Conditions: Severe Clostridium Difficile Infection Severe-Complicated/Fulminant Clostridium Difficile Infection
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 15
Healthy volunteers: no

Brief summary:
This is a randomized, open label, comparative, Phase II study to determine whether fecal microbiota transplant using Penn Microbiome Therapy products helps standard therapy to treat severe Clostridium difficile infection (C diff).

Detailed description:

Arms:
arm 1: Participants who receive the antibiotics usually prescribed for C diff infection. arm 2: Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor arm 3: Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery).

Interventions: intervention 1: Penn Microbiome Therapy - 001 intervention 2: Penn Microbiome Therapy - 002 intervention 3: Penn Microbiome Therapy - 003 intervention 4: Antibiotics
Intervention descriptions: intervention 1: Fecal Microbiota for Transplant, enema product intervention 2: Fecal Microbiota for Transplant, suspension product intervention 3: Fecal Microbiota for Transplant, capsule product intervention 4: Standard of care antibiotics

Protocol document:
Prot_SAP_000.pdf: 


 
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T a ble of C o nte nts 
 
 
LI S T O F A B B R E VI A TI O N S  ......................................................................................................................... 5 
S T U D Y S U M M A R Y  ...................................................................................................................................... 6 
B A C K G R O U N D A N D S T U D Y  R A TI O N A L E  ............................................................................................... 9 
1.  
I N T R O D U C TI O N ................................................................................................................................. 9 
1. 1.  B A C K G R O U N D A N D R E L E V A N T L I T E R A T U R E .......................................................................................... 9 
1. 2.  N A M E A N D D E S C RI P TI O N O F T H E IN V E S TI G A TI O N A L P R O D U C T  ............................................................... 1 0  
1. 2. 1.  
N o n -Cli nic al D at a  ............................................................................................................... 1 0  
1. 2. 2.  
Cli nic al D at a t o D ate  ........................................................................................................... 1 1  
1. 3.  D O S E R A TI O N A L E .............................................................................................................................. 1 3  
2.  
S T U D Y O B J E C TI V E S  ........................................................................................................................ 1 3  
2. 1.  P RI M A R Y O BJ E C TI V E  ......................................................................................................................... 1 3  
2. 2.  S E C O N D A R Y O BJ E C TI V E  ..................................................................................................................... 1 3  
2. 3.  E X P L O R A T O R Y O BJ E C TI V E  ................................................................................................................. 1 3  
3.  
I N V E S TI G A TI O N A L P L A N .............................................................................................................. 1 3  
3. 1.  G E N E R A L D E SI G N  ............................................................................................................................. 1 3  
3. 1. 1.  
Scree ni n g P h ase  .................................................................................................................. 1 4  
3. 1. 2.  
St u dy I nterve nti o n P h ase  ...................................................................................................... 1 4  
3. 1. 3.  
P ost -P M T A d mi nistr ati o n m o nit ori n g: Be dsi de f or 6 0 Mi n utes  ................................................ 1 4  
3. 1. 4.  
P ost -P M T A d mi nistr ati o n m o nit ori n g: D aily f or 3 D ays after A d mi nistr ati o n/ E nr oll me nt  .......... 1 5  
3. 1. 5.  
P ost -P M T A d mi nistr ati o n F oll o w -U p  .................................................................................... 1 5  
3. 1. 6.  
All oc ati o n t o I nterve nt i o n al Gr o u p ........................................................................................ 1 6  
3. 2.  S T U D Y E N D P OI N T S  ............................................................................................................................ 1 8  
3. 2. 1.  
Pri m ary St u dy E n d p oi nts  ...................................................................................................... 1 8  
3. 2. 2.  
Sec o n d ary St u dy E n d p oi nts  .................................................................................................. 1 8  
3. 2. 3.  
Pri m ary S afety E n d p oi nts  ..................................................................................................... 1 8  
4.  
S T U D Y P O P U L A TI O N A N D  D U R A TI O N O F P A R TI CI P A TI O N  ..................................................... 1 9  
4. 1.  IN C L U SI O N C RI T E RI A  ......................................................................................................................... 1 9  
4. 2.  E X C L U SI O N C RI T E RI A  ........................................................................................................................ 2 0  
4. 3.  S U BJ E C T R E C R UI T M E N T  ..................................................................................................................... 2 1  
4. 4.  D U R A TI O N O F S T U D Y P A R TI CI P A TI O N .................................................................................................. 2 1  
4. 5.  T O T A L N U M B E R O F S U BJ E C T S A N D S I T E S............................................................................................. 2 1  
4. 6.  V U L N E R A B L E P O P U L A TI O N S  ............................................................................................................... 2 1  
5.  
S T U D Y I N T E R V E N TI O N  .................................................................................................................. 2 2  
5. 1.  D E S C RI P TI O N  .................................................................................................................................... 2 2  
5. 2.  IN T E R V E N TI O N R E GI M E N  ................................................................................................................... 2 2  
5. 3.  R E C EI P T  ........................................................................................................................................... 2 2  
5. 4.  S T O R A G E  .......................................................................................................................................... 2 3  
5. 5.  P R E P A R A TI O N A N D P A C K A GI N G  .......................................................................................................... 2 3  
5. 6.  B LI N DI N G  ......................................................................................................................................... 2 3  
5. 7.  A D MI NI S T R A TI O N A N D A C C O U N T A BI LI T Y  ............................................................................................ 2 3  
5. 8.  S U BJ E C T C O M P LI A N C E M O NI T O RI N G  ................................................................................................... 2 4  
5. 9.  R E T U R N O R D E S T R U C TI O N O F IN V E S TI G A TI O N A L P R O D U C T  ................................................................... 2 4  
6.  
S T U D Y P R O C E D U R E S  ...................................................................................................................... 2 4  
6. 1.  S C R E E NI N G A N D E N R O L L M E N T  ........................................................................................................... 2 4  


