o w -u p ( ± 3 0 D a ys)  
All e nr olle d s u bjects m ust be at e val uate d 4 a n d 5  years after t he i n de x pr oce d ure. T he 
f oll o w-u p assess me nt ma y be perf or me d via tele p h o ne i nter vie w wit h t he s u bject or d uri n g 
a n office visit. D uri n g t he a n n ual f oll o w-u p, t he f oll o wi n g assess me nts m ust be c o m plete d.  
•  A n gi na assess me nt  
•  A E assess me nt a n d s o urce d oc u me nt c ollecti o n as descri be d i n Secti o n 1 9  
•  C urre nt a nti platelet me dicati o ns ( P 2 Y 1 2 i n hi bit or a n d as piri n). I nf or mati o n pertai ni n g t o 
d ose c ha n ges, me dicati o n i nterr u pti o ns, a n d me dicati o n cessati o n m ust be d oc u me nte d.  

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 S o urce D oc u me nts  
It is prefera ble t hat ori gi nal s o urce d oc u me nts, w he n a vaila ble, are mai ntai ne d  at t he 
i n vesti gati ve ce nter. I n lie u of ori gi nal s o urce d oc u me nts, certifie d c o pies are re q uire d t o be 
mai ntai ne d.  A certifie d c o p y is a c o p y (irres pecti ve of t he t y pe of me dia use d) of t he ori gi nal 
rec or d t hat has bee n verifie d (i.e., b y a date d si g nat ure or b y ge nerati o n t hr o u g h a vali date d 
pr ocess) t o ha ve t he sa me i nf or mati o n, i ncl u di n g data t hat descri be t he c o nte xt, c o nte nt, a n d 
str uct ure, as t he ori gi nal. S o urce d oc u me ntati o n i ncl u des b ut is n ot li mite d t o t h ose ite ms 
n ote d i n  Ta ble 1 0. 1 1 -1 . 
T a ble 1 0. 1 1 -1 : S o urce D oc u me nt ati o n Re q uire me nts 
Re q uire me nt  
Dis p ositi o n  
 Pri nte d, o ptical, or electr o nic d oc u me nt c o ntai ni n g 
s o urce data. E xa m ples ma y i ncl u de b ut are n ot 
li mite d t o: h os pital rec or ds, la b orat or y n otes, de vice 
acc o u nta bilit y rec or ds, p h ot o gra p hic ne gati ves, 
ra di o gra p hs, rec or ds ke pt at t he i n vesti gati o n ce nter, 
at t he la b orat ories a n d at t he me dic o -tec h nical 
de part me nts i n v ol ve d i n t he cli nical i n vesti gati o n  
 
Retai n at ce nter.  
N ote:  Please see secti o n 2 5. 2 f or defi niti o ns of “s o urce data’ a n d “s o urce d oc u me nt” 
 A n gi o c ore l a b  d oc u me nt ati o n  
T his st u d y re q uires a n a n gi o gra p hic c ore la b orat or y.  A p pr o priate certificati o ns a n d 
d oc u me ntati o n rec or ds are re q uire d t o be mai ntai ne d at t he site f or la b orat or y a n d/ or ve n d ors.   
1 1.  St atistic al C o nsi der ati o ns  
 E n d p oi nts  
1 1. 1. 1.  Pri m ar y E n d p oi nt  
T he pri mar y e n d p oi nt of Tar get Lesi o n Fail ure at 1 2 m o nt hs f or t he A ge nt D C B ar m is 
s u peri or t o t hat f or t he P O B A ar m. 
1 1. 1. 1. 1.  H y p ot heses  
A z-test wit h u n p o ole d varia nce f or t he differe nce of t w o pr o p orti o ns will be use d t o test t he 
h y p ot hesis of s u peri orit y of D C B o ver P O B A i n t he 1 2 -m o nt h cli nical e n d p oi nt:  
H 0: T L FD C B  ≥ T L F P O B A   
H 1: T L FD C B  <  T L F P O B A   
w here T L F D C B  a n d T L F P O B A  are t he T L F t hr o u g h 1 2  m o nt hs  f or t he D C B a n d P O B A ar ms 
res pecti vel y. 
T he pri mar y a nal ysis set f or t he pri mar y e n d p oi nt is t he I nte nt t o treat a nal ysis set. T his 
e n d p oi nt will als o be a nal yze d f or t he per pr ot oc ol a nal ysis set . 

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A z-test wit h u n p o ole d varia nce f or t he differe nce of t w o pr o p orti o ns  will be use d t o test t he 
o ne -si de d h y p ot hesis of s u peri orit y bet wee n t he rates of t he t w o treat me nt gr o u ps. If t he P  
val ue fr o m t he z-test is < 0. 0 2 5 ( 1-si de d) a n d t he e ve nt rate of t he D C B gr o u p is less t ha n t he 
rate of t he P O B A  gr o u p , t he rate of T L F f or t he D C B gr o u p  will be c o ncl u de d t o be s u peri or 
t o t hat of t he P O B A . T his c orres p o n ds t o t he o ne -si de d 9 7. 5 %   u p per  c o nfi de nce b o u n d o n 
t he differe nce bet wee n treat me nt gr o u ps ( D C B  mi n us P O B A ) f or t he o bser ve d rate of t he 
pri mar y e n d p oi nt bei n g less t ha n zer o. 
1 1. 1. 1. 2.  Sa m ple Size  
T he sa m ple size calc ulati o n f or t he pri mar y e n d p oi nt is base d o n t he f oll o wi n g ass u m pti o ns:  
• 
E x pecte d mea n T L F D C B  = 1 0. 6 % ( base d o n meta -a nal ysis  of hist orical trials a n d 
i ncl u di n g a n a dj ust me nt t o acc o u nt f or t he oc ul o-ste n otic refle x)  
• 
E x pecte d mea n T L F P O B A  = 2 1. 2 % ( base d o n met a-a nal ysis of hist orical trials a n d 
i ncl u di n g a n a dj ust me nt t o acc o u nt f or t he o cul o -ste n otic refle x) 
• 
Test si g nifica nce le vel ( ) = 2. 5 % ( 1 -si de d) 
• 
P o wer =  8 5 %  
• 
Ra n d o mizati o n rati o = 2 D C B: 1 P O B A  
• 
N u m ber of e val ua ble s u bjects per ar m = 3 1 0 ( D C B) a n d 1 5 5 ( P O B A)  
• 
E x pecte d attriti o n rate = 3 %  
• 
T otal pla n ne d e nr oll me nt = 4 8 0 s u bjects, 32 0 i n D C B a n d 1 6 0  i n P O B A 
• 
A n  a da pti ve gr o u p se q ue ntial desi g n wit h o ne f or mal i nteri m a nal ysis f or t he pri mar y 
e n d p oi nt sa m ple size re-esti mati o n will be c o n d ucte d o n 1 -year data fr o m t he first 
4 0 % ( N = 1 9 2) ra n d o mize d  s u bjects of t he pla n ne d i nitial e nr oll me nt of 4 8 0 s u bjects.  
Details of t his a da pti ve a p pr oac h are pre -s pecifie d i n t he statistical a nal ysis pla n 
(S A P).  
A fi nal a nal ysis  f or t he P M A s u b missi o n will be c o n d ucte d o n t he n u m ber of ra n d o mize d 
s u bjects (at least 4 8 0 b ut u p t o 6 0 0 s u bjects) rec o m me n de d b y t he i n de pe n de nt D M C base d 
o n t he sa m ple size re -esti mati o n strate g y at t he i nteri m a nal ysis.  If t he pre-s pecifie d i nteri m 
a nal ysis i n dicates t hat t he st u d y s h o ul d be st o p pe d at 4 8 0 s u bjects, t he n o nl y t he first 4 8 0 
s u bjects will be c o nsi dere d f or t he pri mar y e n d p oi nt a nal ysis of t he st u d y i n t he P M A fili n g.   
If t he pre-s pecifie d i nteri m a nal ysis i n dicates t he st u d y e nr oll me nt will be less t ha n 6 0 0, t he 
pri mar y e n d p oi nt of all 6 0 0 e nr olle d s u bjects will als o be prese nte d.  
1 1. 1. 1. 3 A d diti o nal E n d p oi nts  
Cli nical e n d p oi nts meas ure d i n h os pital a n d at 3 0 da ys, 6  m o nt hs, 1 2 m o nt hs,  t he n a n n uall y 
t hr o u g h 5 years. A d diti o nal cli nical e n d p oi nts i ncl u de:  
• 
Tar get lesi o n re vasc ularizati o n ( T L R) rate, Tar get lesi o n fail ure ( T L F) rate 
( pri mar y e n d p oi nt at 1 2  m o nt hs), Tar get vessel re vasc ularizati o n ( T V R) rate  
• 
Tar get vessel fail ure ( T V F) rate  
• 
MI ( Q -wa ve a n d n o n – Q -wa ve) rate  (P P MI per t he S C AI defi niti o n  a n d 
s p o nta ne o us MI per t he 4 t h U ni versal defi niti o n ) 
• 
Car diac deat h rate  

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• 
N o n -car diac deat h rate  
• 
All -ca use deat h rate  
• 
Ste nt t hr o m b osis rates ( per Aca de mic Researc h C o ns orti u m [ A R C] defi niti o ns)  
Peri pr oce d ural e n d p oi nt:  
• 
Tec h nical s uccess rate  
• 
Cli nical pr oce d ural s uccess rate  
C ha n ge i n Q ualit y of Life:  
• 
F u ncti o nal stat us of ge neral healt h -relate d q ualit y of life meas ure d b y c ha n ges i n 
E Q -5 D sc ores at h os pital disc har ge, 1 2 m o nt hs, 2 4  m o nt hs a n d 3 6  m o nt hs  
 Ge ner al St atistic al Met h o ds  
1 1. 2. 1.  A n al ysis Sets  
All pri mar y a n d a d diti o nal e n d p oi nts will be a nal yze d b ot h o n a n i nte nt -t o-treat basis a n d o n 
a per -pr ot oc ol basis . F or i nte nt -t o-treat a nal yses, all s u bjects w h o si g n t he I R B/I E C -a p pr o ve d 
st u d y I C F a n d are e nr olle d i n t he st u d y will be i ncl u de d i n t he a nal ysis acc or di n g t o t heir 
ra n d o mize d treat me nt, re gar dless of w het her or n ot a st u d y A ge ntT M  Paclita xel C oate d P T C A 
Ball o o n Cat heter or a c o ntr ol ball o o n a n gi o plast y ( P O B A) was use d.  
F or per -pr ot oc ol a nal yses, o nl y s u bjects w h o ha d t he assi g ne d st u d y /c o ntr ol de vice 
( A G E N TT M  D C B or P O B A) recei ve d i n t he tar get c or o nar y arter y at t he i n de x pr oce d ure will 
be i ncl u de d i n t he a nal ysis. F or s u bjects i n t he R C T wit h a tar get lesi o n, a st u d y/c o ntr ol 
de vice m ust be use d t o treat t he tar get lesi o n f or t he patie nt t o be i ncl u de d i n t he per -pr ot oc ol 
a nal ysis set.  
F or eli gi ble patie nts w h o cr oss o ver fr o m P O B A t o A G E N T D C B, t he y are c o nsi dere d t o 
ha ve e x perie nce d  a st u d y e n d p oi nt e ve nt of T L R a n d are ce ns ore d at t he ti me of cr oss o ver f or 
t he a nal ysis of ot her cli nical e n d p oi nts i n t he per-pr ot oc ol a nal yses . I n a d diti o n, e ve nts wit h 
o nset dates o n or after t he ti me of cr oss o ver treat me nt will be s u m marize d se paratel y.   T hese 
e ve nts will be i ncl u de d i n t he I T T a nal yses.  
1 1. 2. 2.  C o ntr ol of S yste m atic Err or/ Bi as  
S u bjects i n t he R C T will be ra n d o ml y assi g ne d t o treat me nt gr o u ps a n d patie nts will re mai n 
bli n de d t o treat me nt t hr o u g h o ut t he c o urse of t he st u d y.  Selecti o n of s u bjects will be ma de 
fr o m t he I n vesti gat or’s us ual patie nt l oa d.  All s u bjects meeti n g t he eli gi bilit y criteria a n d 
ha vi n g si g ne d t he I C F will be eli gi ble f or e nr oll me nt i n t he st u d y.  I n deter mi ni n g s u bject 
eli gi bilit y f or t he st u d y, t he I n vesti gat or’s assess me nt of a n gi o gra p hic para meters bef ore 
de vice place me nt will be use d.  H o we ver, t o c o ntr ol f or i nte r o bser ver varia bilit y a m o n g sites, 
a n A n gi o gra p hic C ore La b orat or y will deter mi ne t he a n gi o gra p hic res ults t o be use d i n t he 
data a nal yses.  A n i n de pe n de nt C E C c o m p ose d of e x pert car di ol o gists will a dj u dicate all 
re p orte d e ve nts of deat h, MI, T V R  a n d Ste nt T hr o m b osis .   

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1 1. 2. 3.  N u m ber of S u bjects per I n vesti g ati ve Site  
A c o m p uter -ge nerate d list of ra n d o m treat me nt all ocati o ns (i.e., a ra n d o mizati o n sc he d ule) 
will be use d t o assi g n s u bjects t o treat me nt i n a 2 : 1 rati o of D C B t o P O B A . Ra n d o mizati o n 
will be stratifie d b y ce nter a n d si n gle vs. m ulti ple ste nt la yer  reste n osis.  Eac h site will e nr oll 
n o m ore t ha n 2 0 % of s u bjects  of t he t otal sa m ple size. 
 D at a A n alyses  
Baseli ne a n d  o utc o me varia bles will be s u m marize d usi n g descri pti ve statistics f or 
c o nti n u o us varia bles ( mea n, sta n dar d de viati o n, n u m ber of o bser vati o ns, mi ni m u m a n d 
ma xi m u m) a n d discrete varia bles  ( perce nta ge a n d c o u nt/sa m ple). See Secti o n 1 1. 1 f or a 
disc ussi o n o n a nal ysis of t he pri mar y e n d p oi nt a n d a d diti o nal meas ure me nts . 
1 1. 3. 1.  A n al ysis of MI E ve nts  
T he c o m p osite e n d p oi nt of T L F  is c o m prise d of car diac deat h, MI relate d t o t he tar get vessel, 
a n d tar get lesi o n re vasc ularizati o n.  T he MI e ve nts i ncl u de t he P P MI acc or di n g t o t he S C AI 
MI defi niti o n wit hi n 4 8 h o urs of t he i n de x pr oce d ure a n d t he s p o nta ne o us MI acc or di n g t o 
t he 4t h U ni versal MI defi niti o n after 4 8 h o urs of t he i n de x pr oce d ure.  
F or t he P P MI acc or di n g t o t he S C AI MI defi niti o n, t he u nifie d U p per Li mit of N or mal 
( U L N) of 0. 0 4 5 n g/ m L f or Tr o p o ni n I a n d t he u nifie d U L N of 0. 0 2 2 n g/ m L f or Tr o p o ni n T 
will be a p plie d t o deter mi ne t he car diac e nz y me ele vati o n (i n ter ms of m ulti ple ti mes relati ve 
t o t he U L N).  T his is a n a gree d a p pr oac h wit h t he F D A t o a d dress t he heter o ge neit y of t he 
vari o us U L Ns fr o m all l ocal la b orat ories i n t he A G E N T I D E st u d y.  
All C E C re p orta ble P P MI e ve nts usi n g t he u nifie d U L Ns of Tr o p o ni n I a n d T t o deter mi ne 
t he car diac e nz y me ele vati o n acc or di n g t o t he S C AI MI defi niti o n will be a dj u dicate d b y 
C E C . 
1 1. 3. 2.  Ot her E n d p oi nts/ Me as ure me nts  
Ot her meas ure me nts n ot dri ve n b y statistical h y p ot heses are liste d i n Secti o n  1 1. 1. 1. 3 . 
1 1. 3. 3.  I nteri m A n al yses  
O ne  pla n ne d f or mal i nteri m a nal ys is as descri be d i n t he Statistical A nal ysis Pla n  f or sa m ple 
size re-esti mati o n will be c o n d ucte d o n t he first 4 0 % ( N = 1 9 2) ra n d o mize d s u bjects wit h 1 -
year f oll o w u p . T he p ur p ose of t he i nteri m a nal ysis is t o deter mi ne t he sa m ple size f or t he 
pri mar y a nal ysis f or t he P M A  s u b missi o n.   
1 1. 3. 4.  S u b gr o u p A n al yses  
Pri mar y a n d pre -s pecifie d a d diti o nal e n d p oi nts will be s u m marize d a n d treat me nt gr o u ps will 
be c o m pare d f or t he f oll o wi n g s u b gr o u ps of ra n d o mize d s u bjects. 
•  Ge n der ( male a n d fe male)  

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•  A ge ( < 7 5 a n d ≥ 7 5 years)  
•  Dia betic Stat us  
•  S mall Vessel vs Lar ger Vessel ( R V D < 2. 7 5 a n d ≥ 2. 7 5 m m)  
•  O ne ste nt la yer reste n osis a n d M ulti ple ste nt la yer reste n osis (rec urre nt reste n osis) 
•  Tar get lesi o n o nl y a n d Tar get lesi o n pl us 1 n o n -tar get lesi o n treate d 
•  B M S a n d D E S  Reste n osis.  
•  C T O a n d n o n -C T O  
N o a dj ust me nts f or m ulti ple c o m paris o ns will be ma de.    
1 1. 3. 5.  J ustific ati o n of P o oli n g  
A nal yses f or the pri mar y e n d p oi nt will be prese nte d usi n g data p o ole d acr oss i nstit uti o ns . A n 
assess me nt of t he p o ola bilit y of s u bjects acr oss ce nter s will be ma de usi n g l o gistic re gressi o n 
wit h cli nical ce nter as a fi xe d effect a n d a ge neralize d li near mi xe d m o del wit h a cli nical 
ce nter as a  ra n d o m effect. T he de pe n de nt varia ble is t he pri mar y e n d p oi nt of 1 2 -m o nt h T L F, 
t he i n de pe n de nt varia bles are treat me nt, cli nical ce nter , a n d t he c orres p o n di n g treat me nt b y 
cli nical ce nter  i nteracti o n w hic h are t he fi xe d effects i n t he l o gistic re gressi o n m o del. A 
sec o n d mi xe d li near re gressi o n m o del usi n g t he cli nical ce nter as a ra n d o m effect i n t he 
ra n d o m effect l o gistic re gressi o n m o del will als o be perf or me d b y usi n g pr oc gli m mix  i n 
S A S.  If t he P val ue s f or cli nical ce nter b y treat me nt i nteracti o n i n t he t w o m o dels are ≥0. 1 5, 
it ca n be c o ncl u de d t hat t he treat me nt effect is n ot differe nt acr oss t he ce nters a n d t he data 
ca n be p o ole d.  I n t he a nal ysis t o j ustif y p o oli n g acr oss ce nters, t he ce nters wit h fe wer t ha n 
6  s u bjects e nr olle d i n t he st u d y will be re m o ve d fr o m t he a nal ysis. 
1 1. 3. 6.  M ulti v ari a ble A n al yses  
U ni variate a n d m ulti variate a nal yses will be perf or me d t o assess t he effect of p ote ntial 
pre dict ors o n t he pri mar y e n d p oi nt as descri be d  i n t he S tatistical A nal ysis P la n. 
1 1. 3. 7.  C h a n ges t o Pl a n ne d A n al yses  
A n y c ha n ges t o t he pla n ne d statistical a nal yses ma de pri or t o  perf or mi n g t he a nal yses  will be 
d oc u me nte d i n a n a me n de d Statistical A nal ysis Pla n a p pr o ve d pri or t o  perf or mi n g t he 
a nal yses.  C ha n ges fr o m t he pla n ne d statistical met h o ds after  perf or mi n g t he a nal yses w ill be 
d oc u me nte d i n t he cli nical st u d y re p ort al o n g wit h a reas o n f or t he de viati o n.  
1 2.  Q u alit y of Life  
T he Q O L i nstr u me nts use d f or t he trial will be t he E Q -5 D f or ge neral healt h.  
T he E Q -5 D is a descri pti ve s yste m of healt h -relate d q ualit y of life states c o nsisti n g of fi ve 
di me nsi o ns ( m o bilit y, self -care, us ual acti vities, pai n/ disc o mf ort, a n xiet y/ de pressi o n) eac h of 
w hic h ca n ta ke o ne of fi ve res p o nses. T he res p o nses rec or d fi ve le vels of se verit y ( n o 

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pr o ble ms/sli g ht pr o ble ms/ m o derate pr o ble ms/se vere pr o ble ms/e xtre me pr o ble ms) wit hi n a 
partic ular E Q -5 D di me nsi o n .  
1 3.  D at a M a n a ge me nt  
 D at a C ollecti o n, Pr ocessi n g, a n d Revie w  
S u bject data will be rec or de d i n a li mite d access sec ure electr o nic data ca pt ure ( E D C) 
s yste m.  
T he cli nical data base will resi de o n a pr o d ucti o n ser ver h oste d b y Me di data E D C S yste m . All 
c ha n ges ma de t o t he cli nical data will be ca pt ure d i n a n electr o nic a u dit trail a n d a vaila ble f or 
re vie w b y t he s p o ns or or its re prese ntati ve. T he ass ociate d R a ve s oft ware a n d data base ha ve 
bee n desi g ne d t o meet re g ulat or y c o m plia nce f or de pl o y me nt as part of a vali date d s yste m 
c o m plia nt wit h la ws a n d re g ulati o ns a p plica ble t o t he c o n d uct of cli nical st u dies pertai ni n g t o 
t he use of electr o nic rec or ds a n d si g nat ures. Data base bac k u ps are perf or me d re g ularl y.  
T he I n vesti gat or pr o vi des his/ her electr o nic si g nat ure o n t he a p pr o priate electr o nic case 
re p ort f or ms (e C R Fs) i n c o m plia nce wit h l ocal re g ulati o ns. A writte n si g nat ure o n pri nt o uts 
of t he e C R Fs m ust als o be pr o vi de d if re q uire d b y l ocal re g ulati o n. C ha n ge s t o data 
pre vi o usl y s u b mitte d t o t he s p o ns or re q uire a ne w electr o nic si g nat ure b y t he I n vesti gat or 
ac k n o wle d gi n g a n d a p pr o vi n g t he c ha n ges.  
Vis ual a n d/ or electr o nic data re vie w will be perf or me d t o i de ntif y p ossi ble data 
discre pa ncies. Ma n ual a n d/ or a ut o matic q ueries will be create d i n t he Me di data E D C s yste m 
a n d will be iss ue d t o t he site f or a p pr o priate res p o nse. Site staff will be res p o nsi ble f or 
res ol vi n g all q ueries i n t he data base. 
All access t o t he cli nical data base will be c ha n ge d t o “ Rea d o nl y” after all data is eit her 
“ Har d L oc ke d” or “ E ntr y L oc ke d”. O nce acce pta nce of t he fi nal re p ort or fi nalizati o n of 
p u blicati o ns (as a p plica ble) is recei ve d, fi nal data base st ora ge a n d arc hi vi n g acti vities ca n 
be gi n. O nce all of t he cl ose o ut acti vities are c o m plete d a re q uest t o I T is s u b mitte d t o ha ve 
t he “ Data base L oc ke d” or Dec o m missi o ne d a n d all data base access re v o ke d. 
 D at a Rete nti o n  
T he Pri nci pal I n vesti gat or or his/ her desi g nee or I n vesti gati o nal site will mai ntai n  all 
esse ntial st u d y d oc u me nts a n d s o urce d oc u me ntati o n t hat s u p p ort t he data c ollecte d o n t he 
st u d y s u bjects i n c o m plia nce wit h a p plica ble re g ulat or y re q uire me nts .   
T he Pri nci pal I n vesti gat or or his/ her desi g nee will ta ke meas ures t o pre ve nt acci de ntal or 
pre mat ure destr ucti o n of t hese d oc u me nts . If f or a n y reas o n t he Pri nci pal I n vesti gat or or 
his/ her desi g nee wit h dra ws res p o nsi bilit y f or mai ntai ni n g t hese esse ntial d oc u me nts, c ust o d y 
m ust be tra nsferre d t o a n i n di vi d ual w h o will ass u me res p o nsi bilit y a n d B S C m ust recei ve 
writte n n otificati o n of t his c ust o dial c ha n ge. Sites are re q uire d t o i nf or m B ost o n Scie ntific i n 
writi n g w here pa per or electr o nic files are mai ntai n e d i n case files are st ore d off site a n d are 
n ot rea dil y a vaila ble.  