 
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6. 1. 1.  
S urveill a nce Test Revie w  ...................................................................................................... 2 4  
6. 1. 2.  
Me dic al Rec or d Revie w f or I ncl usi o n/ Excl usi o n Criteri a  ........................................................ 2 4  
6. 1. 3.  
I nf or me d C o nse nt ................................................................................................................ 2 4  
6. 1. 4.  
E nter al Access C heck  ........................................................................................................... 2 5  
6. 1. 5.  
R a n d o miz ati o n  .................................................................................................................... 2 5  
6. 2.  S T U D Y IN T E R V E N TI O N P H A S E  ............................................................................................................. 2 5  
6. 2. 1.  
P M T Pr o d uct Recei pt  ........................................................................................................... 2 5 
6. 2. 2.  
A d mi nistr ati o n  ..................................................................................................................... 2 5  
6. 2. 3.  
P ost -I nterve nti o n 6 0 mi n utes ................................................................................................ 2 5  
6. 2. 4.  
P ost -I nterve nti o n 3 D ays ...................................................................................................... 2 6  
6. 3.  S T U D Y F O L L O W -U P P H A S E  ................................................................................................................. 2 6  
6. 3. 1.  
F oll o w -u p 7 d ays  ................................................................................................................. 2 6  
6. 3. 2.  
F ol l o w-u p 3 0 d ays  ............................................................................................................... 2 7  
6. 3. 3.  
F oll o w -u p 9 0 d ays  ............................................................................................................... 2 7  
6. 3. 4.  
E n d -of -st u dy visit at 1 8 0 d ays ............................................................................................... 2 7  
6. 4.  R E S C U E T H E R A P Y  ............................................................................................................................. 2 7  
6. 5.  U N S C H E D U L E D V I SI T S ....................................................................................................................... 2 7  
6. 6.  S U BJ E C T W
I T H D R A W A L ..................................................................................................................... 2 8  
6. 6. 1.  
D at a C ollecti o n  ................................................................................................................... 2 8  
6. 7.  E A R L Y T E R MI N A TI O N V I SI T S .............................................................................................................. 2 8  
7.  
S T U D Y E V A L U A TI O N S A N D  M E A S U R E M E N T S  ........................................................................... 3 0  
7. 1.  M E DI C A L R E C O R D R E VI E W  ................................................................................................................ 3 0  
7. 2.  P H Y SI C A L E X A MI N A TI O N  ................................................................................................................... 3 0  
7. 3.  V I T A L S I G N S ..................................................................................................................................... 3 0  
7. 4.  L A B O R A T O R Y E V A L U A TI O N S .............................................................................................................. 3 0  
7. 5.  P R E G N A N C Y T E S TI N G  ........................................................................................................................ 3 0  
7. 6.  O T H E R  E V A L U A TI O N S , M E A S U R E S  ...................................................................................................... 3 0  
7. 7.  E F FI C A C Y E V A L U A TI O N S  ................................................................................................................... 3 0  
7. 8.  G E N E TI C T E S TI N G (O N L Y I F A P P LI C A B L E ) ............................................................................................ 3 1  
7. 9.  S A F E T Y E V A L U A TI O N S  ...................................................................................................................... 3 1  
7. 9. 1.  
Dev i ati o ns a n d Exce pti o ns.................................................................................................... 3 1  
7. 9. 2.  
S afety P ar a meters  ................................................................................................................ 3 1  
8.  
S T A TI S TI C A L P L A N  ......................................................................................................................... 3 2  
8. 1.  P RI M A R Y E N D P OI N T  .......................................................................................................................... 3 2  
8. 2.  S E C O N D A R Y E N D P OI N T S  .................................................................................................................... 3 2  
8. 3.  E X P L O R A T O R Y E N D P OI N T S  ................................................................................................................ 3 2  
8. 4.  S A M P L E S I Z E A N D P O W E R D E T E R MI N A TI O N  ......................................................................................... 3 2  
8. 5.  S T A TI S TI C A L M E T H O D S  ..................................................................................................................... 3 3  
8. 5. 1.  
B aseli ne D at a  ...................................................................................................................... 3 3  
8. 5. 2.  
Effic acy A n alysis  ................................................................................................................. 3 4  
8. 5. 3.  
I nteri m A n alysis .................................................................................................................. 3 4  
8. 5. 4.  
S afety A n alysis  .................................................................................................................... 3 4  
8. 5. 5.  
Ex pl or at ory A n alyses  ........................................................................................................... 3 4  
8. 6.  S U BJ E C T P O P U L A TI O N (S ) F O R A N A L Y SI S  ............................................................................................. 3 4  
9.  
S A F E T Y A N D A D V E R S E E V E N T S  ................................................................................................... 3 4  
9. 1.  D E FI NI TI O N S  ..................................................................................................................................... 3 4  
9. 1. 1.  
A dverse Eve nt ...................................................................................................................... 3 4  
9. 1. 2.  
Seri o us A dverse Eve nt  .......................................................................................................... 3 5  
9. 1. 3.  
A dverse Eve nts of S peci al I nterest ( A E SI)  .............................................................................. 3 5  
9. 1. 4.  
Ex pecte d A dverse Eve nts  ...................................................................................................... 3 6  
9. 2.  R E C O R DI N G O F A D V E R S E E V E N T S  ....................................................................................................... 3 6  
9. 3.  R E P O R TI N G O F A D V E R S E E V E N T S A N D U N A N TI CI P A T E D P R O B L E M S  ....................................................... 3 7  