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 C ore L a b or at ories  
T he A G E N T I D E  trial will use a n A n gi o gra p hic C ore La b orat or y f or a nal ysis of a n gi o gra p h y 
data.  Res ults fr o m t he a n gi o gra p hic C ore La b orat or y will be e ntere d or u pl oa de d i nt o t he 
E D C s yste m a n d will o nl y be a vaila ble t o B S C.  
All s u bjects will u n der g o a n gi o gra p hic assess me nt d uri n g t he i n de x pr oce d ure. A n gi o gra p hic 
f oll o w-u p is n ot re q uire d; h o we ver, s u bjects re q uiri n g rei nter ve nti o n f or t he tar get vessel 
d uri n g t he 5 -year f oll o w -u p peri o d will u n der g o a n gi o gra p hic assess me nt at t he ti me of 
rei nter ve nti o n as sta n dar d of care. 
A n gi o gra p hic data, i ma ges  (i ncl u di n g I V U S a n d O C T), a n d tec h nicia n’s w or ks heets 
c ollecte d d uri n g t he i n de x pr oce d ure a n d d uri n g rei nter ve nti o ns f or t he tar get vessel(s) d uri n g 
t he 5 -year f oll o w -u p peri o d (if a p plica ble) m ust be f or war de d t o t he A n gi o gra p hic C ore 
La b orat or y f or a nal ysis. A n gi o gra p hic data a n d i ma ges f or rei nter ve nti o n f or vessels n ot 
treate d d uri n g t he st u d y i n de x pr oce d ure s h o ul d n ot be se nt t o t he A n gi o gra p hic C ore 
La b orat or y.  
1 4.  Pr ot oc ol De vi ati o ns  
A n I n vesti gat or m ust n ot ma ke a n y c ha n ges or de viate fr o m t his pr ot oc ol , e xce pt t o pr otect 
t he life a n d p h ysical well-bei n g of a s u bject i n a n e mer ge nc y. A n i n vesti gat or s hall n otif y t he 
s p o ns or a n d t he re vie wi n g I R B/ EC / R E B, a n d t he re g ulat or y a ut h orit y if a p plica ble of a n y 
de viati o n fr o m t he i n vesti gati o nal pla n t o pr otect t he life or p h ysical well -bei n g of a s u bject 
i n a n e mer ge nc y, a n d t h ose de viati o ns w hic h affect t he scie ntific i nte grit y of t he cli nical 
i n vesti gati o n. S uc h n otice s hall be gi ve n as s o o n as p ossi ble, b ut n o later t ha n 5  w or ki n g da ys 
after t he e mer ge nc y occ urre d, or per pre vaili n g l ocal re q uire me nts, if s o o ner t ha n 5  w or ki n g 
da ys.  
All de viati o ns fr o m t he i n vesti gati o nal pla n, wit h t he reas o n f or t he de viati o n a n d t he date of 
occ urre nce, m ust be d oc u me nte d a n d re p orte d t o t he s p o ns or  usi n g  E D C.  Sites ma y als o be 
re q uire d t o re p ort de viati o ns t o t he I R B/ E C/ R E B, per l ocal g ui deli nes a n d g o ver n me nt 
re g ulati o ns.  
De viati o ns will be re vie we d a n d e val uate d o n a n o n g oi n g basis a n d, as necessar y, a p pr o priate 
c orrecti ve a n d pre ve nti ve acti o ns (i ncl u di n g b ut n ot li mite d t o, I R B/ F D A n otificati o n, site re-
trai ni n g, or site disc o nti n uati o n /ter mi nati o n) will be p ut i nt o place b y t he s p o ns or. 
T he s p o ns or will n ot a p pr o ve pr ot oc ol wai vers.  
1 5.  De vice  Acc o u nt a bilit y  f or Pr o d ucts L a belle d I n vesti g ati o n al 
T he i n vesti gati o nal de vices  s hall be sec urel y mai ntai ne d, c o ntr olle d, a n d use d o nl y i n t his 
cli nical st u d y. A d diti o nall y, st u d y pers o n nel m ust f oll o w t he i nstr ucti o ns relate d t o t he 
st ora ge of t he test de vice as n ote d i n t he c orres p o n di n g cli nical D F U. A n electr o nic 
i nteracti ve res p o nse tec h n ol o g y (I R T) will be use d f or i n vesti gati o nal de vice ma na ge me nt  
a n d acc o u nta bilit y d uri n g t he st u d y . 

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F or i n vesti gati o nal -la belle d ite ms, t he P ri nci pal In vesti gat or or a n a ut h orize d desi g nee s hall 
d o t he f oll o wi n g:  
•  Sec urel y mai ntai n a n d c o ntr ol access t o t hese ite ms t o e ns ure t he y are use d o nl y 
i n t his cli nical st u d y a n d o nl y per t he pr ot oc ol.  
•  E ns ure t he st ora ge e n vir o n me nt f or t hese ite ms is a p pr o priate f or mai ntai ni n g 
c o n diti o ns per t he ite ms’ la beli n g (e. g. te m perat ure, h u mi dit y, etc., as a p plica ble)  
•  Ret ur n re mai ni n g ite ms u p o n S p o ns or re q uest a n d i n t he c o n diti o n i n w hic h t he y 
were pr o vi de d, reas o na ble wear a n d tear e xce pte d  
 
T he s p o ns or or desi g nee s hall kee p rec or ds t o d oc u me nt t he p h ysical l ocati o n of all 
i n vesti gati o nal de vices fr o m s hi p me nt of i n vesti gati o nal de vices fr o m B S C or desi g nate d 
facilit y t o t he i n vesti gati o n sites u ntil ret ur n or dis p osal. T he I R T will be use d t o d oc u me nt 
rece pti o n of t he i n vesti gati o nal de vice at a ce nter. 
Rec or ds s hall be ke pt b y a ut h orize d site st u d y pers o n nel  t o d oc u me nt t he p h ysical l ocati o n 
a n d c o n diti o ns of st ora ge of all i n vesti gati o nal de vices. Sites  m ust n ot dis p ose of a n y 
i n vesti gati o nal de vices f or a n y reas o n at t he site u nless i nstr ucte d t o d o s o b y B S C. A n y 
i n vesti gati o nal de vice t hat is dis p ose d of at t he site m ust be d oc u me nte d a p pr o priatel y . Sites 
m ust d oc u me nt t he reas o ns f or a n y discre pa nc y n ote d i n de vice acc o u nta bilit y . 
T he pri nci pal i n vesti gat or or a n a ut h orize d desi g nee s hall kee p rec or ds d oc u me nti n g t he 
recei pt, use, ret ur n a n d dis p osal of t he i n vesti gati o nal de vices, w hic h s hall i ncl u de t he 
f oll o wi n g: 
•  Na me(s) of pers o n(s) w h o recei ve d, use d, ret ur ne d, or dis p ose d of eac h ite m  
•  Date of recei pt  at t he site  
•  I de ntificati o n of eac h i n vesti gati o nal de vice ( u ni q ue i de ntifier or l ot n u m ber/ batc h 
n u m ber/serial n u m ber ) 
•  E x pir y date, as a p plica ble  
•  Date of use  
•  S u bject i de ntificati o n  
•  Date of ret ur n a n d q ua ntit y of all i n vesti gati o nal de vices  of u n use d, e x pire d, or 
malf u ncti o ni n g i n vesti gati o nal de vices, if a p plica ble.  
O nce t he I n vesti gat or a n d site are n otifie d i n writi n g b y B S C t hat s u bject e nr oll me nt is 
c o m plete, all u n use d i n vesti gati o nal de vices m ust be ret ur ne d t o B S C  or its desi g nee . 
  Device Acc o u nt a bility f or t he C o ntr ol Device  
A p pr o priate i nf or mati o n o n t he c o ntr ol de vice size will be c ollecte d.  

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1 6.  C o m pli a nce  
 St ate me nt of C o m pli a nce  
T his cli nical i n vesti gati o n is fi na nce d b y t he st u d y s p o ns or. Bef ore t he i n vesti gati o nal site 
ca n be “ A ut h orize d t o E nr oll,” t he i n vesti gati o nal site m ust e nter i nt o a Cli nical St u d y 
A gree me nt wit h t he s p o ns or t hat details t he fi na nci n g of t he st u d y as wel l as t he ri g hts a n d 
o bli gati o ns of t he i n vesti gati o nal site a n d t he i n vesti gat or.  
 
T his st u d y will be c o n d ucte d i n acc or da nce wit h  I S O 1 4 1 5 5 Cli nical I n vesti gati o n of Me dical 
De vices f or H u ma n S u bjects - G C P, or t he rele va nt parts of t he I C H G ui deli nes f or G C P , 
et hical pri nci ples t hat ha ve t heir ori gi ns i n t he Declarati o n of Helsi n ki, a n d a p plica ble 
i n di vi d ual c o u ntr y la ws a n d re g ulati o ns. T he st u d y s hall n ot be gi n u ntil t he re q uire d 
a p pr o val/fa v ora ble o pi ni o n fr o m t he I R B  a n d/ or re g ulat or y a ut h orit y has bee n o btai ne d, if 
a p pr o priate. Als o, t he st u d y s hall n ot be gi n pri or t o iss ua nce of t he site A ut h orizati o n t o 
E nr oll, as pr o vi de d b y t he s p o ns or. A n y a d diti o nal re q uire me nts i m p ose d b y t he 
I R B/ E C/ R E B or re g ulat or y a ut h orit y s hall be f oll o we d, if a p pr o priate.   
 I nvesti g at or Res p o nsi bilities 
T he Pri nci pal I n vesti gat or of a n i n vesti gati o nal site is res p o nsi ble f or e ns uri n g t hat t he st u d y 
is c o n d ucte d i n acc or da nce wit h t he Cli nical St u d y A gree me nt, t he cli nical i n vesti gati o n 
pla n, I S O 1 4 1 5 5, et hical pri nci ples t hat ha ve t heir ori gi ns i n t he Declarati o n of Helsi n ki, a n y 
c o n diti o ns of a p pr o val i m p ose d b y t he re vie wi n g I R B/ E C / R E B, a n d pre vaili n g l ocal a n d/ or 
c o u ntr y la ws a n d/ or re g ulati o ns, w hic he ver aff or ds t he greater pr otecti o n t o t he s u bject.  
T he Pri nci pal I n vesti gat or’s res p o nsi bilities i ncl u de, b ut are n ot li mite d t o, t he f oll o wi n g.  
•  Pri or t o be gi n ni n g t he st u d y , si g n t he Cli nical St u d y A gree me nt a n d c o m pl y wit h t he 
I n vesti gat or res p o nsi bilities as descri be d i n s uc h A gree me nt.   
•  Pr o vi de his/ her q ualificati o ns a n d e x perie nce t o ass u me res p o nsi bilit y f or t he pr o per 
c o n d uct of t he st u d y a n d t hat of ke y me m bers of t he site tea m t hr o u g h u p-t o-date 
c urric ul u m vitae or ot her rele va nt d oc u me ntati o n a n d discl ose p ote ntial c o nflicts of 
i nterest, i ncl u di n g fi na ncial, t hat ma y i nterfere wit h t he c o n d uct of t he cli nical st u d y or 
i nter pretati o n of res ults. 
•  Ma ke n o c ha n ges i n or de viate fr o m t his pr ot oc ol, e xce pt t o pr otect t he life a n d p h ysical 
well -bei n g of a s u bject i n a n e mer ge nc y; d oc u me nt a n d e x plai n a n y de viati o n fr o m t he 
a p pr o ve d pr ot oc ol t hat occ urre d d uri n g t he c o urse of t he cli nical i n vesti gati o n.  
•  Create a n d mai ntai n s o urce d oc u me nts t hr o u g h o ut t he cli nical st u d y a n d e ns ure t heir 
a vaila bilit y wit h direct access d uri n g m o nit ori n g visits or a u dits; e ns ure t hat all cli nical -
i n vesti gati o n-relate d rec or ds are retai ne d per re q uire me nts. 
•  E ns ure t he acc urac y, c o m plete ness, le gi bilit y, a n d ti meli ness of t he data re p orte d t o t he 
s p o ns or i n t he C R Fs a n d i n all re q uire d re p orts. 

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•  Rec or d, re p ort, a n d assess (seri o us ness a n d relati o ns hi p t o t he de vice/ pr oce d ure) e ver y 
a d verse e ve nt as a p plica ble per t he pr ot oc ol  a n d o bser ve d de vice deficie nc y.  
•  Re p ort t o s p o ns or, per t he pr ot oc ol re q uire me nts, all re p orta ble e ve nts. 
•  Re p ort t o t he I R B/ E C / R E B a n d re g ulat or y a ut h orities a n y S A Es a n d de vice deficie ncies 
t hat c o ul d ha ve le d t o a S A D E a n d p ote ntial/ U S A D E or U A D E , if re q uire d b y a p plica ble 
la ws or re g ulati o ns or t his pr ot oc ol or b y t he I R B/ E C/ R E B, a n d s u p pl y B S C wit h a n y 
a d diti o nal re q ueste d i nf or mati o n relate d t o t he safet y re p orti n g of a partic ular e ve nt.  
•  Mai ntai n t he de vice acc o u nta bilit y rec or ds a n d c o ntr ol of t he de vice, e ns uri n g t hat t he 
i n vesti gati o nal de vice is use d o nl y b y a ut h orize d/ desi g nate d users a n d i n acc or da nce wit h 
t his pr ot oc ol a n d i nstr ucti o ns f or use. 
•  All o w t he s p o ns or t o perf or m m o nit ori n g a n d a u diti n g acti vities a n d  be accessi ble t o t he 
cli nical researc h m o nit or or a u dit or a n d res p o n d t o q uesti o ns d uri n g m o nit ori n g visits  or 
a u dit(s) . 
•  All o w a n d s u p p ort re g ulat or y a ut h orities a n d t he I R B/ E C / R E B w he n perf or mi n g a u diti n g 
acti vities. 
•  E ns ure t hat i nf or me d c o nse nt is o btai ne d i n acc or da nce wit h a p plica ble la ws, t his 
pr ot oc ol a n d l ocal I R B/ E C / R E B re q uire me nts. 
•  Pr o vi de a de q uate me dical care t o a s u bject d uri n g a n d after a s u bject’s partici pati o n i n a 
cli nical st u d y i n t he case of a d verse e ve nts, as descri be d i n t he I nf or me d C o nse nt F or m 
(I C F). 
•  I nf or m t he s u bject of t he nat ure a n d p ossi ble ca use of a n y a d verse e ve nts e x perie nce d. 
•  As a p plica ble, pr o vi de t he s u bject wit h necessar y i nstr ucti o ns o n pr o per use, ha n dli n g, 
st ora ge, a n d ret ur n of t he i n vesti gati o nal de vice w he n it is use d/ o perate d b y t he s u bject.  
•  I nf or m t he s u bject of a n y ne w si g nifica nt fi n di n gs occ urri n g d uri n g t he cli nical 
i n vesti gati o n, i ncl u di n g t he nee d f or a d diti o nal me dical care t hat ma y be re q uire d. 
•  Pr o vi de t he s u bject wit h well -defi ne d pr oce d ures f or p ossi ble e mer ge nc y sit uati o ns 
relate d t o t he cli nical st u d y, a n d ma ke t he necessar y arra n ge me nts f or e mer ge nc y 
treat me nt, i ncl u di n g dec o di n g pr oce d ures f or bli n de d/ mas ke d cli nical i n vesti gati o ns, as 
nee d e d. 
•  E ns ure t hat cli nical me dical rec or ds are clearl y mar ke d t o i n dicate t hat t he s u bject is 
e nr olle d i n t his cli nical st u d y.  
•  E ns ure t hat, if a p pr o priate, s u bjects e nr olle d i n t he cli nical i n vesti gati o n are pr o vi de d 
wit h s o me mea ns of s h o wi n g t heir partici pati o n i n t he cli nical i n vesti gati o n, t o get her wit h 
i de ntificati o n a n d c o m plia nce i nf or mati o n f or c o nc o mita nt treat me nt meas ures (c o ntact 
a d dress a n d tele p h o ne n u m bers s hall be pr o vi de d).  
•  I nf or m, wit h t he s u bject’s a p pr o val or w he n re q uire d b y nati o nal re g ulati o ns, t he 
s u bject’s pers o nal p h ysicia n a b o ut t he s u bject’s partici pati o n i n t he cli nical i n vesti gati o n.  

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•  Ma ke all reas o na ble eff orts t o ascertai n t he reas o n(s) f or a s u bject’s pre mat ure 
wit h dra wal fr o m cli nical i n vesti gati o n w hile f ull y res pecti n g t he s u bject’s ri g hts.  
•  E ns ure t hat a n a de q uate i n vesti gati o n site tea m a n d facilities e xist a n d are mai ntai ne d a n d 
d oc u me nte d d uri n g t he cli nical i n vesti gati o n.  
•  Atte m pt t o e nr oll patie nts re prese ntati ve of t he sites o verall patie nt p o p ulati o n.   
All i n vesti gat ors will p r o vi de t heir q ualificati o ns a n d e x perie nce t o ass u me res p o nsi bilit y f or 
t heir dele gate d tas ks t hr o u g h u p-t o-date c urric ul u m vitae or ot her rele va nt d oc u me ntati o n a n d 
discl ose p ote ntial c o nflicts of i nterest, i ncl u di n g fi na ncial, t hat ma y i nterfere wit h t he c o n d uct 
of t he cli nical st u d y or i nter pretati o n of res ults.  
 
1 6. 2. 1.  Dele g ati o n of Res p o nsi bilit y  
W he n s pecific tas ks are dele gate d b y a n i n vesti gat or, i ncl u di n g b ut n ot li mite d t o c o n d ucti n g 
t he i nf or me d c o nse nt pr ocess, t he Pri nci pal I n vesti gat or is res p o nsi ble f or pr o vi di n g 
a p pr o priate trai ni n g , e ns uri n g researc h tea m me m bers are c o m pete nt t o perf or m t he tas ks 
t he y ha ve bee n dele gate d a n d ha ve a de q uate s u per visi o n of t h ose t o w h o m tas ks are 
dele gate d. W here t here is a s u b-i n vesti gat or at a site, t he s u b-i n vesti gat or s h o ul d n ot be 
dele gate d t he pri mar y s u per vis or y res p o nsi bilit y f or t he site.  T he Pri n ci pal In vesti gat or is 
acc o u nta ble f or re g ulat or y vi olati o ns res ulti n g fr o m fail ure t o a de q uatel y s u per vise t he 
c o n d uct of t he cli nical st u d y.  
 I nstit uti o n al Revie w B o ar d/ Et hics C o m mittee 
T he i n vesti gati o nal site will  o btai n t he writte n a n d date d a p pr o val/fa v ora ble o pi ni o n of t he 
I R B/E C/ R E B  f or t he cli nical i n vesti gati o n bef ore recr uiti n g s u bjects a n d i m ple me nti n g all 
s u bse q ue nt a me n d me nts, if re q uire d. 
A c o p y of t he writte n I R B/ E C / R E B a n d/ or c o m pete nt a ut h orit y ( C A) a p pr o val of t he 
pr ot oc ol ( or per missi o n t o c o n d uct t he st u d y) a n d I C F, m ust be recei ve d b y t he s p o ns or 
bef ore recr uit me nt of s u bjects i nt o t he st u d y a n d s hi p me nt of i n vesti gati o nal 
pr o d uct/e q ui p me nt . Pri or a p pr o val m ust als o be o btai ne d f or ot her materials relate d t o s u bject 
recr uit me nt or w hic h will be pr o vi de d t o t he s u bject . 
A n y a me n d me nt t o t he pr ot oc ol will re q uire re vie w a n d a p pr o val b y t he I R B / E C/ R E B bef ore 
t he c ha n ges are i m ple me nte d t o t he st u d y.  All c ha n ges t o t he I C F will be I R B/ E C/ R E B 
a p pr o ve d ; a deter mi nati o n will be ma de re gar di n g w het her a ne w I C F nee ds t o be o btai ne d 
fr o m partici pa nts w h o pr o vi de d c o nse nt , usi n g a pre vi o usl y a p pr o ve d I C F. A n n ual 
I R B/E C / R E B a p pr o val a n d re ne wals will be o btai ne d t hr o u g h o ut t he d urati o n of t he st u d y as 
re q uire d b y a p plica ble l ocal/c o u ntr y la ws or re g ulati o ns or I R B/ E C / R E B re q uire me nts. 
C o pies of t he st u d y re p orts a n d t he I R B/ E C/ R E B c o nti n ua nce of a p pr o val m ust be pr o vi de d 
t o t he s p o ns or.  

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 S p o ns or Res p o nsi bilities  
All i nf or mati o n a n d data se nt t o B S C c o ncer ni n g s u bjects or t heir partici pati o n i n t his st u d y 
will be c o nsi dere d c o nfi de ntial b y B S C  a n d will be ke pt c o nfi de ntial i n acc or da nce wit h all 
a p plica ble la ws a n d re g ulati o ns . O nl y a ut h orize d B S C pers o n nel a n d/or a B S C re prese ntati ve 
i ncl u di n g, b ut n ot li mite d t o C o ntract R esearc h O r ga nizati o n ( C R O), will ha ve access t o t his 
i nf or mati o n. A ut h orize d re g ulat or y pers o n nel ha ve t he ri g ht t o i ns pect a n d c o p y all rec or ds 
perti ne nt t o t his st u d y. St u d y data c ollecte d d uri n g t his st u d y ma y be use d b y B S C f or t he 
p ur p oses of t his st u d y, p u blicati o n, a n d t o s u p p ort f ut ure researc h a n d/ or ot her b usi ness 
p ur p oses , s uc h as o verseei n g a n d i m pr o vi n g t he perf or ma nce of its de vices, ne w me dical 
researc h a n d pr o p osals f or de vel o pi n g ne w me dical pr o d ucts a n d pr oce d ures. All data use d i n 
t he a nal ysis a n d re p orti n g of t his st u d y or s hare d wit h a t hir d -part y researc her will be wit h o ut 
i de ntifia ble refere nce t o s pecific s u bjects. 
I nf or mati o n recei ve d d uri n g t he st u d y will n ot be use d t o mar ket t o s u bjects; s u bject na mes 
will n ot be place d o n a n y maili n g lists or s ol d t o a n y o ne f or mar keti n g p ur p oses.   
 I ns ur a nce  
W here re q uire d b y l ocal/c o u ntr y re g ulati o n, pr o of a n d t y pe of i ns ura nce c o vera ge, b y B S C 
f or s u bjects i n t he st u d y will be o btai ne d. 
1 7.  M o nit ori n g  
M o nit ori n g will be perf or me d d uri n g t he st u d y t o assess c o nti n ue d c o m plia nce wit h t he 
pr ot oc ol a n d a p plica ble re g ulati o ns. I n a d diti o n, t he cli nical researc h m o nit or verifies t hat 
st u d y rec or ds are a de q uatel y mai ntai ne d, t hat data are re p orte d i n a satisfact or y ma n ner wit h 
res pect t o ti meli ness, a de q uac y, a n d acc urac y, a n d t hat t he Pri nci pal I n vesti gat or c o nti n ues t o 
ha ve s ufficie nt staff a n d facilities t o c o n d uct t he st u d y safel y a n d effecti vel y. T he Pri nci pal 
I n vesti gat or/i nstit uti o n g uara ntees direct access t o ori gi nal s o urce d oc u me nts , eit her i n 
electr o nic or pa per f or m, b y B S C pers o n nel, t heir desi g nees, a n d a p pr o priate re g ulat or y 
a ut h orities. 
T he s p o ns or will p ut a pla n i n place t o d oc u me nt t he s pecific m o nit ori n g re q uire me nts. 
T he st u d y ma y als o be s u bject t o a q ualit y ass ura nce a u dit b y B S C or its desi g nees, as well as 
i ns pecti o n b y a p pr o priate re g ulat or y a ut h orities. It is i m p orta nt t hat t he Pri nci pal  I n vesti gat or 
a n d rele va nt st u d y pers o n nel are a vaila ble d uri n g o n -site m o nit ori n g visits or a u dits a n d t hat 
s ufficie nt ti me is de v ote d t o t he pr ocess. 
1 8.  P ote nti al Ris ks a n d Be nefits  
 A ntici p ate d A dverse E ve nts  
P ote ntial  A Es (i n al p ha betical or der) i ncl u de, b ut are n ot li mite d t o t he f oll o wi n g:  
•  Aller gic reacti o n ( de vice, c o ntrast me di u m, me dicati o ns)  

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•  Arr h yt h mias  a n d c o n d ucti o n dist ur ba nces  
•  Car diac ta m p o na de /pericar dial eff usi o n  
•  Deat h  
•  E m b oli zati o n (air, de vice, pla q ue, t hr o m b us, etc.)   
•  He mat o ma  / pse u d oa ne ur ys m/arteri o ve n o us fist ula 
•  Heart Fail ure / v ol u me o verl oa d  
•  He m o d y na mic i nsta bilit y  / car di o ge nic s h oc k/ h y p o-or h y perte nsi o n  
•  He m orr ha ge  
•  M y ocar dial isc he mia / i nfarcti o n 
•  Perc uta ne o us or s ur gical re-i nter ve nti o n 
•  Res pirat or y i ns ufficie nc y  
•  Se psis / i nfecti o n  
•  Sl o w fl o w/ n o refl o w / vasc ular t hr o m b osis 
•  Vas o va gal reacti o ns  
•  Vessel i nj ur y ( dissecti o n, perf orati o n, r u pt ure)  
•  Vessel s pas m  / occl usi o n  
 
P ote ntial a d verse e ve nts n ot ca pt ure d a b o ve, t hat ha ve bee n ass ociate d wit h a d mi nistrati o n of 
paclit a xel at s yste mic d oses , i ncl u de, b ut are n ot li mite d t o, t he f oll o wi n g: 
•  Aller gic/i m m u n ol o gic reacti o n t o dr u g ( paclita xel or str uct urall y -relate d c o m p o u n ds)  
•  Al o pecia  
•  A ne mia  
•  Bl o o d pr o d uct tra nsf usi o n  
•  Gastr oi ntesti nal s y m pt o ms  
•  He mat ol o gic d yscrasia (i ncl u di n g le u k o pe nia, ne utr o pe nia, t hr o m b oc yt o pe nia)  
•  A b n or mal li ver e nz y mes  
•  Hist ol o gic c ha n ges i n vessel wall, i ncl u di n g i nfla m mati o n, cell ular da ma ge or necr osis  
•  M yal gia/ Art hral gia  
•  Peri p heral ne ur o pat h y  
 
T here ma y be ot her p ote ntial a d verse e ve nts t hat are u nf oresee n at t his ti me . A part  
fr o m h y perse nsiti vit y reacti o ns (aller gic/i m m u n ol o gic reacti o ns), t he li keli h o o d of paclita xel -
relate d a d verse e ve nts wit h A ge nt use is l o w d ue t o t he l o w d oses use d o n t he ball o o n w he n 
c o m pare d t o t he s yste mic c he m ot hera pe utic d oses t hese a d verse e ve nts are ass ociate d wit h. 
 
 A ntici p ate d A dverse Device Effects    
T he a ntici pate d a d verse de vice effects ( A D E) ha ve bee n i de ntifie d a n d are liste d i n secti o n 
1 8. 1.  

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 Ris ks Ass oci ate d wit h t he St u dy Device(s)  
T he A ge nt D C B st u d y de vice feat ures a re d uce d paclita xel d ose de nsit y ( 2 μ g/ m m
2) as 
c o m pare d t o m ost c urre ntl y mar kete d D C B pr o d ucts, i ncl u di n g Se Q ue nt Please D C B ( 3 
μ g/ m m 2). T his c oati n g c o m p ositi o n is e x pecte d t o re d uce s yste mic dr u g e x p os ure a n d ma y 
i m pr o ve t he de vice´s safet y pr ofile as j u d ge d fr o m precli nical data [ 3 2]. 
Meta -a nal yses of ra n d o mize d c o ntr olle d trials of paclita xel -c oate d ball o o ns a n d paclita xel -
el uti n g ste nts use d t o treat peri p heral arterial disease i n t he fe m or o p o pliteal arteries ha ve 
i de ntifie d a n i ncrease d ris k of late m ortalit y at 2 years a n d be y o n d. The ma g nit u de a n d 
mec ha nis m f or t he i ncrease d ris k i n m ortalit y is c urre ntl y u nclear. T he a nal yses als o 
de m o nstrate d re d uce d re vasc ularizati o n rates wit h t he dr u g -c o ntai ni n g pr o d ucts. I na de q uate 
i nf or mati o n is a vaila ble t o e val uate t he p ote ntial m ortalit y ris k ass ociate d wit h t he use of 
paclita xel -c oate d de vices f or t he treat me nt of ot her diseases/c o n diti o ns. H o we ver, si milar, 
m ore rece nt meta a nal yses f or de vices use d i n c or o nar y vasc ulat ure di d n ot fi n d a n y m ortalit y 
si g nal f or paclita xel dr u g-c oate d ball oo ns wit h data o ut 3 years.  
 
M ost patie nts t o be e nr olle d i n t his st u d y us uall y ha ve bee n referre d f or eit her  
e n d o vasc ular treat me nt or dia g n ostic i ma gi n g bef ore a treat me nt decisi o n ca n be ma de. I n  
all cases t he treati n g p h ysicia n(s) s hall c o nsi der a n d disc uss alter nati ve treat me nts wit h  
eac h i n di vi d ual patie nt bef ore i nitiati n g scree ni n g a n d e nr ollme nt i nt o t his st u d y. He nce, o nce 
e n d o vasc ular treat me nt wit hi n t his st u d y has bee n i de ntifie d as feasi ble a n d desire d  
m o de of treat me nt, assi g n me nt t o eit her of t he t w o st u d y ar ms will lea d t o treat me nt wit h a  
state-of -t he-art de vice wit h a be neficial ris k be nefit pr ofile. I n ge neral, treat me nt i n t his st u d y 
will f oll o w t he r o uti ne c o urse of c or o nar y vasc ular pr oce d ures.  
 
Patie nts treate d wit h A ge nt are s u bject t o t he sa me ris ks s hare d b y all patie nts u n der g oi n g 
P CI treat me nt. T he ris ks ass ociate d wit h A ge nt are descri be d a n d a nal yze d i n H T Q’s Ris k 
A nal ysis ( R S K 1 1 0 9 1 9 1 7 9a) c o m plia nt wit h I S O 1 4 9 7 1: 2 0 1 2; a n d i ncl u de:  
•  Aller gic reacti o n  
•  E m b olis m   
•  I nfecti o n,  
•  M y ocar dial i nfarcti o n  ( MI) 
•  Necr osis  
•  Reste n osis of treate d se g me nt  
•  T hr o m b osis  
•  Vessel tra u ma ( dissecti o n  /perf orati o n  
•  E x p os ure t o har mf ul material  
•  Pr ol o n ge d pr oce d ure  
•  T o xicit y  
•  A d diti o nal i nter ve nti o n re q uire d  
•  Vessel Occl usi o n / Ac ute rec oil  
•  Str o ke/ TI A  
•  V essel s pas m/ vas os pas m 

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T hese har ms c o ul d p ote ntiall y lea d t o deat h. T he  R is k A nal ysis di d n ot i de ntif y a n y resi d ual 
ris ks a b o ve t he pre defi ne d acce pta nce criteria after i m ple me ntati o n of t he re q uire d 
miti gati o ns.  
 Ris ks ass oci ate d wit h P artici p ati o n i n t he Cli nic al St u dy  
I n a d diti o n t o t he af ore me nti o ne d ris ks ass ociate d wit h t he P CI a n d t he use of paclita xel , use 
of d ual a nti platelet t hera p y i ncrease s t he ris k of blee di n g. T here ma y be a d diti o nal ris ks 
li n ke d t o dr u g c oate d ball o o n t hera p y  w hic h are u nf oresee n at t his ti me  
 Ris k Mi ni miz ati o n Acti o ns  
A d diti o nal ris ks ma y e xist. Ris ks ca n be mi ni mize d t hr o u g h strict c o m plia nce wit h t his 
pr ot oc ol, perf or mi n g pr oce d ures i n t he a p pr o priate h os pital e n vir o n me nt, a d here nce t o 
s u bject selecti o n criteria, a d here nce t o a de q uate lesi o n pre parati o n a n d cl ose m o nit ori n g of 
t he s u bject's p h ysi ol o gic stat us d uri n g t he researc h pr oce d ure a n d/ or f oll o w-u p a n d b y 
pr o m ptl y s u p pl yi n g B S C  wit h all perti ne nt i nf or mati o n re q uire d b y t his pr ot oc ol.  
 A ntici p ate d Be nefits  
C o nte m p orar y i nter ve nti o nal car di ol o g y literat ure re p orts n u mer o us  p ote ntial a d va nta ges of 
n o n -ste nt-base d l ocal dr u g deli ver y via D C B .   
W he n c o m pare d wit h u nc oate d ball o o n a n gi o plast y, D C B is a ntici pate d t o ha ve t he sa me 
a d va nta ges as D E S o ver B M S .  A nti pr oliferati ve dr u g deli ver y  directl y t o t he tar get lesi o n is 
e x pecte d t o re d uce vasc ular s m o ot h m uscle pr oliferati o n a n d c o nse q ue ntl y  t he rate of 
reste n osis.  
Dr u g deli ver y via D C B c o ul d als o all o w m ore  h o m o ge n o us dr u g tra nsfer t o t he disease d 
vessel wall as o p p ose d t o t he areas directl y c o ntacte d  b y a c oate d ste nt str ut. T he e n ha nce d 
u nif or mit y  of deli ver y c o ul d als o e n ha nce dr u g  efficac y. D r u g c o nce ntrati o ns i n t he vessel 
wall wit h D C B are hi g hest j ust after ball o o n i nj ur y, w he n t he ne oi nti mal pr ocess is t he m ost 
vi g or o us. After  dr u g a bs or pti o n t o q uell t he reste n otic pr ocess , t he a bse nce of dr u g, p ol y mer  
a n d metal  use d i n c or o nar y ste nts c o ul d facilitate earlier re-e n d ot helializati o n, p ote ntiall y  
re d uci n g t he ris k of late a n d ver y late t hr o m b osis.  
O b viati n g t he nee d f or a n a d diti o nal la yer of metal t o treat a reste n otic lesi o n ma y be 
partic ularl y be neficial w he n treati n g s mall vessels. A n ot her a d va nta ge of D C B o ver D E S is 
t he re d uce d d urati o n of D A P T re q uire d wit h D C B t hat c o ul d p ossi bl y  res ult i n a re d uce d rate 
of me dicati o n -relate d blee di n g c o m plicati o ns. A d diti o na ll y, t he a bse nce of a metal str uct ure  
all o ws c o nf or mati o n t o  t he ori gi nal arterial  a nat o m y; a critical c o nsi derati o n w he n treati n g  
s mall vessel a n d bif urcati o n lesi o ns. T he a bse nce of a p er ma ne nt pr ost hesis als o re d uces t he 
p ote ntial f or c o m plicati o ns d uri n g f ut ure  e n d o vasc ular pr oce d ures (s h o ul d t he y be re q uire d).  

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 Ris k t o Be nefit R ati o n ale  
Re p orte d be nefits ass ociate d wit h t he use of D C B i ncl u de 1) h o m o ge n o us, l ocal dr u g 
deli ver y; 2) a v oi da nce of per ma ne nt bi o pr ost hesis or f orei g n material i m pla nt; 3) 
re peata bilit y of t he i nter ve nti o n; 4) res pect of t he ori gi nal a nat o m y a n d 5) t he be nefits of a 
l o wer reste n osis rate w he n c o m pare d wit h u nc oate d ball o o n/ste nt t hera p y. 
 
Dr u g deli ver y wit h a ball o o n i nstea d of a ste nt all o ws m ore h o m o ge n o us dr u g tra nsfer t o t he 
vessel wall, as o p p ose d t o, t he li mite d area directl y c o ntacte d b y ste nt str uts. Efficie nt dr u g 
deli ver y will re d uce vasc ular s m o ot h m uscle cell pr oliferati o n (rest e n osis), w hile  all o wi n g 
earlier heali n g of t he e n d ot helial la yer. T he a bse nce of per ma ne nt bi o pr ost hesis or i m pla nt 
ma y als o ma ke f ut ure re vasc ularizati o n eff orts less c o m plicate d.  
 
C o m paris o n of data fr o m A G E N T I D E wit h e xisti n g cli nical data, will c o ntri b ute t o a n 
u n dersta n di n g of t he perf or ma nce a n d safet y of D C B i n patie nts wit h  c or o nar y I S R.  
 
T he A ge nt D C B is e x pecte d t o be s uita ble f or its i nte n de d p ur p ose. T here are n o 
u nacce pta ble resi d ual ris ks/i nt olera ble ris ks a n d all a p plica ble ris ks ha ve bee n a d dresse d 
t hr o u g h t he pr o visi o n of a p pr o priate Directi o ns f or Use. E val uati o n of t he ris ks a n d be nefits 
t hat are e x pecte d t o be ass ociate d wit h use of t he A ge nt D C B de m o nstrate t hat w he n use d 
u n der t he c o n diti o ns i nte n de d, t he be nefits ass ociate d wit h  use of A ge nt D C B s h o ul d 
o ut wei g h t he ris ks.  
1 9.  S afet y Re p orti n g  
 Re p ort a ble Eve nts  by i nvesti g ati o n al site t o B ost o n Scie ntific  
It is t he res p o nsi bilit y of t he i n vesti gat or t o assess a n d re p ort t o B S C a n y e ve nt w hic h occ urs 
i n a n y of f oll o wi n g cate g ories: 
•  All Seri o us A d verse E ve nts  ( S A E)  
•  All C E C e ve nts i ncl usi ve of deat h, MI * , T V R a n d ste nt t hr o m b osis 
•  All A d verse E ve nts (t hr o u g h 1 2 m o nt hs)  
•  All A d verse De vice Effects ( A D E)  (t hr o u g h 1 2 m o nt hs) 
•  All I n vesti gati o nal De vice Deficie ncies  
•  U na ntici pate d A d verse De vice Effects  
•  Ne w fi n di n gs/ u p dates i n relati o n t o alrea d y re p orte d e ve nts  
 
If pre-pr oce d ure car diac e nz y mes were n ot dra w n, b ut t he e ve nt ot her wise meets t he pr ot oc ol 
defi niti o n of MI, t he e ve nt s h o ul d be re p orte d as a n MI f or C E C a dj u dicati o n.    
W he n p ossi ble, t he me dical dia g n osis s h o ul d be re p orte d as t he E ve nt Ter m i nstea d of 
i n di vi d ual s y m pt o ms. 

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If it is u nclear w het her or n ot a n e ve nt fits o ne of t he a b o ve cate g ories, or if t he e ve nt ca n n ot 
be is olate d fr o m t he de vice or pr oce d ure, it s h o ul d be s u b mitte d as a n a d verse e ve nt a n d/ or 
de vice deficie nc y.  
A n y re p orta ble, e x perie nce d b y t he st u d y s u bject after i nf or me d c o nse nt a n d o nce c o nsi dere d 
e nr olle d i n t he st u d y (as defi ne d i n st u d y s u bject classificati o n secti o n), w het her pri or t o, 
d uri n g or s u bse q ue nt t o t he st u d y pr oce d ure, m ust be rec or de d i n t he e C R F.  
U n derl yi n g diseases a n d c hr o nic c o n diti o ns are n ot re p orte d as A Es u nless t here is a n 
i ncrease i n se verit y or fre q ue nc y d uri n g t he c o urse of t he i n vesti gati o n. Deat h s h o ul d n ot be 
rec or de d as a n A E b ut  s h o ul d o nl y be reflecte d as a n o utc o me of o ne ( 1) s pecific S A E (Ta ble 
1 9. 2 -1  Ta ble 1 9. 2 -1 : Safet y Defi niti o ns  f or A E defi niti o ns). 
Refer t o Secti o n 1 8 f or t he k n o w n ris ks ass ociate d wit h t he st u d y de vice(s).  
I n-patie nt h os pitalizati o n is defi ne d as t he s u bjects bei n g a d mitte d t o t he h os pital, wit h t he 
f oll o wi n g e xce pti o ns. 
•  A h os pitalizati o n t hat is u nc o m plicate d a n d electi ve/ pla n ne d (i.e., pla n ne d pri or t o 
e nr oll me nt) d oes n ot ha ve t o be re p orte d as a n S A E.  
•  If c o m plicati o ns or e ve nts occ ur d uri n g a n electi ve/ pla n ne d (i.e., pla n ne d pri or t o 
e nr oll me nt) h os pitalizati o n after e nr oll me nt, t he c o m plicati o ns a n d e ve nt A Es m ust be 
re p orte d if t he y meet t he pr ot oc ol-s pecifie d defi niti o ns. H o we ver, t he ori gi nal 
electi ve/ pla n ne d h os pitalizati o n(s) itself s h o ul d n ot be re p orte d as a n S A E.  
 