 
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9. 3. 1.  
Pre g n a ncy  ........................................................................................................................... 3 8  
9. 4.  T O XI CI T Y M A N A G E M E N T , S T O P PI N G R U L E S A N D S T U D Y T E R MI N A TI O N  .................................................. 3 8  
9. 5.  M E DI C A L M O NI T O RI N G  ..................................................................................................................... 3 8  
9. 5. 1.  
D at a a n d S afety M o nit ori n g Pl a n  .......................................................................................... 3 8  
9. 5. 2.  
D at a S afety M o nit ori n g B o ar d  .............................................................................................. 3 8  
1 0.  
S T U D Y A D MI NI S T R A TI O N , D A T A H A N D LI N G A N D R E C O R D K E E PI N G .................................. 3 9  
1 0. 1.  C O N FI D E N TI A LI T Y  ............................................................................................................................. 3 9  
1 0. 2.  F U T U R E U S E O F S T O R E D S P E CI M E N S A N D D A T A  ................................................................................... 3 9  
1 0. 3.  D A T A C O L L E C TI O N A N D M A N A G E M E N T  .............................................................................................. 3 9  
1 0. 4.  R E C O R D S R E T E N TI O N  ........................................................................................................................ 3 9  
1 1.  
S T U D Y M O NI T O RI N G, A U DI TI N G, A N D I N S P E C TI N G  ................................................................ 4 0  
1 1. 1.  S T U D Y M O NI T O RI N G P L A N  ................................................................................................................. 4 0  
1 1. 2.  D A T A Q U A LI T Y A S S U R A N C E  .............................................................................................................. 4 0  
1 1. 3.  A U DI TI N G A N D IN S P E C TI N G  ................................................................................................................ 4 0  
1 2.  
E T HI C A L C O N SI D E R A TI O N S  ......................................................................................................... 4 0  
1 2. 1.  R I S K S ............................................................................................................................................... 4 1  
1 2. 2.  B E N E FI T S  ......................................................................................................................................... 4 1  
1 2. 3.  R I S K B E N E FI T A S S E S S M E N T  ............................................................................................................... 4 1  
1 2. 4.  IN F O R M E D C O N S E N T P R O C E S S / HI P A A  A U T H O RI Z A TI O N  ..................................................................... 4 1  
1 3.  
S T U D Y FI N A N C E S  ............................................................................................................................ 4 2  
1 3. 1.  F U N DI N G S O U R C E  ............................................................................................................................. 4 2  
1 3. 2.  C O N F LI C T O F IN T E R E S T  ...................................................................................................................... 4 2  
1 3. 3.  S U BJ E C T S TI P E N D S O R P A Y M E N T S  ....................................................................................................... 4 2  
1 4.  
P U B LI C A TI O N P L A N  ....................................................................................................................... 4 2  
1 5.  
R E F E R E N C E S  ................................................................................................................................... 4 2  
 