 Defi niti o ns a n d Cl assific ati o n  
A d verse e ve nt defi niti o ns are pr o vi de d i n  Ta ble 1 9. 2 -1 . A d mi nistrati ve e dits were ma de o n 
t he safet y defi niti o n s fr o m a p plica ble re g ulati o ns a n d g ui d a nce i ncl u di n g ( b ut n ot li mite d t o) 
2 1 C F R Part 8 1 2, I S O 1 4 1 5 5 a n d E U M D R 2 0 1 7/ 7 4 5/ M D C G 2 0 2 0 -1 0/ 1 G ui da nce o n Safet y 
Re p orti n g i n Cli nical I n vesti gati o ns  f or clarificati o n p ur p oses. 
 
T a ble 1 9. 2 -1 : S afet y Defi niti o ns  
Ter m  
Defi niti o n  
A d verse E ve nt ( A E)  
 
Ref: I S O 1 4 1 5 5  
 
Ref: M D C G 2 0 2 0 -1 0/ 1   
 
 
 
 
A n y u nt o war d me dical occ urre nce, u ni nte n de d disease or i nj ur y, or a n y 
u nt o war d cli nical si g ns (i ncl u di n g a n a b n or mal la b orat or y fi n di n g) i n 
s u bjects, users or ot her pers o ns, i n t he c o nte xt of a cli nical i n vesti gati o n, 
w het her or n ot relate d t o t he i n vesti gati o nal me dical de vice  a n d w het her 
a ntici pate d or u na ntici pate d .  
N O T E 1 : T his i ncl u des e ve nts relate d t o t he i n vesti gati o nal me dical 
de vice or c o m parat or.  
N O T E 2 : T his defi niti o n i ncl u des e ve nts relate d t o t he pr oce d ures 
i n v ol ve d. 
N O T E 3 : F or users or ot her pers o ns, t his defi niti o n is restricte d t o e ve nts 
relate d t o t he i n vesti gati o nal me dical de vice.  
A d verse De vice Effect ( A D E)  
 
A d verse e ve nt relate d t o t he use of a n i n vesti gati o nal me dical de vice  

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T a ble 1 9. 2 -1 : S afet y Defi niti o ns  
Ter m  
Defi niti o n  
Ref: I S O 1 4 1 5 5  
 
Ref: M D C G 2 0 2 0 -1 0/ 1   
N O T E 1 : T his  i ncl u des a n y a d verse e ve nt res ulti n g fr o m i ns ufficie ncies 
or i na de q ua cies i n t he i nstr ucti o ns f or use, t he de pl o y me nt, t he 
i m pla ntati o n, t he i nstallati o n, t he o perati o n, or a n y malf u ncti o n of t he 
i n vesti gati o nal me dical de vice. 
N O T E 2 : T his defi niti o n i ncl u des a n y e ve nt res ulti n g fr o m use err or or 
fr o m i nte nti o nal mis use of t he i n vesti gati o nal me dical de vice.  
N O T E 3 : T his i ncl u des ‘c o m parat or’ if t he c o m parat or is a me dical 
de vice.  
Seri o us A d verse E ve nt ( S A E)  
 
Ref: I S O 1 4 1 5 5  
 
Ref: M D C G 2 0 2 0 -1 0/ 1   
A d verse e ve nt t hat  le d t o a n y of t he f oll o wi n g: 
a) deat h , 
b)  seri o us deteri orati o n i n t he healt h of t he s u bject , users or ot her pers o ns 
as defi ne d b y  eit her: 
1)  a life-t hreate ni n g ill ness or i nj ur y, or 
2)  a per ma ne nt i m pair me nt of a b o d y str uct ure or a b o d y f u ncti o n, 
i ncl u di n g c hr o nic diseases, or  
3)  i n-patie nt h os pitalizati o n or pr ol o n g ati o n of e xisti n g  
h os pitalizati o n , or 
4)  me dical or s ur gical i nter ve nti o n t o pre ve nt life -t hreate ni n g ill ness 
or  i nj ur y or per ma ne nt i m pair me nt t o a b o d y str uct ure or a b o d y 
f u ncti o n 
c) fetal distress, fetal deat h, or a c o n ge nital a b n or malit y or birt h defect 
i ncl u di n g p h ysical or me ntal i m pair me nt 
N O T E 1 : Pla n ne d h os pitalizati o n  f or a pre-e xisti n g c o n diti o n, or a 
pr oce d ure re q uire d b y t he cli nical i n vesti gati o nal pla n, wit h o ut a seri o us 
deteri orati o n i n healt h, is n ot c o nsi dere d a seri o us a d verse e ve nt.  
Seri o us A d verse De vice Effect 
( S A D E) 
 
Ref: I S O 1 4 1 5 5  
 
Ref: M E D D E V 2. 7/ 3  
A d verse de vice effect t hat has res ulte d i n a n y of t he c o nse q ue nces 
c haracteristic of a seri o us a d verse e ve nt.  
 
U na ntici pate d A d verse De vice 
Effect ( U A D E)  
 
Ref: 2 1 C F R P art 8 1 2  
 
 
A n y seri o us a d verse effect o n healt h or safet y or a n y life -t hreate ni n g 
pr o ble m or deat h ca use d b y, or ass ociate d wit h, a de vice, if t hat effect, 
pr o ble m, or deat h was n ot pre vi o usl y i de ntifie d i n nat ure, se verit y, or 
de gree of i nci de nce i n t he i n vesti gati o nal pla n or a p plicati o n (i ncl u di n g a 
s u p ple me ntar y pla n or a p plicati o n), or a n y ot her u na ntici pate d seri o us 
pr o ble m ass ociate d wit h a de vice t hat relates t o t he ri g hts, safet y, or 
welfare of s u bjects.   
Seri o us Healt h T hreat  
 
Ref: I S O 1 4 1 5 5  
 
Si g nal fr o m a n y a d verse e ve nt or de vice deficie nc y t hat i n dicates a n 
i m mi ne nt ris k of deat h or a seri o us deteri orati o n i n t he healt h i n s u bjects, 
users or ot her pers o ns, a n d t hat re q uires pr o m pt re me dial acti o n  
f or ot her s u bjects, users or ot her pers o ns. 
N ote 1: T his w o ul d i ncl u de e ve nts t hat are of si g nifica nt a n d u ne x pecte d 
nat ure s uc h t hat t he y bec o me alar mi n g as a p ote ntial seri o us healt h hazar d 
or p ossi bilit y of m ulti ple deat hs occ urri n g at s h ort i nter vals.  

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T a ble 1 9. 2 -1 : S afet y Defi niti o ns  
Ter m  
Defi niti o n  
De vice Deficie nc y  
 
Ref: I S O 1 4 1 5 5  
 
Ref: M D C G 2 0 2 0 -1 0/ 1   
A n  ina de q uac y of a  me dical de vice relate d t o its i de ntit y, q ualit y, 
d ura bilit y, relia bilit y, usa bilit y, safet y or perf or ma nce. N O T E 1 : De vice 
deficie ncies i ncl u de malf u ncti o ns, use err ors, a n d i na de q uac y i n t he 
i nf or mati o n s u p plie d b y t he ma n ufact urer i ncl u di n g la belli n g.  
N O T E 2 : T his defi niti o n i ncl u des de vice deficie ncies relate d t o t he 
i n vesti gati o nal me dical de vice [or t he c o m parat or ]. 
 
T he f oll o wi n g defi niti o ns will be use d f or defi ni n g h os pitalizati o n or pr ol o n gati o n of h os pitalizati o n f or S A E 
classificati o n p ur p oses:  
H os pitalizati o ns  
H os pitalizati o n d oes n ot i ncl u de:  
•   e mer ge nc y r o o m visit t hat d oes n ot res ult i n i n -patie nt a d missi o n  
N ote: alt h o u g h a n e mer ge nc y r o o m visit d oes n ot itself meet t he 
defi niti o n f or h os pitalizati o n, it ma y meet ot her seri o us criteria 
(e. g. me dical or s ur gical i nter ve nti o n t o pre ve nt per ma ne nt 
i m pair me nt or da ma ge) 
•   electi ve a n d pre -pla n ne d treat me nt/s ur ger y f or a pre -e xisti n g 
c o n diti o n t hat is d oc u me nte d i n t he s u bject’s rec or d at t he ti me of 
c o nse nt/e nr oll me nt  
•   a d missi o n f or s ocial reas o ns a n d/ or res pite care i n t he a bse nce of 
a n y deteri orati o n i n t he s u bject’s ge neral c o n diti o n  (e. g. s u bject is 
h o meless, care gi ver relief)  
pre -pla n ne d, pr ot oc ol -s pecifie d a d missi o n relate d t o t he cli nical st u d y (e. g. 
pr oce d ure re q uire d b y pr ot oc ol)  
Pr ol o n gati o n of  h os pitalizati o n  
I n-patie nt a d missi o n t o t he h os pital t hat is pr ol o n ge d be y o n d t he e x pecte d 
sta n dar d d urati o n f or t he c o n diti o n u n der treat me nt. 
N ote: ne w a d verse e ve nts occ urri n g d uri n g t he h os pitalizati o n are 
e val uate d t o deter mi ne if t he y pr ol o n ge d h os pitalizati o n or meet a n ot her 
S A E criteria.  
 
 
 Rel ati o ns hi p  t o St u dy Device(s)a n d / or St u dy Pr oce d ure  
T he I n vesti gat or m ust assess t he relati o ns hi p of t he re p orta ble A E t o t he st u d y de vice (s) a n d/ 
or st u d y pr oce d ure . See criteria i n Ta ble 1 9. 3 -1 .  
T a ble 1 9. 3 -1 : Criteri a f or Assessi n g Rel ati o ns hi p of St u d y De vice(s) or Pr oce d ure  t o 
A d verse E ve nt  
Cl assific ati o n  
Descri pti o n  
N ot R el ate d 
Ref: M D C G 2 0 2 0 -1 0/ 1  
Relati o ns hi p t o t he de vice , c o m parat or or pr oce d ures ca n be e xcl u de d w he n:  
- t he e ve nt has n o te m p oral relati o ns hi p wit h t he use of t he i n vesti gati o nal de vice or 
t he pr oce d ures relate d t o t he use of t he i n vesti gati o nal de vice; 

F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A Q  
         C o nfi de ntial   
        A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 6 4  of 9 0  
 
  
T a ble 1 9. 3 -1 : Criteri a f or Assessi n g Rel ati o ns hi p of St u d y De vice(s) or Pr oce d ure  t o 
A d verse E ve nt  
Cl assific ati o n  
Descri pti o n  
- t he seri o us e ve nt d oes n ot f oll o w a k n o w n res p o nse patter n t o t he me dical de vice 
(if t he res p o nse patter n is pre vi o usl y k n o w n) a n d is bi ol o gicall y i m pla usi ble; 
- t he disc o nti n uati o n of me dical de vice a p plicati o n or t he re d ucti o n of t he le vel of 
acti vati o n/e x p os ure - w he n cli nicall y feasi ble –  a n d rei ntr o d ucti o n of its use ( or 
i ncrease of t he le vel of acti vati o n/e x p os ure), d o n ot i m pact o n t he seri o us e ve nt; 
- t he e ve nt i n v ol ves a b o d y-site or a n or ga n t hat ca n n ot be affecte d b y t he de vice or 
pr oce d ure;  
- t he seri o us e ve nt ca n be attri b ute d t o a n ot her ca use (e. g. a n u n derl yi n g 
or c o nc urre nt ill ness/ cli nical c o n diti o n, a n effect of a n ot her de vice, dr u g, treat me nt 
or ot her ris k fact ors);  
- t he e ve nt d oes n ot de pe n d o n a false res ult gi ve n b y t he i n vesti gati o nal de vice 
use d f or dia g n osis, w he n a p plica ble; - I n or der t o esta blis h t he n o n-relate d ness, n ot 
all t he criteria liste d a b o ve mi g ht be met at t he sa me ti me, de pe n di n g o n t he t y pe of 
de vice/ pr oce d ures a n d t he seri o us e ve nt.  
P ossi bl y Rel ate d  
Ref: M D C G 2 0 2 0 -1 0/ 1  
T he relati o ns hi p wit h t he use of t he i n vesti gati o nal de vice or c o m parat or, or t he 
relati o ns hi p wit h pr oce d ures is wea k b ut ca n n ot be r ule d o ut c o m pletel y. 
Alter nati ve ca uses are als o p ossi ble (e. g. a n u n derl yi n g or c o nc urre nt ill ness/ 
cli nical c o n diti o n or/a n d a n effect of a n ot her de vice, dr u g or treat me nt). Cases were 
relate d ness ca n n ot be assesse d or n o i nf or matio n has bee n o btai ne d s h o ul d als o be 
classifie d as p ossi ble. 
Pr o b a bl y Rel ate d  
Ref: M D C G 2 0 2 0 -1 0/ 1  
T he relati o ns hi p wit h t he use of t he i n vesti gati o nal de vice  or , c o m parat or, or t he 
relati o ns hi p wit h pr oce d ures see ms rele va nt a n d/ or t he e ve nt ca n n ot be reas o na bl y 
e x plai ne d b y a n ot her ca use.  
C a us al Rel ati o ns hi p  
Ref: M D C G 2 0 2 0 -1 0/ 1  
T he seri o us e ve nt is ass ociate d wit h t he i n vesti gati o nal de vice  or c o m parat or or  
wit h pr oce d ures be y o n d reas o na ble d o u bt w he n:  
- t he e ve nt is a k n o w n si de effect of t he pr o d uct cate g or y t he de vice bel o n gs t o or 
of si milar de vices a n d pr oce d ures;  
- t he e ve nt has a te m p oral relati o ns hi p wit h i n vesti gati o nal de vice use/a p plicati o n 
or pr oce d ures;  
- t he e ve nt i n v ol ves a b o d y-site or or ga n t hat 
-t he i n vesti gati o nal de vice or pr oce d ures are a p plie d t o;-t he i n vesti gati o nal 
de vice or pr oce d ures ha ve a n effect o n;  
- t he seri o us e ve nt f oll o ws a k n o w n res p o nse patter n t o t he me dical de vice (if t he 
res p o nse patter n is pre vi o usl y k n o w n); 
- t he disc o nti n uati o n of me dical de vice a p plicati o n ( or re d ucti o n of t he le vel of 
acti vati o n/e x p os ure) a n d rei ntr o d ucti o n of its use ( or i ncrease of t he le vel of 
acti vati o n/e x p os ure), i m pact o n t he seri o us e ve nt ( w he n cli nicall y feasi ble);  
- ot her p ossi ble ca uses (e. g. a n u n derl yi n g or c o nc urre nt ill ness/ cli nical c o n diti o n 
or/a n d a n effect of a n ot her de vice, dr u g or treat me nt) ha ve bee n a de q uatel y r ule d 
o ut;  
- har m t o t he s u bject is d ue t o err or i n use;  
- t he e ve nt de pe n ds o n a false res ult gi ve n b y t he i n vesti gati o nal de vice use d f or 
dia g n osis, w he n a p plica ble;  

F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A Q  
         C o nfi de ntial   
        A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 6 5  of 9 0  
 
  
T a ble 1 9. 3 -1 : Criteri a f or Assessi n g Rel ati o ns hi p of St u d y De vice(s) or Pr oce d ure  t o 
A d verse E ve nt  
Cl assific ati o n  
Descri pti o n  
- I n or der t o esta blis h t he relate d ness, n ot all t he criteria liste d a b o ve mi g ht be met 
at t he sa me ti me, de pe n di n g o n t he t y pe of de vice/ pr oce d ures a n d t he seri o us e ve nt.  
 
 I nvesti g at or Re p orti n g Re q uire me nts 
T he c o m m u nicati o n re q uire me nts f or re p orti n g t o B S C are as s h o w n i n Ta ble 1 9. 4 -1 . 
T a ble 1 9. 4 -1 : I n vesti g at or Re p orti n g Re q uire me nts 
E ve nt Cl assific ati o n  
C o m m u nic ati o n Met h o d   
C o m m u nic ati o n Ti meli ne pre -m ar ket st u dies  
(2 1 C F R Part 8 1 2, M D C G 2 0 2 0 -1 0/ 1   
) 
U na ntici pate d A d verse De vice 
Effect / U na ntici pate d Seri o us 
A d verse De vice Effect  
 
C o m plete A E e C R F pa ge 
wit h all a vaila ble ne w a n d 
u p date d i nf or mati o n .  
 
•   Wit hi n 1 b usi ness da y of first bec o mi n g 
a ware of t he e ve nt.  
•   Ter mi nati n g at t he e n d of t he st u d y  
Pr o vi de all rele va nt s o urce 
d oc u me ntati o n ( de -
i de ntifie d/ pse u d o n y mize d) 
f or re p orte d e ve nt.  
•   At re q uest of s p o ns or.  
Seri o us A d verse E ve nt    
C o m plete A E e C R F pa ge 
wit h all a vaila ble ne w a n d 
u p date d i nf or mati o n .  
•   I m me diatel y, b ut n ot later t ha n 3 cale n dar 
da ys of first bec o mi n g a ware o f t he e ve nt 
or as per l ocal/re gi o nal re g ulati o ns .  
•   Re p orti n g re q uire d t hr o u g h t he e n d of t he 
st u d y 
Pr o vi de all rele va nt s o urce 
d oc u me ntati o n ( de -
i de ntifie d/ pse u d o n y mize d) 
f or re p orte d e ve nt. 
•   U p o n re q uest of s p o ns or 
Seri o us A d verse De vice Effects  
 
C o m plete A E e C R F pa ge 
wit h all a vaila ble ne w a n d 
u p date d i nf or mati o n . 
•   I m me diatel y, b ut n ot later t ha n 3 cale n dar da ys 
of first bec o mi n g a ware  of t he e ve nt or as per 
l ocal/re gi o nal re g ulati o ns.  
•   Re p orti n g re q uire d t hr o u g h t he e n d of t he st u d y  
Pr o vi de all rele va nt s o urce 
d oc u me ntati o n ( de -
i de ntifie d/ pse u d o n y mize d) 
f or re p orte d e ve nt.  
•   W he n d oc u me ntati o n is a vaila ble  
•   U p o n s p o ns or re q uest.  
De vice Deficie ncies  (i ncl u di n g 
b ut n ot li mite d t o  m alf u ncti o ns,  
use err ors  a n d i na de q uac y i n 
i nf or mati o n s u p plie d b y t he 
C o m plete  De vice 
Deficie ncies C R F wit h all 
availa ble ne w a n d u p date d 
i nf or mati o n.  
•   I m me diatel y, b ut n ot later t ha n 3 
cale n dar da ys of first bec o mi n g a ware 
of t he e ve nt .  
•   Re p orti n g re q uire d t hr o u g h t he e n d of 
t he st u d y 

F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A Q  
         C o nfi de ntial   
        A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 6 6  of 9 0  
 
  
T a ble 1 9. 4 -1 : I n vesti g at or Re p orti n g Re q uire me nts 
E ve nt Cl assific ati o n  
C o m m u nic ati o n Met h o d   
C o m m u nic ati o n Ti meli ne pre -m ar ket st u dies  
(2 1 C F R Part 8 1 2, M D C G 2 0 2 0 -1 0/ 1   
) 
ma n ufact urer, i ncl u di n g 
la beli n g) 
N ote:  A n y De vice Deficie nc y 
t hat mi g ht ha ve le d t o a seri o us 
a d verse e ve nt if a p pr o priate 
acti o n ha d n ot bee n ta ke n , 
i nter ve nti o n ha d n ot occ urre d,  
circ u msta nces ha d bee n less 
f ort u nate is c o nsi dere d a 
re p orta ble e ve nt. 
Pr o vi de all rele va nt s o urce 
d oc u me ntati o n ( de -
i de ntifie d/ pse u d o n y mize d) 
f or re p orte d e ve nt. 
•   At re q uest of s p o ns or  
A d verse E ve nt  i ncl u di n g 
A d verse De vice Effects  
C o m plete A E e C R F pa ge, 
w hic h c o ntai ns s uc h 
i nf or mati o n as date of A E, 
treat me nt of A E res ol uti o n, 
assess me nt of seri o us ness 
a n d relati o ns hi p t o t he 
de vice .  
•   I n a ti mel y ma n ner b ut n ot later t ha n 1 0 
b usi ness da ys  after bec o mi n g a ware of 
t he i nf or mati o n 
•   At s p o ns or re q uest  
•   A Es a n d A D Es will o nl y be c ollecte d 
t hr o u g h 1 2 m o nt h f oll o w u p  
Pr o vi de all rele va nt s o urce 
d oc u me ntati o n ( de -
i de ntifie d/ pse u d o n y mize d) 
f or re p orte d e ve nt.  
*  Please n ote t hat pre -mar ket st u dies are cli nical st u dies wit h i n vesti gati o nal de vices or wit h me dical de vices t hat bear 
t he re g ulat or y a p pr o val a n d are n ot bei n g use d f or t he sa me a p pr o ve d i n dicati o ns. 
 Device Deficie ncies  
All A G E N T D C B d e vice deficie ncies will be c ollecte d a n d will be d oc u me nte d a n d  re p orte d 
t o B S C. If p ossi ble, t he de vice (s) s h o ul d be ret ur ne d t o B S C f or a nal ysis. I nstr ucti o ns f or 
ret ur ni n g t he i n vesti gati o nal de vice(s) will be pr o vi de d i n t he M O P. If it is n ot p ossi ble t o 
ret ur n t he de vice, t he i n vesti gat or s h o ul d d oc u me nt w h y t he de vice was n ot ret ur ne d a n d t he 
fi nal dis p ositi o n of t he de vice.  De vice fail ures a n d malf u ncti o ns s h o ul d als o be d oc u me nte d 
i n t he s u bject’s me dical rec or d.  
De vice deficie ncies (i ncl u di n g b ut n ot li mite d t o fail ures, malf u ncti o ns, a n d pr o d uct 
n o nc o nf or mities) are n ot a d verse e ve nts; t he y s h o ul d be re p orte d o n t he a p pr o priate e C R F 
per t he st u d y C R F C o m pleti o n G ui deli nes.  If a n a d verse e ve nt res ults fr o m a de vi ce fail ure 
or malf u ncti o n, t he A E s h o ul d be rec or de d as a n a d verse e ve nt o n t he a p pr o priate e C R F if it 
meets t he pr ot oc ol -s pecifie d defi niti o n of a re p orta ble e ve nt. 
A n y De vice Deficie nc y t hat mi g ht ha ve le d t o a seri o us a d verse e ve nt if a) s uita ble acti o n 
ha d n ot bee n ta ke n or b) i nter ve nti o n ha d n ot bee n ma de or c) if circ u msta nces ha d bee n less 
f ort u nate is c o nsi dere d a re p orta ble e ve nt.  