T a ble of T a bles  
 
T a ble 1: F M T d osi n g a n d ass ociate d ris ks  ........................................................................................................ 1 2  
T a ble 2: E nr oll me nt a n d stratificati o n criteria  ................................................................................................... 2 0  
T a ble 3: Sc he d ule of st u d y pr oce d ures  ............................................................................................................. 2 9  
 
 


 
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List of A b bre vi ati o ns  
 
A E:  A d verse e ve nt  
A E SI : A d verse e ve nt of s pecial i nterest 
A F T : acceler ate d f ail ure ti me  
A N C:  A bs ol ute ne utr o p hil c o u nt 
B MI:  b o d y m ass i n de x 
C C H:  C hester C o u nt y H os pital 
C DI:  Cl ostri di u m difficile  i nfecti o n 
C F R:  C o de of fe deral r e g ulati o ns 
C F U: c ol o n y- f or mi n g u nits 
C R C:  cli nical researc h c o or di nat or  
D S M B:  Data safet y m o nit ori n g b oar d 
EI A:  e nz y me i m m u n oassa y 
F M T:  Fecal Micr o bi ota Tra ns pla ntati o n  
g : gra ms  
HI P A A:  Healt h I ns ura nce P orta bilit y  a n d A cc o u nta bilit y Act of 1 9 9 6 
H U P:  H os pital of t he U ni versit y of Pe n ns yl va ni a 
I C H: I nter nati o nal C o nf ere nce o n Har m o nisati o n 
I D S A: I nfecti o us Diseas es S ociet y of A merica 
I T T: i nte nti o n t o treat 
L G H:  La ncaster G e neral H os pital  
m L : milliliters  
m- I T T: m o difie d i nte nti o n t o treat 
P A H:  Pe n ns yl v a nia H os pital 
P HI:  pr ot ecte d h ealt h i nf or mati o n ( P HI) 
P M P M C:  Pe n n Me dici ne Pri ncet o n Me dical Ce nter ( P M P M C) 
P M T:  Pe n n Micr o bi o me T hera p y 
P PI:  pr ot o n p u m p i n hi bit or 
P P M C:  Pe n n-Pr es b yt eri a n Me dical Ce nter  
R- C DI:  Rec urr e nt Cl ostri di u m difficile  i nfecti o n 
S A E : Seri o us A d verse E ve nt 
S/ S C/ F -C DI:  se v ere or s e vere-c o m plicate d/f ul mi na nt Cl ostri di u m difficile  i nfecti o n 
SI R S:  s yste mic i nfla m m at or y res p o nse s y n dr o me 
S U S A R:  S us pecte d u ne x pecte d seri o us a d vers e reacti o n  
W B C : w hite bl o o d cells 