F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A Q  
         C o nfi de ntial   
        A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 6 7  of 9 0  
 
  
 Re p orti n g t o Re g ul at ory A ut h orities / I R Bs / E Cs / R E Bs/ I nvesti g at ors 
B S C is res p o nsi ble f or re p orti n g a d verse e ve nt i nf or mati o n t o all partici pati n g Pri nci pal 
In vesti gat ors , I R Bs/ E Cs/ R E Bs a n d re g ulat or y a ut h orities, as a p plica ble.  
T he Pri nci pal I n vesti gat or is res p o nsi ble f or i nf or mi n g t he I R B/ E C/ R E B, a n d re g ulat or y 
a ut h orities of U A D E s a n d S A Es as re q uire d b y l ocal /re gi o nal re g ulati o ns. 
2 0.  I nf or me d C o nse nt 
S u bject partici pati o n i n t his cli nical st u d y is v ol u ntar y.  Writte n I nf or me d C o nse nt is re q uire d 
fr o m eac h s u bject or his/ her le gall y a ut h orize d re prese ntati ve . T he I n vesti gat or is res p o nsi ble 
f or e ns uri n g t hat I nf or me d C o nse nt is o btai ne d pri or t o t he use of a n y i n vesti gati o nal de vices, 
st u d y-re q uire d pr oce d ures a n d/ or testi n g, or data c ollecti o n.  
T he o btai ni n g a n d d oc u me ntati o n of I nf or me d C o nse nt m ust be i n acc or da nce wit h t he 
pri nci ples of t he Declarati o n of Helsi n ki, I S O 1 4 1 5 5, a n y a p plica ble nati o nal re g ulati o ns, a n d 
l ocal Et hics C o m mittee a n d/ or Re g ulat or y a ut h orit y, as a p plica ble. T he I C F m ust be acce pte d  
b y B S C or it s dele gate (e. g. C R O) a n d a p pr o ve d b y t he site’s I R B/ E C/ R E B, or ce ntral I R B, if 
a p plica ble. 
B ost o n Scie ntific will pr o vi de a st u d y -s pecific te m plate of t he I C F t o i n vesti gat ors 
partici pati n g i n t his st u d y. T he I C F te m plate ma y be m o difie d t o meet t he re q uire me nts of t he 
i n vesti gati ve site’s I R B/ E C/ R E B.  A n y m o dificati o n re q uires acce pta nce fr o m B S C pri or t o 
use of t he f or m.  T he I C F m ust be i n a la n g ua ge u n dersta n da ble t o t he s u bject a n d if nee de d, 
B S C will assist t he site i n o btai ni n g a writte n c o nse nt tra nslati o n. Tra nslate d c o nse nt f or ms 
m ust als o ha ve I R B/ E C / R E B a p pr o val pri or t o t heir use.  Pri vac y la n g ua ge s hall be i ncl u de d 
i n t he b o d y of t he f or m or as a se parate f or m as a p plica ble.   
T he pr ocess of o btai ni n g I nf or me d C o nse nt s hall  at a mi ni m u m i ncl u de t he f oll o wi n g ste ps, 
as well as a n y ot her ste ps re q uire d b y a p plica ble la ws, r ules, re g ulati o ns a n d g ui deli nes : 
•  be c o n d ucte d b y t he Pri nci pal I n vesti gat or or desi g nee a ut h orize d t o c o n d uct t he pr ocess,  
•  i ncl u de a descri pti o n of all as pects of t he cli nical st u d y t hat are rele va nt t o t he s u bject’s 
decisi o n t o partici pate t hr o u g h o ut t he cli nical st u d y,  
•  a v oi d a n y c oerci o n of or u n d ue i nfl ue nce of s u bjects t o partici pate,  
•  n ot wai ve or a p pear t o wai ve s u bject’s le gal ri g hts,  
•  use nati ve la n g ua ge t hat is n o n -tec h nical a n d u n dersta n da ble t o t he s u bject or his/ her 
le gal re prese ntati ve, 
•  pr o vi de a m ple ti me f or t he s u bject t o c o nsi der partici pati o n a n d as k q uesti o ns if 
necessar y,  
•  e ns ure i m p orta nt ne w i nf or mati o n is pr o vi de d t o ne w a n d e xisti n g s u bjects t hr o u g h o ut t he 
cli nical st u d y.  

F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A Q  
         C o nfi de ntial   
        A G E N T I D E Cli nical I n vesti gati o nal Pla n , 9 2 2 9 4 6 1 6 , Re v/ Ver G  
Pa ge 6 8  of 9 0  
 
  
T he I C F s hall al wa ys be si g ne d a n d pers o nall y date d b y t he s u bject or le gal re prese ntati ve  
c o m pete nt t o si g n t he I C F u n der t he a p plica ble la ws, r ules, re g ulati o ns a n d g ui deli nes a n d b y 
t he i n vesti gat or a n d/or a n a ut h orize d desi g nee res p o nsi ble f or c o n d ucti n g t he i nf or me d 
c o nse nt pr ocess. If a le gal re prese ntati ve si g ns, t he s u bject s hall be as ke d t o pr o vi de i nf or me d 
c o nse nt f or c o nti n ue d partici pati o n as s o o n as his/ her me dical c o n diti o n all o ws. T he ori gi nal 
si g ne d I C F will be retai ne d b y t he site a n d a c o py of t he si g ne d a n d date d d oc u me nt a n d a n y 
ot her writte n i nf or mati o n m ust be gi ve n t o t he pers o n si g ni n g t he f or m.  
Fail ure t o o btai n s u bject c o nse nt will be re p orte d b y B S C t o t he a p plica ble re g ulat or y 
a ut h orit y  acc or di n g t o t heir re q uire me nts (e. g., F D A re q uire me nt is wit hi n 5 w or ki n g da ys of 
lear ni n g of s uc h a n e ve nt). A n y vi olati o ns of t he i nf or me d c o nse nt pr ocess m ust be re p orte d 
as de viati o ns t o t he s p o ns or a n d l ocal re g ulat or y a ut h orities (e. g. I R B/ E C / R E B), as 
a p pr o priate.  
If ne w i nf or mati o n bec o mes a vaila ble t hat ca n si g nifica ntl y affect a s u bject's f ut ure healt h 
a n d me dical care, t hat i nf or mati o n s hall be pr o vi de d t o t he affecte d s u bject(s) i n writte n f or m 
via a re vise d I C F or, i n s o me sit uati o ns, e nr olle d s u bjects ma y be re q ueste d t o si g n a n d date 
a n a d de n d u m t o t he I C F. I n a d diti o n t o ne w si g nifica nt i nf or mati o n d uri n g t he c o urse of a 
st u d y, ot her sit uati o ns ma y necessitate re visi o n of t he I C F, s uc h as if t here are a me n d me nts 
t o t he a p plica ble la ws, pr ot oc ol, a c ha n ge i n Pri nci pal I n vesti gat or, a d mi nistrati ve c ha n ges, or 
f oll o wi n g a n n ual re vie w b y t he I R B/ E C/ R E B. T he ne w versi o n of t he I C F m ust be a p pr o ve d 
b y t he I R B/ E C / R E B. Acce pta nce  b y B ost o n Scie ntific is re q uire d if c ha n ges t o t he re vise d 
I C F are re q ueste d b y t he site’s I R B/ E C/ R E B. T he I R B/ E C/ R E B will deter mi ne t he s u bject 
p o p ulati o n t o be re -c o nse nte d. 
2 1.  C o m mittees  
 S afety M o nit ori n g Pr ocess  
T o pr o m ote earl y detecti o n of safet y iss ues, B S C pr ocesses will pr o vi de accelerate d 
e val uati o n of safet y e ve nts.  S uccess of t his pr o gra m re q uires d y na mic c ollecti o n of 
u n m o nit ore d data as s o o n as t he e ve nt is re p orte d. T his is e x pe dite d t hr o u g h B S C’s Gl o bal 
Safet y Office, w hic h is res p o nsi ble f or c o or di nati n g t he c ollecti o n of i nf or mati o n f or t he 
s u bject d ossier fr o m t he sites a n d A n gi o gra p hic C ore La b orat or y.  D uri n g re g ularl y 
sc he d ule d m o nit ori n g visits, t he cli nical researc h m o nit ors will s u p p ort t he d y na mic re p orti n g 
pr ocess t hr o u g h t heir re vie w of s o urce d oc u me nt i nf or mati o n .   
 Cli nic al Eve nts  C o m mittee  ( C E C) 
T he Cli nical E ve nts C o m mittee ( C E C) is a n i n de pe n de nt gr o u p of i n di vi d uals wit h perti ne nt 
e x pertise w h o re vie w a n d a dj u dicate i m p orta nt cli nical e n d p oi nts a n d rele va nt A Es re p orte d 
b y st u d y I n vesti gat ors.  
T he C E C will re vie w a safet y e ve nt d ossier, w hic h ma y i ncl u de c o pies of s u bject s o urce 
d oc u me nts pr o vi de d b y st u d y sites, f or all re p orte d cases of ste nt t hr o m b osis, T V R, MI ( Q -
wa ve a n d n o n – Q -wa ve), a n d deat h.  

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C o m mittee me m bers hi p will i ncl u de practiti o ners of car di ol o g y a n d car di o vasc ular 
i nter ve nti o nal t hera p y, as well as ot her e x perts wit h t he necessar y t hera pe utic a n d s u bject 
matter e x pertise t o a dj u dicate t he e ve nt cate g ories o utli ne d a b o ve. Res p o nsi bilitie s, 
q ualificati o ns, me m bers hi p, a n d c o m mittee pr oce d ures are o utli ne d i n t he C E C c harter.  
 Steeri n g C o m mittee  
A Steeri n g C o m mittee c o nsisti n g of S p o ns or Cli nical Ma na ge me nt a n d t he St u d y 
C o or di nati n g PI will be c o n ve ne d.  Res p o nsi bilities ma y i ncl u de o versi g ht of t he o verall 
c o n d uct of t he st u d y w hic h ma y i ncl u de pr ot oc ol de vel o p me nt, st u d y pr o gress, s u bject 
safet y, o verall data q ualit y a n d i nte grit y, a n d ti mel y disse mi nati o n of st u d y res ults t hr o u g h 
a p pr o priate scie n tific sessi o ns a n d p u blicati o ns. As a p pr o priate t he Steeri n g  C o m mittee ma y 
re q uest partici pati o n of A ge nt I D E  I n vesti gat ors o n t he C o m mittee. 
 D at a M o nit ori n g C o m mittee ( D M C)  
T he Data M o nit ori n g C o m mittee ( D M C) is res p o nsi ble f or t he o versi g ht re vie w of all A Es. 
T he D M C will i ncl u de lea di n g e x perts i n car di ol o g y, car di o vasc ular i nter ve nti o nal t hera p y, 
a n d bi ostatistics w h o are n ot partici pati n g i n t he trial a n d w h o ha ve n o affi liati o n wit h B S C. 
D uri n g t he c o urse of t he trial, t he D M C will re vie w acc u m ulati n g safet y data t o m o nit or t he 
i nci de nce of C E C e ve nts a n d ot her tre n ds t hat w o ul d warra nt m o dificati o n or ter mi nati o n of 
t he trial. Res p o nsi bilities, q ualificati o ns, me m bers hi p, a n d c o m mittee pr oce d ures are o utli ne d 
i n t he D M C C harter. 
Data will be s u p plie d t o a n d re vie we d b y t he D M C .  A n y D M C rec o m me n dati o ns f or st u d y 
m o dificati o n or ter mi nati o n beca use of c o ncer ns o ver s u bject safet y or iss ues relati n g t o data 
m o nit ori n g or q ualit y c o ntr ol will be s u b mitte d i n writi n g t o t he E xec uti ve C o m mittee f or 
c o nsi derati o n a n d fi nal decisi o n. H o we ver, if t he D M C at a n y ti me deter mi nes t hat a 
p ote ntiall y seri o us ris k e xists t o s u bjects i n t his trial, t he D M C c hair ma n will i m me diatel y 
n otif y b ot h B S C a n d t he Pri nci pal I n vesti gat or.  
2 2.  S us pe nsi o n or Ter mi n ati o n  
2 2 . 1 Pre m at ure Ter mi n ati o n of t he St u dy  
B ost o n Scie ntific reser ves t he ri g ht t o ter mi nate t he st u d y at a n y sta ge b ut i nte n ds t o e xercise 
t his ri g ht o nl y f or vali d scie ntific or b usi ness  reas o ns a n d reas o ns relate d t o pr otecti o n of 
s u bjects.  I n vesti gat ors, ass ociate d I R Bs/ E Cs/ R E Bs, a n d re g ulat or y a ut h orities, as a p plica ble, 
will be n otifie d i n writi n g i n t he e ve nt of st u d y ter mi nati o n. 
2 2 . 1. 1 Criteri a f or Pre m at ure  Ter mi n ati o n of t he St u d y  
P ossi ble reas o ns f or pre mat ure st u d y ter mi nati o n i ncl u de, b ut are n ot li mite d t o, t he 
f oll o wi n g. 
•  T he occ urre nce of u na ntici pate d a d verse de vice effects t hat prese nt a si g nifica nt or 
u nreas o na ble ris k t o s u bjects e nr olle d i n t he st u d y.  

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•  A n e nr oll me nt rate far bel o w e x pectati o n t hat prej u dices t he c o ncl usi o n of t he st u d y.  
•  A decisi o n o n t he part of B ost o n Scie ntific t o s us pe n d or disc o nti n ue de vel o p me nt of t he 
de vice.  
2 2 . 2 Ter mi n ati o n of St u dy P artici p ati o n by t he I nvesti g at or or Wit h dr a w al of I R B/ E C 
/ R E B A p pr ov al  
A n y i n vesti gat or, or ass ociate d I R B/ E C/ R E B or re g ulat or y a ut h orit y  ma y disc o nti n ue 
partici pati o n i n t he st u d y or wit h dra w a p pr o val of t he st u d y, res pecti vel y, wit h s uita ble 
writte n n otice t o B ost o n Scie ntific.  I n vesti gat ors, ass ociate d I R Bs/ E Cs/ R E Bs, a n d re g ulat or y 
a ut h orities, as a p plica ble, will be n otifie d i n writi n g i n t he e ve nt of t hese occ urre nces. 
2 2 . 3. Re q uire me nts f or D oc u me nt ati o n a n d S u bject F oll o w -u p  
I n t he e ve nt of  pre mat ure st u d y ter mi nati o n, a writte n state me nt as t o w h y t he pre mat ure 
ter mi nati o n has occ urre d will  be pr o vi de d  t o all partici pati n g sites b y B ost o n Scie ntific . T he 
I R B/ E C/ R E B a n d re g ulat or y a ut h orities, as a p plica ble , will  be n otifie d. D etaile d i nf or mati o n 
o n h o w e nr olle d s u bjects will be ma na ge d t hereafter  will be pr o vi de d .  
I n t he e ve nt a n I R B/ E C/R E B  ter mi nates partici pati o n i n t he st u d y, partici pati n g in vesti gat ors, 
ass ociate d I R Bs/ E Cs / R E Bs, a n d re g ulat or y a ut h orities, as a p plica ble, will be n otifie d i n 
writi n g . Detaile d i nf or mati o n o n h o w e nr olle d s u bjects will be ma na ge d t hereafter will be 
pr o vi de d b y B ost o n Scie ntific.  
I n t he e ve nt a Pri nci pal I n vesti gat or ter mi nates partici pati o n i n t he st u d y, st u d y res p o nsi bilit y 
will be tra nsferre d t o a n ot her i n vesti gat or, if p ossi ble. I n t he e ve nt t here are n o o p p ort u nities 
t o tra nsfer Pri nci pal I n vesti gat or res p o nsi bilit y; detaile d i nf or mati o n o n h o w e nr olle d 
s u bjects will be ma na ge d t hereafter will be pr o vi de d b y B ost o n Scie ntific. 
T he Pri nci pal I n vesti gat or or his/ her desi g nee m ust ret ur n all st u d y-relate d d oc u me nts a n d 
i n vesti gati o nal pr o d uct t o B ost o n Scie ntific, u nless t his acti o n w o ul d je o par dize t he ri g hts, 
safet y, or welfare of t he s u bjects. 
2 2 . 4 Criteri a f or S us pe n di n g/ Ter mi n ati n g a St u dy Site  
B ost o n Scie ntific reser ves t he ri g ht t o st o p t he i ncl usi o n of s u bjects at a st u d y site at a n y ti me 
after t he st u d y i nitiati o n visit if n o s u bjects ha ve bee n e nr oll e d, if e nr oll me nt is si g nifica ntl y 
sl o wer t ha n e x pecte d, or if t he site has m ulti ple or  se vere pr ot oc ol vi olati o ns/ n o nco m plia nce 
wit h o ut j ustificati o n a n d/ or fails t o f oll o w re me dial acti o ns.  
I n t he e ve nt of ter mi nati o n of site partici pati o n, all st u d y de vices a n d testi n g e q ui p me nt, as 
a p plica ble, will be ret ur ne d t o B S C  u nless t his acti o n w o ul d je o par dize t he ri g hts, safet y or 
well -bei n g of t he s u bjects. T he  I R B/ E C/ R E B a n d re g ulat or y a ut h orities, as a p plica ble,  will  
be n otifie d . St u d y partici pa nts will be c o ntacte d, as a p plica ble, a n d be i nf or me d of c ha n ges t o 
st u d y visit sc he d ule. 

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2 3.  St u d y Re gistr ati o n a n d Res ults  
 St u dy Re gistr ati o n  
T o c o m pl y wit h a p plica ble la ws a n d re g ulati o ns, t he st u d y will be re gistere d o n a p u blicl y 
accessi ble data base.  
 Cli nic al I nvesti g ati o n Re p ort  
St u d y res ults will be ma de a vaila ble  i n acc or da nce wit h t he le gal re q uire me nts a n d t he 
rec o g nize d et hical pri nci ples, i n acc or da nce wit h t he B ost o n Scie ntific P olic y. A Cli nical 
I n vesti gati o n Re p ort will be ma de a vaila ble t o all i n vesti gat ors, I R B/ E C/ R E B a n d re g ulat or y 
a ut h orities, as a p plica ble i n acc or da nce wit h t he B ost o n Scie ntific P olic y a n d l ocal 
re q uire me nts.  As a p plica ble a n a b bre viate d Cli nical I n vesti gati o n Re p ort will be ma de 
a vaila ble o n a p u blicl y accessi ble data base.  
 P u blic ati o n P olicy  
B S C re q uires discl os ure of its i n v ol ve me nt as a s p o ns or or fi na ncial s u p p orter i n a n y 
p u blicati o n or prese ntati o n relati n g t o a B S C st u d y or its res ults. B S C will s u b mit st u d y 
res ults f or p u blicati o n (re gar dless of st u d y o utc o me) f oll o wi n g t he c o ncl usi o n or ter mi nati o n 
of t he st u d y. B ost o n Scie ntific a d heres t o t he C o ntri b ut ors hi p Criteria set f ort h i n t he 
U nif or m Re q uire me nts of t he I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors (I C MJ E; 
htt p:// w w w.ic mje. or g). I n or der t o e ns ure t he p u blic discl os ure of  st u d y res ults i n a ti mel y 
ma n ner, w hile mai ntai ni n g a n u n biase d prese ntati o n of st u d y o utc o mes, B S C pers o n nel ma y 
assist a ut h ors a n d i n vesti gat ors i n p u blicati o n pre parati o n pr o vi de d t he f oll o wi n g g ui deli nes 
are f oll o we d:  
•  All a ut h ors hi p a n d c o ntri b ut ors hi p re q uire me nts as descri be d a b o ve m ust be f oll o we d.  
•  B S C i n v ol ve me nt i n t he p u blicati o n pre parati o n a n d t he B S C P u blicati o n P olic y s h o ul d 
be disc usse d wit h t he C o or di nati n g Pri nci pal I n vesti gat or(s) a n d/ or E xec uti ve/ Steeri n g 
C o m mittee at t he o nset of t he pr oject.  
•  T he First a n d Se ni or a ut h ors are t he pri mar y dri vers of decisi o ns re gar di n g p u blicati o n 
c o nte nt, re vie w, a p pr o val, a n d s u b missi o n.  
T he data, a nal ytic met h o ds, a n d st u d y materials f or t his cli nical trial ma y  be ma de a vaila ble 
t o ot her researc hers i n acc or da nce wit h t he B ost o n Scie ntific Data S hari n g P olic y 
(htt ps:// w w w. b ost o nscie ntific.c o m/ ).  
2 4.  Bi bli o gr a p h y  
1.   
B yr ne R A, J o ner M, Alf o ns o F, Kastrati A. Dr u g -c oate d ball o o n t hera p y i n c or o nar y 
a n d peri p heral arter y disease. N at ure Revie ws C ar di ol o gy. 2 0 1 3; 1 1( 1): 1 3 -2 3.  

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2.   
Sc heller B, Cre mers B, Sc h mit meier S, Sc h n orr B, Cle ver Y, S pec k U. Dr u g -c oate d 
Ball o o ns –  P ote ntial C or o nar y Vasc ular A p plicati o ns. E ur o pe a n C ar di ol o gy Revie w. 
2 0 1 1; 7( 2): 1 2 2.  
3.   
Kle ber F, Mat he y D, Ritt ger H, Sc heller B. H o w t o use t he dr u g -el uti n g ball o o n: 
rec o m me n dati o ns b y t he Ger ma n c o nse ns us gr o u p. E ur oI nterve nti o n. 
2 0 1 1; 7( K): K 1 2 5 -K 1 2 8.  
4.   
K ol h P, Wij ns W. J oi nt E S C/ E A C T S g ui deli nes o n m y ocar dial re vasc ularizati o n. 
J o ur n al of C ar di ov asc ul ar Me dici ne. 2 0 1 1; 1 2( 4): 2 6 4 -2 6 7.  
5.   
Ha m m C W, D orr O, W oe hrle J, et al. Dr u g -c oate d Ball o o ns f or t he Treat me nt of 
C or o nar y I n -ste nt Reste n osis: A M ultice ntre, Ra n d o mise d C o ntr olle d Cli nical St u d y. 
E ur oI nterve nti o n. 2 0 1 9:[ E p u b a hea d of pri nt].  
6.   
Ha m m C W. Dr u g -c oate d Ball o o ns f or t he Treat me nt of C or o nar y I n -ste nt Reste n osis: 
A Ra n d o mise d, M ultice ntre, C o ntr olle d Cli nical St u d y. E ur o P C R; 2 0 1 7; Paris, 
Fra nce.  
7.   
de We ger V A, Beij ne n J H, Sc helle ns J H M. Cell ular a n d cli nical p har mac ol o g y of t he 
ta xa nes d oceta xel a n d paclita xel –  a re vie w. A nti -C a ncer Dr u gs. 2 0 1 4; 2 5: 4 8 8 -4 9 4.  
8.   
N g V G, Me na C, Pietras C, La ns k y AJ. L ocal deli ver y of paclita xel i n t he treat me nt 
of peri p heral arterial disease. E ur o pe a n J o ur n al of Cli nic al I nvesti g ati o n. 
2 0 1 5; 4 5( 3): 3 3 3 -3 4 5.  
9.   
Ba nerjee S, Sar o de K, M o ha m ma d A, et al. Fe m or o p o pliteal Arter y Ste nt 
T hr o m b osis. Circ ul ati o n: C ar di ov asc ul ar I nterve nti o ns. 2 0 1 6; 9( 2):e 0 0 2 7 3 0.  
1 0.   
Da ke M D, Va n Alsti ne W G, Z h o u Q, Ra g he b A O. P ol y mer -free Paclita xel-c oate d 
Zil ver P T X Ste nts — E val uati o n of P har mac o ki netics a n d C o m parati ve Safet y i n 
P orci ne Arteries. J o ur n al of V asc ul ar a n d I nterve nti o n al R a di ol o gy. 2 0 1 1; 2 2( 5): 6 0 3 -
6 1 0.  
1 1.   
C utli p D E, Wi n dec ker S, Me hra n R, et al. Cli nical e n d p oi nts i n c or o nar y ste nt trials: 
a case f or sta n dar dize d defi niti o ns. Circ ul ati o n. 2 0 0 7; 1 1 5( 1 7): 2 3 4 4 -2 3 5 1.  
 
2 5.  A b bre vi ati o ns a n d Defi niti o ns  
 A b brevi ati o ns  
A b bre viati o ns are s h o w n i n  Ta ble 2 5. 1 -1 .   
T a ble 2 5. 1 -1 : A b bre vi ati o ns 
A b bre vi ati o n/ Acr o n y m   
Ter m  
 
 
A C C  
A merica n C olle ge of Car di ol o g y  
A C T  
acti vate d cl otti n g ti me  
A D E  
a d verse de vice effect  
A E  
a d verse e ve nt  
A H A  
A merica n Heart Ass ociati o n  

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T a ble 2 5. 1 -1 : A b bre vi ati o ns 
A b bre vi ati o n/ Acr o n y m   
Ter m  
A T B C  
A T M  
Acet yl Tri b ut yl Citrate  
at m os p here 
A R C  
Aca de mic Researc h C o ns orti u m  
B S C  
B ost o n Scie ntific C or p orati o n  
B M S  
bare metal ste nt  
C A B G  
c or o nar y arter y b y pass graft  
C B C  
c o m plete bl o o d c o u nt  
C E C  
Cli nical E ve nts C o m mittee  
C K  
creati ne ki nase 
C K -M B  
creati ne ki nase-m y o gl o bi n ba n d, a fracti o n of creati ne ki nase  
C R O  
C o ntract researc h or ga nizati o n  
e C R F 
electr o nic case re p ort f or m  
C V A  
cere br o vasc ular acci de nt  
D E S  
dr u g -el uti n g ste nt 
D F U  
Directi o ns f or Use  
D M C  
Data M o nit ori n g C o m mittee  
E C G  
electr ocar di o gra m  
E D C  
electr o nic data ca pt ure  
E S C  
E ur o pea n S ociet y of Car di ol o g y  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F H U  
First H u ma n Use  
F F R  
fracti o nal fl o w reser ve 
G C P  
G o o d Cli nical Practices  
GI  
gastr oi ntesti nal  
G U S T O  
Gl o bal Strate gies f or O pe ni n g Occl u de d C or o nar y Arteries  
I A B P 
i ntra-a ortic ball o o n p u m p  
I C 
I nterc o nti ne ntal 
I C F 
I nf or me d C o nse nt F or m 
I C H 
I nter nati o nal C o nfere nce o n Har m o nisati o n 
I D E 
I n vesti gati o nal De vice E xe m pti o n 
I E C 
I n de pe n de nt Et hics C o m mittee 
I R B 
I nstit uti o nal Re vie w B oar d 
I S D N 
is os or bi de di nitrate 
I S O 
I nter nati o nal Sta n dar ds Or ga nizati o n 

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T a ble 2 5. 1 -1 : A b bre vi ati o ns 
A b bre vi ati o n/ Acr o n y m   
Ter m  
I S R 
I n ste nt reste n osis  
I T T 
i nte nti o n t o treat 
L A D  
left a nteri or desce n di n g c or o nar y arter y  
L B B B  
left b u n dle bra nc h bl oc k 
L C X  
left circ u mfle x c or o nar y arter y 
M A C E  
maj or a d verse car diac e ve nt  
MI  
m y ocar dial i nfarcti o n  
M L D  
mi ni m u m l u me n dia meter  
N H L BI  
Nati o nal Heart, L u n g, a n d Bl o o d I nstit ute  
N T G  
Nitr o gl yceri n  
O U S  
O utsi de t he U nite d States  
P CI  
perc uta ne o us c or o nar y i nter ve nti o n  
P G  
Perf or ma nce G oal  
P K  
p har mac o ki netics  
P O B A  
Plai n Ol d Ball o o n A n gi o plast y  
P T C A  
Perc uta ne o us tra nsl u mi nal c or o nar y a n gi o plast y  
Q C A  
q ua ntitati ve c or o nar y a n gi o gra p h y  
R C A  
ri g ht c or o nar y arter y 
R V D  
refere nce vessel dia meter 
S A D E  
seri o us a d verse de vice effect 
S A E  
seri o us a d verse e ve nt 
S C AI  
S ociet y f or Car di o vasc ular A n gi o gra p h y a n d I nter ve nti o ns  
S T E MI  
S T ele vati o n m y ocar dial i nfarcti o n  
TI A  
tra nsie nt isc he mic attac k 
TI MI  
T hr o m b ol ysis i n M y ocar dial I nfarcti o n  
T L F  
tar get lesi o n fail ure 
T L R  
tar get lesi o n re vasc ularizati o n 
T V F  
tar get vessel fail ure 
T V R  
tar get vessel re vasc ularizati o n  
U A D E  
u na ntici pate d a d verse de vice effect  
U L N  
u p per li mit of n or mal  
U R L  
u p per refere nce li mit  
U S  
U nite d States  
W B C  
w hite bl o o d cell  

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T a ble 2 5. 1 -1 : A b bre vi ati o ns 
A b bre vi ati o n/ Acr o n y m   
Ter m  
 
 
 
 
 
 
 Defi niti o ns  
Ter ms are defi ne d bel o w.   
 
A B R U P T C L O S U R E  
A br u pt cl os ure is t he occ urre nce of ne w se verel y re d uce d fl o w ( TI MI gra de 0 or 1) wit hi n t he 
tar get vessel t hat persists a n d re q uires bail o ut, i ncl u di n g e mer ge nc y s ur ger y, or res ults i n MI 
or deat h. A br u pt cl os ure re q uires pr o ve n ass ociati o n wit h a mec ha nical dissecti o n of t he 
treat me nt site or i nstr u me nte d vessel, c or o nar y t hr o m b us, or se vere s pas m. A br u pt cl os ure 
d oes n ot c o n n ote “ n o refl o w” d ue t o micr o vasc ular fl o w li mitati o n i n w hic h t he e picar dial 
arter y is pate nt b ut has re d uce d fl o w. A br u pt cl os ure als o d oes n ot c o n n ote tra nsie nt cl os ure 
wit h re d uce d fl o w i n w hic h t he assi g ne d treat me nt re verse d t he cl os ure.  
S u b -a br u pt cl os ure is a n a br u pt cl os ure t hat occ urs after t he tar get pr oce d ure is c o m plete d 
a n d t he s u bject has left t he cat heterizati o n la b orat or y a n d bef ore h os pital disc har ge.  
T hreate ne d a br u pt cl os ure is a gra de  B dissecti o n a n d 5 0 % dia meter ste n osis or a n y 
dissecti o n of gra de  C or hi g her.  
A D V E R S E D E VI C E E F F E C T ( Ref: I S O 1 4 1 5 5 a n d M E D D E V 2. 7/ 3)   
A d verse e ve nt relate d t o t he use of a n i n vesti gati o nal me dical de vice  
N O T E 1: T his i ncl u des a n y a d verse e ve nt res ulti n g fr o m i ns ufficie ncies or 
i na de q uacies i n t he i nstr ucti o ns f or use, t he de pl o y me nt, t he i m pla ntati o n, t he 
i nstallati o n, t he o perati o n, or a n y malf u ncti o n of t he i n vesti gati o nal me dical de vice. 
N O T E 2: T his defi niti o n i ncl u des a n y e ve nt res ulti n g fr o m use err or or i nte nti o nal 
a b n or mal use of t he i n vesti gati o nal me dical de vice.  
A D V E R S E E V E N T ( Ref: I S O 1 4 1 5 5 a n d M E D D E V 2. 7/ 3 ) 
A n y u nt o war d me dical occ urre nce, u ni nte n de d disease or i nj ur y, or a n y u nt o war d cli nical 
si g ns (i ncl u di n g a n a b n or mal la b orat or y fi n di n g) i n s u bjects, users or ot her pers o ns, w het her 
or n ot relate d t o t he i n vesti gati o nal me dical de vice.  
N O T E 1: T his i ncl u des e ve nts relate d t o t he i n vesti gati o nal me dical de vice or c o m parat or.  
N O T E 2: T his defi niti o n i ncl u des e ve nts relate d t o t he pr oce d ures i n v ol ve d.  
N O T E 3: F or users or ot her pers o ns, t his defi niti o n is restricte d t o e ve nts relate d t o t he 
i n vesti gati o nal me dical de vice. 
A D V E R S E E V E N T R E L A TI O N S HI P T E R M S  

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A d verse E ve nt Relati o ns hi p ter ms are detaile d i n secti o n 2 0. 3 -1.   
A N GI O G R A P HI C S U C C E S S  
A n gi o gra p hic s uccess is a mea n lesi o n dia meter ste n osis < 5 0 % ( < 3 0 % f or ste nts) i n 2 near -
ort h o g o nal pr ojecti o ns wit h TI MI 3fl o w, as vis uall y assesse d b y t he p h ysicia n, wit h o ut t he 
occ urre nce of pr ol o n ge d c hest pai n or E C G c ha n ges c o nsiste nt wit h MI  
A N N U A L F O L L O W -U P S  
A n n ual f oll o w -u ps are t h ose t hat occ ur a n n uall y t hr o u g h 2  years after t he i n de x pr oce d ure. 
T he ti mi n g of a n n ual f oll o w -u ps is calc ulate d base d o n o ne cale n dar year e q uali n g 3 6 5  da ys. 
T he f oll o w -u p wi n d o w is 3 0  da ys. T heref ore, t he 1 -year a n d 2 -year f oll o w -u ps s h o ul d occ ur 
3 6 5 3 0  da ys a n d 7 3 0 3 0  da ys after t he i n de x pr oce d ure, res pecti vel y.  
A N TI CI P A T E D E V E N T  
E ve nt t hat is pre vi o usl y i de ntifie d i n t he Pr ot oc ol, I C F, or D F U.  
A R R H Y T H MI A  
A n arr h yt h mia is a n y variati o n fr o m t he n or mal r h yt h m of t he heart, i ncl u di n g si n us 
arr h yt h mia, pre mat ure beats, heart bl oc k, atrial or ve ntric ular fi brillati o n, atrial or ve ntric ular 
fl utter, a n d atrial or ve ntric ular tac h ycar dia. 
A R T E RI O V E N O U S FI S T U L A  
A n arteri o ve n o us fist ula is a n a b n or mal passa ge or c o m m u nicati o n bet wee n a n arter y a n d a 
vei n. It ma y res ult fr o m i nj ur y or it ma y occ ur as a c o n ge nital a b n or malit y.  
B AI L O U T  
•  Bail o ut t y picall y refers t o a persiste nt  dissecti o n b ut ca n als o i ncl u de a vessel 
c o m plicati o n at t he osti u m or al o n g t he c o urse of t he maj or c or o nar y arter y use d t o 
access t he tar get lesi o n.  
•  T he decisi o n of w het her t o treat i n a bail o ut sit uati o n is at t he discreti o n of t he 
i nter ve nti o nalist. 
BI F U R C A TI O N L E SI O N  
A bif urcati o n lesi o n is a lesi o n ass ociate d wit h t he area w here a bra nc h vessel > 2. 0  m m i n 
dia meter b y vis ual esti mate ori gi nates.  
BI N A R Y R E S T E N O SI S  
Bi nar y reste n osis is a dia meter ste n osis > 5 0 % at t he pre vi o usl y treate d lesi o n site, i ncl u di n g 
t he ori gi nall y treate d area a n d t he a djace nt pr o xi mal a n d distal Q C A a nal ysis se g me nt. 
B L E E DI N G C L A S SI FI C A TI O N S ( Ref: G U S T O ) 
•  Se vere or life -t hreate ni n g: Eit her i ntracra nial he m orr ha ge or blee di n g t hat ca uses 
he m o d y na mic c o m pr o mise a n d re q uires i nter ve nti o n  
•  M o derate: Blee di n g t hat re q uires bl o o d tra nsf usi o n b ut d oes n ot res ult i n he m o d y na mic 
c o m pr o mise  

F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A Q  
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•  Mil d: Blee di n g t hat d oes n ot meet criteria f or eit her se vere or m o derate blee di n g  
 
B R A U N W A L D C L A S SI FI C A TI O N O F U N S T A B L E A N GI N A  
Se verit y  
•  Class  I: Ne w o nset, se vere or accelerate d a n gi na. S u bjects wit h a n gi na of less t ha n 
2  m o nt hs d urati o n, se vere or occ urri n g 3 or m ore ti mes per da y, or a n gi na t hat is 
disti nctl y m ore fre q ue nt a n d preci pitate d b y disti nctl y less e xerti o n; n o pai n at rest i n t he 
last 2 m o nt hs.  
•  Class  II: A n gi na at rest, s u bac ute.  S u bjects wit h 1 or m ore e pis o des of a n gi na at rest 
d uri n g t he prece di n g m o nt h, b ut n ot wit hi n t he prece di n g 4 8  h o urs.  
•  Class  III: A n gi na at rest, ac ute. S u bjects wit h 1 or m ore e pis o des of a n gi na at rest wit hi n 
t he prece di n g 4 8 h o urs.  
Cli nical Circ u msta nces  
•  Class  A: Sec o n dar y u nsta ble a n gi na. A clearl y i de ntifie d c o n diti o n e xtri nsic t o t he 
c or o nar y vasc ular be d t hat has i nte nsifie d m y ocar dial isc he mia (e. g., a ne mia, fe ver, 
i nfecti o n, h y p ote nsi o n, tac h yarr h yt h mia, t h yr ot o xic osis, a n d h y p o xe mia sec o n dar y t o 
respirat or y fail ure).  
•  Class  B: Pri mar y u nsta ble a n gi na.  
•  Class  C: P osti nfarcti o n u nsta ble a n gi na ( wit hi n 2  wee ks of d oc u me nte d MI).  
 
C A N A DI A N C A R DI O V A S C U L A R S O CI E T Y C L A S SI FI C A TI O N  
•  Class  1: Or di nar y p h ysical acti vit y d oes n ot ca use a n gi na, s uc h as wal ki n g a n d cli m bi n g 
stairs. A n gi na wit h stre n u o us or ra pi d or pr ol o n ge d e xerti o n at w or k or recreati o n. 
•  Class  2: Sli g ht li mitati o n of or di nar y acti vit y. Wal ki n g or cli m bi n g stairs ra pi dl y, wal ki n g 
u p hill, wal ki n g or stair cli m bi n g after meals, or i n c ol d, or i n wi n d, or u n der e m oti o nal 
stress, or a n y o nl y d uri n g t he first h o urs after a wa ke ni n g. Wal ki n g m ore t ha n 2 bl oc ks o n 
t he le vel a n d cli m bi n g m ore t ha n 1 fli g ht of or di nar y stairs at a n or mal pace a n d i n 
n or mal c o n diti o ns.  
•  Class  3: Mar ke d li mitati o ns of or di nar y p h ysical acti vit y. Wal ki n g 1 t o 2 bl oc ks o n t he 
le vel a n d cli m bi n g 1 fli g ht of stairs i n n or mal c o n diti o ns a n d at a n or mal pace. 
•  Class  4: I na bilit y t o carr y o n a n y p h ysical acti vit y wit h o ut disc o mf ort; a n gi na s y n dr o me 
ma y be prese nt  at rest. 
 
C A R DI A C T A M P O N A D E  
Car diac ta m p o na de is a n ac ute c o m pressi o n of t he heart d ue t o eff usi o n of t he fl ui d i nt o t he 
pericar di u m, or t he c ollecti o n of bl o o d i n t he pericar di u m, fr o m r u pt ure of t he heart or 
pe netrati n g tra u ma.  
C A R DI O G E NI C S H O C K  
Car di o ge nic s h oc k is a cli nical state of h y p o perf usi o n c haracterize d b y a s yst olic bl o o d 
press ure < 8 0  m m H g a n d/ or a ce ntral filli n g press ure > 2 0  m m H g, or a car diac i n de x 

F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A Q  
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< 1. 8  liters/ mi n/ m2 w here t here is e vi de nce of i ns ufficie nt e n d or ga n pr of usi o n. S h oc k is als o 
c o nsi dere d prese nt if i ntra ve n o us i n otr o pes a n d/ or i ntra -a ortic ball o o n p u m p (I A B P) are 
nee de d t o mai ntai n a s yst olic bl o o d press ure > 8 0  m m H g a n d a car diac i n de x 
> 1. 8  liters/ mi n ute/ m2. 
C R E A TI N E KI N A S E -M Y O G L O BI N B A N D  
Creati ne ki nase -m y o gl o bi n ba n d ( C K -M B) is a n is oe nz y me of creati ne ki nase ( C K) wit h a 
disti nct m olec ular str uct ure s pecific as a n i n dicat or of m y ocar dial cell i nj ur y. It is use d t o 
e val uate p ossi ble ca uses of c hest pai n, t o detect a n d dia g n ose ac ute MI a n d  re-i nfarcti o n, a n d 
t o m o nit or t he se verit y of m y ocar dial isc he mia. 
C LI NI C A L E V E N T S C O M MI T T E E  
A C E C is a n i n de pe n de nt gr o u p of i n di vi d uals wit h perti ne nt e x pertise t hat re vie w a n d 
a dj u dicate i m p orta nt e n d p oi nts a n d rele va nt A Es re p orte d b y st u d y i n vesti gat ors.  
C LI NI C A L E V E N T S C O M MI T T E E E V E N T  
T he C E C will a dj u dicate all re p orte d cases of ste nt t hr o m b osis, T V R, MI ( Q -wa ve a n d n o n –
Q -wa ve), a n d deat h (t o e ns ure a p pr o priate classificati o n of deat h as car diac or n o n -car diac). 
A case a dj u dicate d b y t he C E C is c o nsi dere d t o be a C E C e ve nt.  
C LI NI C A L P R O C E D U R A L S U C C E S S  
Cli nical pr oce d ural s uccess is p ost pr oce d ure dia meter ste n osis < 3 0 % i n 2 near -ort h o g o nal 
pr ojecti o ns wit h TI MI 3 fl o w i n t he tar get lesi o n, as vis uall y assesse d b y t he p h ysicia n, 
wit h o ut t he occ urre nce of i n -h os pital MI, T V R, or car diac deat h.  
C O M P LI C A TI O N ( A N GI O G R A P HI C O R C LI NI C A L)  
A c o m plicati o n (a n gi o gra p hic or cli nical) is a n u n desira ble cli nical e ve nt t hat res ults i n deat h, 
i nj ur y, or i n vasi ve i nter ve nti o n. C o m plicati o ns ma y i ncl u de, b ut are n ot li mite d t o, 
perf orati o n, occl usi o n, i nti mal fla p, dissecti o n, l oss of si de bra nc h, di stal e m b olizati o n, n o n-
fatal MI, ele vate d C K T otal, pr ol o n ge d a n gi na, h y p ote nsi o n, he mat o ma, arr h yt h mias, etc. 
C o m plicati o ns ma y or ma y n ot be relate d t o t he i n vesti gati o nal de vice.  
C O N G E S TI V E H E A R T F AI L U R E  
C o n gesti ve heart fail ure is a n i na de q uac y of t he heart s uc h t hat it fails t o mai ntai n a de q uate 
circ ulati o n of bl o o d, s o t hat c o n gesti o n a n d e de ma de vel o p i n t he tiss ues. Cli nical s y n dr o me 
is c haracterize d b y s h ort ness of breat h, n o n-pitti n g e de ma, e nlar ge m e nt of t he li ver, e n g or ge d 
nec k vei ns, a n d p ul m o nar y rales.  
C O R O N A R Y A N E U R Y S M  
A c or o nar y a ne ur ys m is a pat h ol o gic dilati o n of a se g me nt of a bl o o d vessel i n v ol vi n g all 
t hree la yers of t he vessel wall 1. 5 × t he R V D.  
C O R O N A R Y A R T E R Y S P A S M  
C or o nar y arter y s pas m, or c or o nar y vas os pas m, is a s pas m of a c or o nar y arter y, res ulti n g i n a 
decrease i n l u me n dia meter. It ma y occ ur distal t o t he treat me nt site a n d is ge nerall y re verse d 
wit h i ntrac or o nar y a d mi nistrati o n of N T G or wit h a dj u nct ball o o n dilati o n.  