 
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St u d y  S u m m ar y  
Title  
A P hase II, Ra n d o mize d Trial t o E val uate t he Safet y a n d Efficac y of 
Fecal Micr o bi ota Tra ns pla n tati o n usi n g t he Pe n n Micr o bi o me T hera p y 
Pr o d ucts f or Se vere or Se vere -C o m plicate d/ F ul mi na nt Cl ostri di u m 
d ifficile I nfecti o n 
 
S h ort Title  
P M T f or Se vere -C DI  
I R B N u m ber 
8 3 2 9 6 2  
P h ase  
P hase II  
Met h o d ol o g y  
Ra n d o mize d, o pe n la bel, c o m parati ve  
St u d y D ur ati o n  
T w o years  
St u d y Ce nter  
Pe n n Me dici ne - U ni versit y of Pe n ns yl va nia Healt h S yste m  
O bjecti ves  
Pri m ar y:  T o e val uate t h e effi cac y of fecal micr o bi ota tra ns pla ntati o n 
( F M T) p erf or me d usi n g t he Pe n n Micr o bi o me T hera p y ( P M T) s uite of 
pr o d ucts t o treat s u bjects wit h se vere a n d se vere- c o m plicate d/f ul mi na nt 
Cl ostri di u m difficile  i nfecti o n ( S/ S C/ F-C DI) b y c o m pari n g t he cli nical 
o utc o mes of t hree treat m e nt strate gie s: (1) n o i n vesti gati o nal pr o d uct 
(sta n dar d of car e o nl y); (2) u p per gastr oi ntesti nal a d mi nistrati o n F M T  i n 
a d diti o nal t o sta n dar d of care; ( 3) l o wer gastr oi ntesti nal F M T i n a d diti o n 
t o sta n dar d of care. 
Sec o n d ar y:  T o e val uat e t he safet y of t he P M T  s uite of i n vesti gati o nal 
pr o d ucts f or use i n treati n g  S/ S C/ F -C DI . 
E x pl or at or y:  T o c haract erize ( 1) t he bas eli ne g ut bacterial c o m m u nit y 
c o m p ositi o n a n d h ost i m m u ne p he n ot y p e ass oci ate d wit h S/ S C / F-C DI , 
( 2) t he c h a n ge i n g ut bact erial c o m m u nit y c o m p ositi o n a n d h ost i m m u ne 
p he n ot y p e ass ociat e d wit h eac h of t h e a b o ve treat me nt strate gies , a n d ( 3) 
to deter mi ne t he relati o ns hi p bet wee n bas eli ne g ut bacterial c o m m u nit y 
c o m p ositi o n, h ost i m m u ne p he n ot y pe,  a n d treat me nt o utc o me i n patie nts 
wit h S/ S C /F -C DI.  
N u m ber of 
S u bjects  
Tar get e nr oll me nt: 9 0 s u bjects  


 
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M ai n I ncl usi o n 
a n d E xcl usi o n 
Criteri a  
I ncl usi o n Criteri a: 
1.  O ne or m ore e pis o des of C DI  wit h s y m pt o ms i ncl u di n g b o wel 
m o ve me nts altere d i n fre q ue nc y or c o nsiste n c y fr o m baseli ne. 
2.  St o ol test p ositi ve f or Cl ostri di u m difficile  b y EI A  b y F D A -
clear e d assa y wit hi n 7 da ys pri or t o e nr oll me nt. 
3.  A ge ≥ 1 8 years.  
4.  Meeti n g criteria f or S/ S C/ F -C DI wit hi n 7 2 h o urs of e nr oll me nt, 
w hic h we defi ne as a n y o ne of t he f oll o wi n g: ( 1) l e u k oc yt osis 
wit h peri p heral W B C ≥ 1 5, 0 0 0 cells/ m L; ( 2) h y p ot e nsi o n wit h 
s yst olic bl o o d press ure s ustai ne d < 9 0 m m H g f or t hree or m or e 
h o urs or re q uiri n g press ors; ( 3) pr o vi der d o c u me ntati o n of ile us 
or ra di ol o gic e vi de n ce of b o wel dilati o n or me gac ol o n; ( 4) ac ute 
ki d ne y i nj ur y wit h i ncrease i n baseli ne ser u m creati ni ne le vel b y 
≥5 0 % or ne w dial ysis i nitiati o n; ( 5) ser u m lactate > 2. 2 m m ol/ L; 
or ( 6) ≥ 3 s yste mic i nfla m mat or y res p o nse s y n dr o me ( SI R S) 
criteria ( w hic h i ncl u de h eart rate > 9 0 b eats per mi n ute, 
res pirat or y rate > 2 0 breat hs per mi n ute or Pa C O2 < 3 2 m m H g, 
te m perat ure > 3 8º C or < 3 6º C, W B C > 1 2, 0 0 0 cells/u L , < 4, 0 0 0 
cells/u L , or > 1 0 % i m mat ure ( ba n d) f or ms). 
5.  Recei vi n g a nti bi otic treat me nt f or S/ S C/ F-C DI p er c urre nt I D S A 
g ui deli nes (i. e., va nc o m yci n or fi da x o mici n). 
 
E xcl usi o n Criteri a : 
1.  E vi de nce of c ol o n/s mall b o wel perf orati o n at t he ti me of st u d y 
scree ni n g. 
2.  G oals of care are directe d t o c o mf ort rat her t ha n c urati ve 
meas ures.  
3.  M o derate ( A N C < 1 0 0 0 cells/ u L) or se vere ( A N C  < 5 0 0 cells/ u L) 
ne utr o pe nia. 
4.  K n o w n f o o d aller g y t h at c o ul d lea d t o a na p h yl a xis. 
5.  Pre g n a nc y  
6.  R ecei pt of F M T or e nr oll me nt i n a cli nical trial f or F M T  wit hi n 
t he last 3 m o nt hs. 
7.  C O VI D - 1 9 i nfecti o n, as defi ne d b y a p ositi ve n ucleic aci d or 
a ntige n t est wit hi n t he pri or 1 4 da ys  a n d s y m pt o ms c o nsiste nt 
wit h C O VI D -1 9 i nfecti o n  


 
P M T f or Se vere-C DI  
 
P a ge 8 of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
I n vesti g ati o n al 
Pr o d uct  
1.  Pe n n Micr o bi o me T hera p y –  0 0 1 ( P M T -0 0 1): n o m ore t ha n 
1 5 2 m L  s us pe nsi o n f or rectal e ne ma fr o m 4 0 g h u ma n st o ol, 
c o m prisi n g a t otal of 1 x 1 0 8 – 1 x 1 0 1 2 a naer o bic bacterial 
C F Us/ d ose. 
2.  Pe n n Micr o bi o me T hera p y – 0 0 2 ( P M T- 0 0 2): n o m ore t ha n 
1 5 2 m L s us pe nsi o n f or i ntra gastric, i ntra d u o d e nal, or i ntrajej u nal 
a d mi nistrati o n fr o m 4 0 g h u ma n st o ol, c o m prisi n g 1 x 1 0 8 – 1 x 1 0 1 2 
a naer o bi c bact erial C F Us/ d ose. 
3.  Pe n n Micr o b i o me T hera p y – 0 0 3 ( P M T- 0 0 3): n o m ore t ha n 3 2 
ca ps ules f or oral a d mi nistrati o n fr o m 4 0 g d o n ate d st o ol, 
c o m prisi n g 1 x 1 0 8 – 1 x 1 0 1 2 a naer o bic bacterial C F Us/ d ose. 
 
P M T - 0 0 1, P M T- 0 0 2, P M T- 0 0 3 are p ac k a ge d f or si n gle- d os e 
a d mi nistrati o n . 
 
D ur ati o n of 
a d mi nistr ati o n  
1 0 – 9 0 mi n utes (tar get 3 0 mi n utes) 
Ref ere nce 
t her a p y 
Sta n dar d of care a nti bi otics as pres cri be d b y treati n g cli nicia n. ( M ust be 
c o nc or da nt wit h c urre nt I D S A g ui deli nes t o be eli gi ble f or e nr oll me nt). 
St atistic al 
Met h o d ol o g y 
Pri mar y o utc o m e will be ti me t o res ol uti o n of se vere s y m pt o ms . We will 
c o m pare b ot h F M T gr o u ps (i.e., u p per a n d l o wer gastr oi ntesti nal 
a d mi nistrati o n) i n a g gre gate vers us t he sta n d ar d of care gr o u p via 
c o m peti n g ris k  re gressi o n m o del. 
S af et y 
E v al u ati o ns 
We will m o nit or safet y of a d mi nistrati o n as well as safet y of t he 
i n vesti gati o nal pr o d u cts, i n ter ms of a d vers e e ve nts as liste d i n Secti o n  9 . 
D at a a n d S af et y 
M o nit ori n g Pl a n  
See Secti o n 1 0 . 