F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A Q  
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D E A T H  
Deat h is cate g orize d as car diac or n o n -car diac. 
Car diac deat h  is defi ne d as deat h d ue t o a n y of t he f oll o wi n g. 
•  Ac ute MI  
•  Car diac perf orati o n/ pericar dial ta m p o na de  
•  Arr h yt h mia or c o n d ucti o n a b n or malit y  
•  C V A t hr o u g h h os pital disc har ge or C V A s us pecte d of bei n g relate d t o t he pr oce d ure  
•  Deat h d ue t o c o m plicati o n of t he pr oce d ure, i ncl u di n g blee di n g, vasc ular re pair, 
tra nsf usi o n reacti o n, or b y pass s ur ger y 
•  A n y deat h i n w hic h a car diac ca use ca n n ot be e xcl u de d  
N o n -car diac deat h  is defi ne d as a deat h n ot d ue t o car diac ca uses as defi ne d a b o ve. 
D E VI C E D E FI CI E N C Y ( Ref: I S O 1 4 1 5 5 a n d M E D D E V 2. 7/ 3 ) 
A i na de q uac y of a n i n vesti gati o nal me dical de vice relate d t o its i de ntit y, q ualit y, d ura bilit y, 
relia bilit y, safet y or perf or ma nce. T his ma y i ncl u de malf u ncti o ns, use err or, or i na de q uac y i n 
t he i nf or mati o n s u p plie d b y t he ma n ufact urer. 
DI S S E C TI O N, N H L BI C L A S SI FI C A TI O N  
•  T y pe  A: S mall ra di ol uce nt area wit hi n t he l u me n of t he vessel disa p peari n g wit h t he 
passa ge of t he c o ntrast material  
•  T y pe  B: A p peara nce of c o ntrast me di u m parallel t o t he l u me n of t he vessel disa p peari n g 
wit hi n a fe w car diac c ycles  
•  T y pe  C: Dissecti o n pr otr u di n g o utsi de t he l u me n of t he vessel persisti n g after passa ge of 
t he c o ntrast material 
•  T y pe  D: S piral s ha pe d filli n g defect wit h or wit h o ut dela ye d r u n -off of t he c o ntrast 
material i n t he a nte gra de fl o w  
•  T y pe  E: Persiste nt l u mi nal filli n g defect wit h dela ye d r u n -off of t he c o ntrast material i n 
t he distal l u me n 
•  T y pe  F: Filli n g defect acc o m pa nie d b y t otal c or o nar y occl usi o n  
 
DI A B E T E S M E L LI T U S  
S u bjects will be cate g orize d as ha vi n g dia betes mellit us if me dical treat me nt ( oral or 
i njecti o n) is re q uire d f or c o ntr ol of bl o o d gl uc ose le vels. 
DI S T A L E M B O LI Z A TI O N  
Distal e m b olizati o n is mi grati o n of a filli n g defect or t hr o m b us t o distall y occl u de t he tar get 
vessel or o ne of its bra nc hes.  
E M E R G E N C Y B Y P A S S S U R G E R Y  
E mer ge nc y b y pass s ur ger y is C A B G s ur ger y perf or me d o n a n ur ge nt or e mer ge nt basis f or 
se vere vessel dissecti o n or cl os ure, or treat me nt fail ure res ulti n g i n ne w isc he mia. 
E PI C A R DI A L V E S S E L  

F or m/ Te m plate 9 0 7 0 2 6 3 7 _ Re v/ Ver A Q  
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E picar dial vessels i ncl u de t he L A D a n d its bra nc hes, t he L C X a n d its bra nc hes, a n d t he R C A 
a n d its bra nc hes.  
E Q -5 D T M  
A sta n dar dize d i nstr u me nt de vel o pe d b y t he E ur o Q ol Gr o u p as a meas ure of healt h -relate d 
q ualit y of life. T he descri pti ve s yste m of healt h -relate d q ualit y of life states c o nsist of fi ve 
di me nsi o ns ( m o bilit y, self -care, us ual acti vities, pai n/ disc o mf ort, a n xiet y/ de pressi o n) eac h of 
w hic h ca n ta ke o ne of fi ve res p o nses. T he res p o nses rec or d fi ve le vels of se veri t y ( n o 
pr o ble ms/sli g ht pr o ble ms/ m o derate pr o ble ms/se vere pr o ble ms/e xtre me pr o ble ms) wit hi n a 
partic ular E Q -5 D di me nsi o n  
H Y P E R T E N SI O N  
H y perte nsi o n is persiste ntl y hi g h arterial bl o o d press ure. Vari o us criteria f or its t hres h ol d 
ha ve bee n s u g geste d, ra n gi n g fr o m 1 4 0  m m H g s yst olic a n d 9 0  m m H g diast olic t o as hi g h as 
2 2 0  m m H g s yst olic a n d 1 1 0  m m H g diast olic. H y perte nsi o n ma y ha ve n o k n o w n c a use or be 
ass ociate d wit h ot her pri mar y diseases.  
H Y P O T E N SI O N  
S ustai ne d h y p ote nsi o n is a s yst olic bl o o d press ure less t ha n 8 0  m m H g lasti n g m ore t ha n 
3 0  mi n utes or re q uiri n g i nter ve nti o n (e. g., paci n g, I A B P, i ntra ve n o us vas o press ors, t o s ustai n 
s yst olic bl o o d press ure). T his e xcl u des tra nsie nt h y p ote nsi o n or va gal reacti o ns, w hic h are 
self-li mite d or rea dil y re versi ble. 
I N D E X P R O C E D U R E S T A R T TI M E 
I n de x pr oce d ure start ti me is defi ne d as t he ti me of s heat h i nserti o n. If a pre vi o usl y place d 
s heat h is use d (i.e., fr o m a n earlier dia g n ostic pr oce d ure), i n de x pr oce d ure start ti me is 
defi ne d as t he ti me of g ui de cat heter i nserti o n i nt o s heat h f or t he i nt er ve nti o nal pr oce d ure.  
I N D E X P R O C E D U R E E N D TI M E 
I n de x pr oce d ure e n d ti me is defi ne d as t he ti me t he g ui de cat heter is re m o ve d after t he fi nal 
a n gi o gra p h y.  
I N TI M A L F L A P 
 A n e xtr usi o n of tiss ue e xte n di n g fr o m t he arterial s urface i nt o t he l u me n ( 0 = a bse nt; 1 = 
prese nt) .  
 
L E F T M AI N DI S E A S E  
Left mai n disease is a si g nifica nt lesi o n i n t he left mai n c or o nar y arter y of at least 5 0 % 
dia meter ste n osis. A pr otecte d left mai n arter y mea ns t he vessels s u p plie d b y t he disease d left 
mai n  ( us uall y t he L A D a n d C X) are s u p plie d b y a f u ncti o ni n g graft, eit her ve n o us or arterial, 
c o n necte d  t o a n y of t he bra nc hes of t he left c or o nar y arter y . A  ste nt i n t he left mai n c or o nar y 
arter y d oes n ot i n itself c o nstit ute a pr otecte d left mai n.  
L E SI O N C H A R A C T E RI S TI C S ( A C C/ A H A C L A S SI FI C A TI O N)  

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•  T y pe  A lesi o ns: Mi ni mall y c o m ple x, le n gt h < 1 0  m m, c o nce ntric, rea dil y accessi ble, 
n o n -a n g ulate d se g me nt ( < 4 5 ), s m o ot h c o nt o ur, little or n o calcificati o n, less t ha n t otall y 
occl usi ve, n ot ostial i n l ocati o n, n o maj or si de bra nc h i n v ol ve me nt, a n d a n a bse nce of 
t hr o m b us. 
•  T y pe  B lesi o ns: M o deratel y c o m ple x, t u b ular (le n gt h 1 0 t o 2 0  m m), ecce ntric, m o derate 
t ort u osit y of pr o xi mal se g me nt, m o deratel y a n g ulate d se g me nt ( > 4 5, < 9 0), irre g ular 
c o nt o ur, m o derate or hea v y calcificati o n, t otal occl usi o ns < 3  m o nt hs ol d, ostial i n 
l ocati o n, bif urcati o n lesi o ns re q uiri n g d o u ble g ui de wire, a n d s o me t hr o m b us prese nt. 
•  T y pe  C lesi o ns: Se verel y c o m ple x, diff use (le n gt h 2 0  m m), e xcessi ve t ort u osit y of 
pr o xi mal se g me nt, e xtre mel y a n g ulate d se g me nts > 9 0 , t otal occl usi o ns > 3 m o nt hs ol d 
a n d/ or bri d gi n g c ollaterals, i na bilit y t o pr otect maj or si de bra nc hes, a n d de ge nerate d vei n 
grafts wit h fria ble lesi o ns.  
 
L E SI O N L E N G T H  
Lesi o n le n gt h is meas ure d as dista nce fr o m t he pr o xi mal t o t he distal s h o ul der i n t he vie w 
t hat de m o nstrates t he ste n osis i n its m ost el o n gate d pr ojecti o n. Lesi o n le n gt h is classifie d as 
discrete ( < 1 0  m m), t u b ular ( 1 0 -2 0  m m), or diff use ( > 2 0  m m).  
L E SI O N L O C A TI O N  
Lesi o n l ocati o n is t he l ocati o n of t he lesi o n acc or di n g t o t he s pecific c or o nar y arter y (i.e., left 
mai n, L A D, L C X, or R C A) or b y pass graft, a n d is s pecifie d as pr o xi mal, mi d, or distal. A 
sta n dar d ma p will be pr o vi de d t o be use d f or l ocati o n descri pti o ns. 
N ote:  I n t he A ge nt I D E trial, t he ra m us will be c o nsi dere d t o be a bra nc h of t he L C X f or 
p ur p oses of deter mi ni n g eli gi bilit y a n d f or deter mi ni n g T V R.  
L E U K O P E NI A  
Le u k o pe nia is a le u k oc yte c o u nt of < 3. 0  ×  1 0 9/liter f or m ore t ha n 3 da ys.  
M A L F U N C TI O N  
A malf u ncti o n is a fail ure of t he de vice t o meet perf or ma nce s pecificati o ns or ot her wise 
perf or m as i nte n de d.  
M U L TI -V E S S E L DI S E A S E  
M ulti -vessel disease refers t o t he prese nce of > 5 0 % dia meter ste n osis as meas ure d b y cali per 
met h o d or Q C A o n -li ne i n 2 or 3 maj or e picar dial c or o nar y vessels or b y passe d bra nc hes. 
M Y O C A R DI A L I N F A R C TI O N  
I n t he A G E N T I D E trial, MI will be a dj u dicate d  acc or di n g t o t he S C AI , 4t h U ni versal a n d 
A R C -2  M y ocar dial I nfarcti o n defi niti o n s.  MI e n d p oi nt e ve nts will be a nal yze d base d  o n t he 
S C AI defi niti o n f or peri-pr oce d ural MI a n d 4 t h U ni versal defi niti o n f or s p o nta ne o us MI.  
( 1) S C AI MI Defi niti o n:  
I n p atie nts wit h n or m al b aseli ne C K-M B : 

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T he pea k C K -M B meas ure d wit hi n 4 8 h o urs of t he pr oce d ure rises t o _ 1 0 x t he l ocal 
la b orat or y U L N, or t o _ 5 x U L N wit h ne w pat h ol o gic Q-wa ves i n _ 2 c o nti g u o us lea ds or ne w 
persiste nt L B B B, O R i n t he a bse nce of C K -M B meas ure me nts a n d a n or mal baseli ne c T n, a 
cT n (I or T) le vel meas ure d wit hi n 4 8 h o urs of t he P CI rises t o _ 7 0 x t he l ocal la b orat or y  
U L N, or _ 3 5 x U L N wit h ne w pat h ol o gic Q -wa ves i n _ 2 c o nti g u o us lea ds or ne w persiste nt 
L B B B.  
 
I n patie nts wit h ele vate d baseli ne C K-M B ( or c T n) i n w h o m t he bi o mar ker le vels are sta ble 
or falli n g:  
 
T he C K -M B ( or c T n) rises b y a n a bs ol ute i ncre me nt e q ual t o t h ose le vels rec o m me n de d 
a b o ve fr o m t he m ost rece nt pre -pr oce d ure le vel.  
 
I n patie nts wit h ele vate d C K-M B ( or c T n) i n w h o m t he bi o mar ker le vels ha ve n ot bee n 
s h o w n t o be sta ble or falli n g: 
 
T he C K -M B ( or c T n) rises b y a n a bs ol ute i ncre me nt e q ual t o t h ose le vels rec o m me n de d 
a b o ve pl us ne w S T -se g me nt ele vati o n or de pressi o n pl us si g ns c o nsiste nt wit h a cli nicall y 
rele va nt MI, s uc h as ne w o nset or w orse ni n g heart fail ure or s ustai ne d h y p ote nsi o n. 
( 2) T he 4 t h U ni versal MI Defi niti o n :  
Ac ute MI (ty pes 1, 2 a n d 3 MI) : 
T he ter m ac ute m y ocar dial i nfarcti o n s h o ul d be use d w he n t here is ac ute m y ocar dial i nj ur y 
wit h cli nical e vi de nce of ac ute m y ocar dial isc he mia a n d wit h detecti o n of a rise a n d/ or fall of 
car diac tr o p o ni n (c T n) val ues wit h at least o ne val ue a b o ve t he 9 9t h perce ntile u p per 
refere nce li mit ( U R L) A N D  at least o ne of t he f oll o wi n g:  
•  S y m pt o ms of m y ocar dial isc he mia  
•  Ne w isc he mic E C G c ha n ges  
•  De vel o p me nt of pat h ol o gical Q wa ves  
•  I ma gi n g e vi de nce of ne w l oss of via ble m y ocar di u m or ne w re gi o nal wall m oti o n 
a b n or malit y i n a patter n c o nsiste nt wit h a n isc he mic eti ol o g y  
•  I de ntificati o n of a c or o nar y t hr o m b us b y a n gi o gra p h y or a ut o ps y ( n ot f or t y pes 2 or 3 
MIs)  
P ost -m orte m de m o nstr ati o n of ac ute at her o -t hr o m b osis i n t he artery s u p plyi n g t he i nf arcte d 
my oc ar di u m meets criteri a f or ty pe 1 MI.  
Evi de nce of a n i m b al a nce bet wee n my oc ar di al oxy ge n s u p ply a n d de m a n d u nrel ate d t o ac ute 
at her o -t hr o m b osis meets criteri a f or ty pe 2 MI. 
My oc ar di al I nf arcti o n res ulti n g i n de at h w he n bi o m arker v al ues are u n av ail a ble (ty pe 3 MI):  

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Car diac deat h wit h s y m pt o ms s u g gesti ve of m y ocar dial isc he mia a n d pres u me d ne w 
isc he mic E C G c ha n ges bef ore c T n val ues bec o me a vaila ble or a b n or mal, b ut deat h occ urre d 
bef ore car diac bi o mar kers were o btai ne d, or bef ore car diac bi o mar kers c o ul d be i de ntifie d , or 
MI was detecte d b y a n a ut o ps y e xa mi nati o n.  
Perc ut a ne o us C or o n ary I nterve nti o n -Rel ate d My oc ar di al I nf arcti o n (ty pe 4 a MI) a n d 
C or o n ary Artery By p ass Gr afti n g -Rel ate d My oc ar di al I nf arcti o n (ty pe 5 MI):  
Perc uta ne o us c or o nar y i nter ve nti o n ( P CI) relate d MI ≤4 8 h o urs after t he i n de x pr oce d ure is 
ar bitraril y defi ne d b y a n ele vati o n of c T n val ues > 5 ti mes f or t y pe 4a MI a n d > 1 0 ti mes f or 
t y pe 5 MI of t he 9 9t h perce ntile U R L i n patie nts wit h n or mal baseli ne val ues. Patie nts wit h 
ele vate d pre pr oce d ural c T n val ues, i n w h o m t he pre pr oce d ural c T n le vel are sta ble ( ≤2 0 % 
variati o n) or falli n g, m ust meet t he criteria f or a > 5 - or > 1 0 -f ol d i ncrease a n d ma nifest a 
c ha n ge fr o m t he baseli ne val ue of > 2 0 %.  
A N D  
O ne of t he f oll o wi n g:  
•  Ne w isc he mic E C G c ha n ges (t his criteri o n is relate d t o t y pe 4a MI o nl y)  
•  De vel o p me nt of ne w pat h ol o gical Q wa ves  
•  A n gi o gra p hic fi n di n gs c o nsiste nt wit h a pr oce d ural fl o w -li miti n g c o m plicati o n s uc h 
as c or o nar y dissecti o n, occl usi o n of a maj or e picar dial arter y or graft, si de -bra nc h 
occl usi o n -t hr o m b us, disr u pti o n of c ollateral fl o w or distal e m b olizati o n 
•  I ma gi n g e vi de nce of l oss of via ble m y ocar di u m t hat is pres u me d t o be ne w a n d, i n a 
patter n c o nsiste nt wit h a n isc he mic eti ol o g y  
Is ol ate d devel o p me nt of ne w p at h ol o gic al Q w aves meets t he ty pe 4 a MI or ty pe 5 MI criteri a 
wit h eit her rev asc ul ariz ati o n pr oce d ure if c T n v al ues are  elev ate d a n d risi n g b ut less t h a n 
t he pre -s pecifie d t hres h ol ds f or P CI a n d C A B G. 
Ot her ty pes of 4 MI i ncl u de ty pe 4 b MI ste nt t hr o m b osis a n d ty pe 4c MI reste n osis  t h at b ot h 
meet ty pe 1 MI criteri a.  
P ost -m orte m de m o nstr ati o n of a pr oce d ure -rel ate d t hr o m b us meets t he ty pe 4 a MI criteri a or 
ty pe 4 b MI criteri a if ass oci ate d wit h a ste nt. 
Criteri a f or pri or or sile nt/ u nrec o g nize d my oc ar di al i nf arcti o n : 
A n y o ne of t he f oll o wi n g criteria meets t he dia g n osis f or pri or or sile nt/ u nrec o g nize d MI:  
•  A b n or mal Q wa ves wit h or wit h o ut s y m pt o ms i n t he a bse nce of n o n -isc he mic ca uses 
•  I ma gi n g e vi de nce of l oss of via ble m y ocar di u m i n a patter n c o nsiste nt wit h isc he mic 
eti ol o g y 
•  Pat h o -a nat o mical fi n di n gs of a pri or MI  

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( 3) A R C -2  MI Defi niti o n  
S p o nt a ne o us  MI : 
A R C -2 e n d orses t he classificati o n of s p o nta ne o us MI  a n d MI relate d t o c o m plicati o ns of t he  
st u d y de vice (t y pes 1, 2, 3, 4 b, a n d 4c) pr o p ose d b y t he 2 0 1 2 u ni versal defi niti o n of MI.  
S us pecte d s p o nta ne o us MI tri g gers, f or w hic h a bi o mar ker rise is d oc u me nte d wit h o ut clear  
e vi de nce of a t y pe 1 or 2 MI, s h o ul d  be a dj u dicate d a n d re p orte d as “ m y ocar dial i nj ur y n ot  
meeti n g MI criteria”  
Peri pr oce d ur al My oc ar di al I nf arcti o n Perc ut a ne o us C or o n ary I nterve nti o n a n d C or o n ary 
Artery By p ass Gr afti n g ( Wit hi n 4 8 H o urs)  
A bs ol ute rise i n car diac tr o p o ni n (fr o m baseli ne) ≥3 5 ti mes t he 9 9t h perce ntile U R L  
A N D  
O ne or m ore of t he f oll o wi n g : 
•  Ne w si g nifica nt Q wa ves or e q ui vale nt  
•  Fl o w -li miti n g a n gi o gra p hic c o m plicati o ns 
•  Ne w “s u bsta ntial” l oss of m y ocar di u m o n i ma gi n g  
N O N -T A R G E T L E SI O N  
A n o n -tar get lesi o n is a n y lesi o n treate d d uri n g t he i n de x pr oce d ure w hic h is n ot a tar get 
lesi o n. A ma xi m u m of 1 n o n -tar get lesi o n i n 1 n o n -tar get vessel ma y be treate d wit h a 
c o m mercial treat me nt (e. g., ste nt, ball o o n a n gi o plast y, e xcl u di n g brac h yt hera p y ) d uri n g t he 
i n de x pr oce d ure.  
P E R F O R A TI O N  
Perf orati o ns are classifie d as f oll o ws:  
•  A n gi o gra p hic perf orati o n: Perf orati o n detecte d b y cli nical site or A n gi o gra p hic C ore 
La b orat or y at a n y p oi nt d uri n g t he pr oce d ure.  
•  Cli nical perf orati o n: Perf orati o n re q uiri n g a d diti o nal treat me nt, i ncl u di n g eff orts t o seal 
t he perf orati o n or pericar dial drai na ge, or res ulti n g i n si g nifica nt pericar dial eff usi o n, 
a br u pt cl os ure, MI, or deat h.  
•  Pericar dial he m orr ha ge/ta m p o na de: Perf orati o n ca usi n g ta m p o na de.  
 