 
P M T f or Se vere-C DI  
 
P a ge 9 of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
B ac k gr o u n d a n d St u d y R ati o n ale  
T his st u d y will be c o n d u cte d i n f ull acc or da nce all a p plica ble U ni versit y of Pe n ns yl va nia 
Researc h P olicies a n d Pr oce d ures a n d all a p plica ble Fe d eral a n d st ate la ws a n d  re g ulati o ns 
i ncl u di n g 4 5 C F R 4 6 , 2 1 C F R Parts 5 0 , 5 4 , 5 6 , 3 1 2  a n d G o o d Cli nical Practice : C o ns oli date d 
G ui deli nes a p pr o ve d b y t he I nter n ati o nal C o nfere nce o n Har m o nisati o n (I C H). All e pis o des of 
n o nc o m plia nce will be d oc u me nte d. 
1.  I ntr o d ucti o n 
Fecal micr o bi ota tra ns pla ntati o n ( F M T) is rec o m me n de d treat me nt f or rec urre nt Cl ostri di u m 
difficile  i nfecti o n ( R- C DI) base d o n its s uccess i n m ulti ple trials tar geti n g s u bjects wit h mil d or 
m o derate C DI s y m pt o ms ( Mc D o nal d 2 0 1 8; Kell y BJ 2 0 1 8). T h o u g h t here ha ve bee n o nl y s mall, 
o bser vati o nal st u dies a n d case series of F M T f or p atie nts wit h se vere  a n d se vere 
c o m plicate d/f ul mi na nt C DI , these s u g gest  t hat F M T ma y als o be of be n efit i n se vere a n d se v ere 
c o m plicate d/f ul mi na nt C DI (S/ S C/ F -C DI) as w ell ( Wei n gar de n 2 0 1 3; A gar wal 2 0 1 5; 
Ar o nia dis 2 0 1 5; Fisc her 2 0 1 5; Fisc her 2 0 1 7) . We will perf or m  a ra n d o mize d c o ntr olle d trial t o 
e val uate t he s afet y a n d efficac y of Pe n n Micr o bi o me T hera p y ( P M T)  pr o d ucts f or F M T  i n 
s u bjects w h o meet criteri a f or S/ S C/ F-C DI . T he P M T pr o d ucts c o m prise t hree differe nt 
f or m ulati o ns of F M T  f or oral, e nteri c ( via t u be), or rectal deli ver y. T he S/ S C/ F -C DI trial will 
c o m pare t he effi cac y of  P M T  wit h  sta n dar d of care a nti bi otic t hera p y t o st a n dar d of care 
a nti bi otic t hera p y al o ne. We will als o assess t he safet y of P M T i n t his st u d y p o p ulati o n. Fi n all y, 
we will  c har acterize ke y micr o bi o me a n d h ost i m m u ne p he n ot y p e feat ures ass ociate d wit h 
S/ S C/ F -C DI disease a n d rec o ver y  i n a n e x pl orat or y fas hi o n. T h e pla n ne d st u d y will i nf or m 
treat me nt rec o m me n dati o ns f or S/ S C/ F - C DI a n d la y t h e gr o u n d w or k f or n o vel C DI ris k 
stratificati o n a n d S/ S C/ F - C DI pre ve nti o n strate gi es. 
1. 1.  
B ac k gr o u n d a n d Relev a nt Liter at ure 
As rece ntl y as 2 0 1 5, t he Ce nters f or Disease C o ntr ol a n d Pre ve nti o n ( C D C) i de ntifie d 
Cl ostri di u m difficile i nfecti o n ( C DI) as a n “ ur ge nt” t hreat ass o ciate d wit h u p war ds of 5 0 0, 0 0 0 
i nfecti o ns i n t he U nite d States eac h year a n d res ulti n g i n o ver 1 5, 0 0 0 d eat hs. C DI is 
c haracterize d b y a cli nical s y n dr o me t hat t y picall y i ncl u des l o ose, fre q u e nt b o wel m o ve me nts 
a n d a b d o mi nal pai n, w hi c h occ ur as a res ult of t o xi n pr o d ucti o n b y c ol o ni c C. difficile . C DI 
occ urs i n patie nts c ol o nize d wit h t o xi ge nic C. difficile  a n d i n patie nts w h o ha ve ne wl y ac q uire d 
C. difficile . Esti mates of t he relati ve c o ntri b uti o ns of persiste nt c ol o nizati o n a n d ne w ac q uisiti o n 
t o i nci de nt C DI v ar y. I n b ot h cases, t he pat h o ge nesis of C DI i n v ol ves de pl eti o n of n o n-C. 
difficile  c ol o nic micr o bi ota, altere d bile aci d meta b olis m, ger mi nati o n of (resi de nt or rece ntl y 
i n geste d) C. difficile  s p ores, e x pa nsi o n of a p o p ulati o n of ve getati ve C. difficile , t o xi n 
pr o d ucti o n, a n d c ol o nic i nfla m mati o n.  Ke y c halle n ges ass ociate d wit h C DI i ncl u de its rec urre nce 
after a p pr o priat e a nti bi otic treat me nt ( R - C DI), a n d its pr o gressi o n t o a m ore se vere disease state  
wit h s yste mic si g ns of i nfla m mati o n or e ve n se psis. T he latter, ter m e d se vere or se v ere -
c o m plicate d/f ul mi na nt C DI (S/ S C/ F -C DI) , ofte n re q uires e xte n de d h os pitalizati o ns, ma y re q uire 
c olect o m y, a n d is ass ociate d wit h hi g h rat es of m ortalit y ( K ell y BJ 2 0 1 8). At prese nt, a nti bi otic 
treat me nt is t he rec o m me n de d t hera p y f or earl y R-C DI,  a n d a nti bi otic treat me nt f oll o we d b y 
F M T  is t he rec o m me n de d t hera p y f or l ater R-C DI. A nti bi otic s al o ne are t h e rec o m me n d e d 
t hera p y f or S/ S C/ F- C DI ( Mc D o nal d 2 0 1 8), b ut o bser vati o nal st u dies s u g gest a be nefit f or F M T 
i n t he S/ S C/ F- C DI p o p ulati o n as well (Wei n gar de n 2 0 1 3; A gar wal 2 0 1 5; Ar o nia dis 2 0 1 5; 
Fisc her 2 0 1 5; Fisc her 2 0 1 7). 