P O B A  
Mec ha nical ball o o n e x pa nsi o n of a c or o nar y ste n osis wit h o ut ste nt i m pla ntati o n or dr u g 
deli ver y  
P R O L O N G E D A N GI N A P E C T O RI S  
Pr ol o n ge d a n gi na pect oris is a n gi na lasti n g l o n ger t ha n 1  h o ur.  
P S E U D O A N E U R Y S M  

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A pse u d oa ne ur ys m is a n e nca ps ulate d he mat o ma i n c o m m u nicati o n wit h a n arter y. It is ofte n 
diffic ult t o disti n g uis h fr o m a n e x pa n di n g he mat o ma at t he site of arterial p u nct ure.  
R E F E R E N C E V E S S E L DI A M E T E R ( R V D)  
Refere nce dia meter of t he n or mal arter y se g me nt is a n a n gi o gra p hic meas ure me nt of t he 
arter y pr o xi mal a n d/ or distal t o t he lesi o n i nte n de d f or i nter ve nti o n. T his is als o referre d t o as 
“refere nce vessel dia meter” ( R V D).  
R E P E A T I N T E R V E N TI O N  
Re peat i nter ve nti o n is a P CI or C A B G perf or me d after t he  i n de x pr oce d ure e n ds T he  re peat 
i nter ve nti o n s h o ul d be perf or me d t o i m pr o ve bl o o d fl o w. 
R E S T E N O S E D L E SI O N  
A reste n ose d lesi o n is a pre vi o usl y treate d lesi o n t hat a gai n has a ste n osis.  
R E S T E N O SI S  
See Bi nar y Reste n osis.  
S E RI O U S A D V E R S E D E VI C E E F F E C T ( Ref: I S O 1 4 1 5 5 a n d M E D D E V 2. 7/ 3 ) 
A d verse de vice effect t hat has res ulte d i n a n y of t he c o nse q ue nces c haracteristic of a seri o us 
a d verse e ve nt.  
S E RI O U S A D V E R S E E V E N T ( Ref: I S O 1 4 1 5 5 a n d M E D D E V 2. 7/ 3 ) 
A d verse e ve nt t hat:  
a) Le d t o deat h,  
•  b) Le d t o  seri o us deteri orati o n i n t he healt h of t he s u bject as defi ne d b y  eit her: 
1)  a life-t hreate ni n g ill ness or i nj ur y, or 
2)  a per ma ne nt i m pair me nt of a b o d y str uct ure or a b o d y f u ncti o n, or  
3)  i n-patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n , or  
4)  me dical or s ur gical i nter ve nti o n t o pre ve nt life -t hreate ni n g ill ness or i nj ur y or 
per ma ne nt i m pair me nt t o a b o d y str uct ure or a b o d y f u ncti o n  
•  
c) Le d t o fetal distress, fetal deat h, or a c o n ge nital a b n or malit y or birt h defect.  
N O T E 1: Pla n ne d h os pitalizati o n f or a pre -e xisti n g c o n diti o n, or a pr oce d ure re q uire d b y t he 
cli nical i n vesti gati o nal pla n, wit h o ut a seri o us deteri orati o n i n healt h, is n ot c o nsi dere d a 
seri o us a d verse e ve nt.  
 
S O U R C E D A T A   
All i nf or mati o n i n ori gi nal rec or ds a n d certifie d c o pies of ori gi nal rec or ds of cli nical 
fi n di n gs, o bser vati o ns, or ot her acti vities i n a cli nical trial necessar y f or t he rec o nstr ucti o n 
a n d e val uati o n of t he trial. S o urce data are c o ntai ne d i n t he s o urce d oc u me nts ( ori gi nal 
rec or ds or certifie d c o pies) (I C H E 6 ( 1. 5 1 a n d 1. 5 2))   
S O U R C E D O C U M E N T S  

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Ori gi nal d oc u me nts, data, a n d rec or ds  (I C H E 6 ( 1. 5 1 a n d 1. 5 2))   
S T E N T T H R O M B O SI S ( Ref: Ac a de mic Rese arc h C o ns orti u m Defi niti o n ) 1 1 
Ste nt t hr o m b osis is t he ac ute occl usi o n or ste n osis of a n i ntra vasc ular ste nt ca use d b y i n sit u 
t hr o m b osis. Ste nt t hr o m b osis s h o ul d be re p orte d as a c u m ulati ve val ue at t he differe nt ti me 
p oi nts a n d wit h t he differe nt se parate ti me p oi nts. Ti me 0 is defi ne d as t he ti me p oi nt after 
t he g ui de cat heter has bee n re m o ve d a n d t he patie nt left t he cat heterizati o n la b. 
Ti mi n g:  
•  Ac ute ste nt t hr o m b osis *: 0 -2 4  h o urs after ste nt i m pla ntati o n  
•  S u bac ute ste nt t hr o m b osis *: > 2 4  h o urs t o 3 0  da ys after ste nt i m pla ntati o n  
•  Late ste nt t hr o m b osis: > 3 0  da ys t o 1  year after ste nt i m pla ntati o n  
•  Ver y late ste nt t hr o m b osis: > 1  year after ste nt i m pla ntati o n  
* Ac ute/s u bac ute ca n als o be re place d b y earl y ste nt t hr o m b osis. Earl y ste nt t hr o m b osis is 
0 -3 0  da ys.  
Ste nt t hr o m b osis ma y be defi ne d as:  
•  C o nfir me d/ defi nite  
•  Pr o ba ble  
•  P ossi ble  
C o nfir me d/ Defi nite  (is c o nsi dere d eit her a n gi o gra p hic c o nfir me d or pat h ol o gic c o nfir me d)  
A n gi o gra p hic c o nfir me d ste nt t hr o m b osis is c o nsi dere d t o ha ve occ urre d if:  
•  TI MI fl o w is:  
TI MI fl o w gra de 0 wit h occl usi o n ori gi nati n g i n t he ste nt or i n t he se g me nt 5  m m pr o xi mal 
or distal t o t he ste nt re gi o n i n t he prese nce of t hr o m b us *  
TI MI fl o w gra de 1, 2 or 3 ori gi nati n g i n t he ste nt or i n t he se g me nt 5  m m pr o xi mal or distal 
t o t he ste nt re gi o n i n t he prese nce of a t hr o m b us * 
A N D  at least o ne of t he f oll o wi n g criteria, u p t o 4 8  h o urs, has bee n f ulfille d:  
•  Ne w o nset of isc he mic s y m pt o ms at rest (t y pical c hest pai n wit h d urati o n > 2 0  mi n utes)  
•  Ne w isc he mic E C G c ha n ges s u g gesti ve of ac ute isc he mia  
•  T y pical rise a n d fall i n car diac bi o mar kers ( > 2 ×  U L N of C K)  
 
T he i nci de ntal a n gi o gra p hic d oc u me ntati o n of ste nt occl usi o n i n t he a bse nce of cli nical 
s y n dr o mes is n ot c o nsi dere d a c o nfir me d ste nt t hr o m b osis (sile nt t hr o m b osis). 
* I ntrac or o nar y t hr o m b us  
N o n -occl usive t hr o m b us : S p heroi d , o v oi d or irre g ular n o n-calcifie d filli n g defect or l uce nc y 
s urr o u n de d b y c o ntrast material ( o n 3 si des of wit hi n a c or o nar y ste n osis) see n i n m ulti ple 
pr ojecti o ns, or persiste nce of c o ntrast material wit hi n t he l u me n, or a visi ble e m b olizati o n of 
i ntral umi nal material d o w nstrea m.  

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Occl usive t hr o m b us:  A TI MI 0 or TI MI 1 i ntra -ste nt or pr o xi mal t o a ste nt u p t o t he m ost 
a djace nt pr o xi mal si de bra nc h or mai n bra nc h (if ori gi nati n g fr o m t he si de bra nc h).  
Pr o ba ble  
Cli nical defi niti o n of pr o ba ble ste nt t hr o m b osis is c o nsi dere d t o ha ve occ urre d i n t he 
f oll o wi n g cases: 
•  A n y u ne x plai ne d deat h wit hi n t he first 3 0  da ys  
•  Irres pecti ve of t he ti me after t he i n de x pr oce d ure a n d MI i n t he a bse nce of a n y o b vi o us 
ca use w hic h is relate d t o d oc u me nte d ac ute isc he mia i n t he territ or y of t he i m pla nte d 
ste nt wit h o ut a n gi o gra p hic c o nfir mati o n of ste nt t hr o m b osis 
 
P ossi ble  
Cli nical defi niti o n of p ossi ble ste nt t hr o m b osis is c o nsi dere d t o ha ve occ urre d wit h a n y 
u ne x plai ne d deat h be y o n d 3 0  da ys.  
S T R O K E/ C E R E B R O V A S C U L A R A C CI D E N T  
A n ac ute s y m pt o matic e pis o de of ne ur ol o gical d ysf u ncti o n attri b ute d t o a vasc ular ca use 
lasti n g m ore t ha n 2 4 h o urs or lasti n g 2 4 h o urs or less wit h a brai n i ma gi n g st u d y or a ut o ps y 
s h o wi n g i nfarcti o n. 
Classificati o n:  
•  Isc he mic Str o ke: A n ac ute s y m pt o matic e pis o de of f ocal cere bral, s pi nal, or reti nal 
d ysf u ncti o n ca use d b y a n i nfarcti o n of ce ntral ner v o us s yste m tiss ue.  
•  He m orr ha gic Str o ke: A n ac ute s y m pt o matic e pis o de of f ocal or gl o bal cere bral or s pi nal 
d ysf u ncti o n ca use d b y a n o ntra u matic i ntra pare nc h y mal, i ntra ve ntric ular, or s u barac h n oi d 
he m orr ha ge.  
•  U n deter mi ne d Str o ke: A str o ke wit h i ns ufficie nt i nf or mati o n t o all o w cate g orizati o n as 
isc he mic or he m orr ha gic. 
A n e ve nt t hat lasts < 2 4 h o urs ma y be a dj u dicate d as a str o ke if t he f oll o wi n g treat me nts 
were use d:  
•  P har mac ol o gic, i. e., t hr o m b ol ytic dr u g a d mi nistrati o n, or  
•  N o n -p har mac ol o gic, i.e., ne ur oi nter ve nti o nal pr oce d ure ( e. g., i ntracra nial a n gi o plast y) 
 
S U C C E S S F U L P R E DI L A TI O N/ P R E T R E A T M E N T  
S uccessf ul pre dilati o n/ pretreat me nt refers t o dilati o n wit h a ball o o n cat heter of a p pr o priate 
le n gt h a n d dia meter, or pretreat me nt wit h directi o nal or r otati o nal c or o nar y at herect o m y, 
laser or c utti n g/sc ori n g ball o o n wit h n o greater t ha n 5 0 % resi d ual ste n osis a n d n o dissecti o n 
greater t ha n N H L BI t y pe  C.  
T A R G E T L E SI O N  
T he tar get lesi o n is t he lesi o n selecte d b y t he I n vesti gat or f or treat me nt wit h a st u d y de vice .  
T he tar get lesi o n a nal ysis se g me nt i ncl u des t he arterial se g me nt treate d wit h t he st u d y ste nt 

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pl us t he arterial se g me nt 5 m m pr o xi mal a n d 5 m m distal t o t he treat me nt site. T he tar get 
lesi o n s h o ul d meet t he a n gi o gra p hic selecti o n criteria.  
T A R G E T L E SI O N F AI L U R E  
Tar get lesi o n fail ure is a n y isc he mia -dri ve n re vasc ularizati o n of t he tar get lesi o n, MI ( Q -
wa ve a n d n o n – Q -wa ve) relate d t o t he tar get vessel, or (car diac) deat h. F or t he p ur p oses of 
t his pr ot oc ol, if it ca n n ot be deter mi ne d wit h certai nt y w het her t he MI was relate d t o t he 
tar get vessel, it will be c o nsi dere d a T L F. 
T A R G E T L E SI O N R E V A S C U L A RI Z A TI O N  
Tar get lesi o n re vasc ularizati o n is a n y isc he mia -dri ve n re peat perc uta ne o us i nter ve nti o n, t o 
i m pr o ve bl o o d fl o w, of t he s uccessf ull y treate d tar get lesi o n or b y pass s ur ger y of t he tar get 
vessel wit h a graft distall y t o t he s uccessf ull y treate d tar get lesi o n . A T L R will be c o nsi dere d 
isc he mia-dri ve n if t he tar get lesi o n dia meter ste n osis is 5 0 % b y Q C A a n d t here is prese nce 
of cli nical or f u ncti o nal isc he mia w hic h ca n n ot be e x plai ne d b y ot her c or o nar y or graft 
lesi o ns. Cli nical or f u ncti o nal isc he mia is a n y of t he f oll o wi n g: 
•  T he s u bject has a p ositi ve f u ncti o nal st u d y c orres p o n di n g t o t he area ser ve d b y t he tar get 
lesi o n. 
•  T he s u bject has isc he mic E C G c ha n ges at rest i n a distri b uti o n c o nsiste nt wit h t he tar get 
vessel.  
•  T he s u bject has isc he mic s y m pt o ms refera ble t o t he tar get lesi o n. 
A T L R will be c o nsi dere d as isc he mia -dri ve n if t he lesi o n dia meter ste n osis is 7 0 % b y 
Q C A e ve n i n t he a bse nce of cli nical or f u ncti o nal isc he mia. 
T A R G E T V E S S E L  
T he tar get vessel is a n y c or o nar y vessel (e. g., left mai n c or o nar y arter y, L A D, L C X, or R C A) 
c o ntai ni n g a tar get lesi o n. Si de bra nc hes of a tar get vessel s uc h as t he L A D are als o 
c o nsi dere d part of t he tar get vessel.  
T A R G E T V E S S E L F AI L U R E  
Tar get vessel fail ure is a n y isc he mia -dri ve n re vasc ularizati o n of t he tar get vessel, MI ( Q -
wa ve a n d n o n – Q -wa ve) relate d t o t he tar get vessel or car diac deat h. F or t he p ur p oses of t his 
pr ot oc ol, if it ca n n ot be deter mi ne d wit h certai nt y w het her t he MI or deat h was relate d t o t he 
tar get vessel, it will be c o nsi dere d a T V F. 
T A R G E T V E S S E L R E V A S C U L A RI Z A TI O N  
Tar get vessel re vasc ularizati o n is defi ne d as a T L R (see defi niti o n a b o ve) or a T V R re m ote 
(see defi niti o n bel o w). 
T A R G E T V E S S E L R E V A S C U L A RI Z A TI O N R E M O T E  
Tar get vessel re vasc ularizati o n re m ote is a n y isc he mia -dri ve n re peat perc uta ne o us 
i nter ve nti o n, t o i m pr o ve bl o o d fl o w, or b y pass s ur ger y of n ot pre vi o usl y e xisti n g lesi o ns 
dia meter ste n osis ≥5 0 % b y Q C A i n t he tar get vessel, e xcl u di n g t he tar get lesi o n. A T V R will 
be c o nsi dere d isc he mia -dri ve n if t he tar get vessel dia meter ste n osis is 5 0 % b y Q C A a n d a n y 
of t he f oll o wi n g are prese nt:  

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•  T he s u bject has a p ositi ve f u ncti o nal st u d y c orres p o n di n g t o t he area ser ve d b y t he tar get 
vessel.  
•  T he s u bject has isc he mic E C G c ha n ges at rest i n a distri b uti o n c o nsiste nt wit h t he tar get 
vessel.  
•  T he s u bject has isc he mic s y m pt o ms refera ble t o t he tar get vessel.  
A T V R will als o be c o nsi dere d as isc he mia -dri ve n if t he lesi o n dia meter ste n osis is 7 0 % 
e ve n i n t he a bse nce of cli nical or f u ncti o nal isc he mia.  
T E C H NI C A L S U C C E S S  
Tec h nical s uccess is s uccessf ul cr ossi n g a n d dilati o n of t he lesi o n, wit h o ut ball o o n r u pt ure, 
a n d p ost -pr oce d ure dia meter ste n osis of < 3 0 % i n 2 near -ort h o g o nal pr ojecti o ns wit h TI MI 3 
fl o w i n t he tar get lesi o n, as vis uall y assesse d b y t he p h ysicia n.  
T E C H NI CI A N W O R K S H E E T  
A Tec h nicia n W or ks heet is a rec or d f or listi n g t he fil mi n g se q ue nce a n d a n g ulati o ns of x -ra y 
e q ui p me nt, details of i nflati o ns, a n d descri pti o n of lesi o n(s).  
T H R O M B U S ( A N GI O G R A P HI C)  
T hr o m b us (a n gi o gra p hic) is discrete, m o bile i ntral u mi nal filli n g wit h defi ne d b or ders 
wit h/ wit h o ut ass ociate d c o ntrast strai ni n g, classifie d as eit her a bse nt or prese nt.  
T H R O M B O L Y SI S I N M Y O C A R DI A L I N F A R C TI O N C L A S SI FI C A TI O N  
•  TI MI  0: N o a nter o gra de fl o w be y o n d t he p oi nt of occl usi o n . 
•  TI MI  1: C o ntrast passes t he p oi nt of o bstr ucti o n b ut ha n gs u p a n d fails t o o pacif y t he 
e ntire distal c or o nar y be d d uri n g t he d urati o n of t he a n gi o gra p hic fil mi n g se q ue nce . 
•  TI MI  2: C o ntrast o pacifies t he e ntire c or o nar y be d distal t o t he ste n osis b ut t he rate of 
e ntr y a n d/ or cleara nce is sl o wer t ha n i n t he c o m para ble areas n ot perf use d b y t he dilate d 
vessel.  S pecificall y, a nter o gra de filli n g of c o ntrast wit h c o m plete filli n g of t he arter y a n d 
its maj or a n d mi n or bra nc hes after m ore t ha n 3 f ull car diac c ycles.  Alter nati vel y, dela ye d 
c o ntrast was h o ut i n t he tar get lesi o n territ or y ma y occ ur, c o m pare d wit h c o m para ble 
areas of m y ocar di u m n ot perf use d b y t he tar get lesi o n . 
•  TI MI  3: C o m plete perf usi o n. S pecificall y,  a nter o gra de fl o w of c o ntrast wit h c o m plete 
filli n g of t he arter y a n d its maj or a n d mi n or bra nc hes wit hi n 3 f ull car diac c ycles.  
C o ntrast als o clears fr o m t he arterial se g me nt wit hi n 3 f ull car diac c ycles . 
T O T A L O C C L U SI O N  
A t otal occl usi o n is a lesi o n wit h n o fl o w (i.e., TI MI fl o w  0).  A t otal occl usi o n is c o nsi dere d 
c hr o nic if t he vessel has bee n cl ose d f or > 3 m o nt hs.  
T R A N SI E N T I S C H E MI C A T T A C K  
A TI A is a f ocal isc he mic ne ur ol o gical deficit of a br u pt o nset a n d of pres u me d vasc ular 
eti ol o g y t hat res ol ves c o m pletel y wit hi n 2 4  h o urs of o nset.  
U N A N TI CI P A T E D A D V E R S E D E VI C E E F F E C T ( Ref: 2 1 C F R P art 8 1 2 ) 
A n y seri o us a d verse effect o n healt h or safet y or a n y life -t hreate ni n g pr o ble m or deat h 
ca use d b y, or ass ociate d wit h a de vice, if t hat effect, pr o ble m, or deat h was n ot pre vi o usl y 

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i de ntifie d i n nat ure, se verit y, or de gree of i nci de nce i n t he pr ot oc ol or a p plicati o n (i ncl u di n g 
a s u p ple me ntar y pla n or a p plicati o n), or a n y ot her u na ntici pate d seri o us pr o ble m ass ociate d 
wit h a de vice t hat relates t o t he ri g hts, safet y, or welfare of s u b jects. 
U N A N TI CI P A T E D S E RI O U S A D V E R S E D E VI C E E F F E C T ( Ref: I S O 1 4 1 5 5 a n d 
M E D D E V 2. 7/ 3 ) 
Seri o us a d verse de vice effect w hic h b y its nat ure, i nci de nce, se verit y, or o utc o me has n ot 
bee n i de ntifie d i n t he c urre nt versi o n of t he ris k a nal ysis re p ort.  
N O T E 1 : A ntici pate d seri o us a d verse de vice effect ( A S A D E) is a n effect w hic h b y its 
nat ure, i nci de nce, se verit y or o utc o me has bee n i de ntifie d i n t he ris k a nal ysis re p ort.