 
P M T f or Se vere-C DI  
 
P a ge 1 0  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
1. 2.  
N a m e a n d Descri pti o n of t he I nvesti g ati o n al Pr o d uct 
 
Pe n n Micr o bi o me T her a p y s uite of i n vesti gati o nal pr o d ucts 
 
•  Pe n n Micr o bi o me T her a p y – 0 0 1, hereafter referre d t o as P M T- 0 0 1, 
o  D ose: 1 x 1 0 8 – 1 x 1 01 2 a naer o bic bacterial C F Us deri ve d fr o m 4 0 g of h u ma n 
st o ol dil ute d wit h 1 0 % gl ycer ol i nt o n o m ore t ha n 1 5 2 m L s us pe nsi o n of 
i n vesti gati o nal pr o d u ct. 
o  E ne ma a d mi nistere d rect all y. 
 
•  Pe n n Micr o bi o me T her a p y – 0 0 2, herea fter referre d t o as P M T - 0 0 2, 
o  D ose: 1 x 1 0 8 – 1 x 1 01 2 a naer o bic bacterial C F Us deri ve d fr o m 4 0 g of h u ma n 
st o ol dil ute d wit h 1 0 % gl ycer ol i nt o n o m ore t ha n 1 5 2 m L s us pe nsi o n of 
i n vesti gati o nal pr o d u ct. 
o  S us pe nsi o n a d mi nistere d i ntra gastric, i ntra d u o d e nal, or i ntrajej u nal. 
 
•  Pe n n Micr o bi o me T her a p y – 0 0 3, herea fter referre d t o as P M T - 0 0 3, 
o  D ose: 1 x 1 0 8 – 1 x 1 01 2 a naer o bic bacterial C F Us deri ve d fr o m 4 0 g of h u ma n 
st o ol dil ute d wit h 1 0 % gl ycer ol a n d c o nce ntrate d t o fill n o m ore t ha n 3 2 
ca ps ules . 
o  Ca ps ules t o be a d mi nistere d orall y. 
 
C he mical Na me a n d Str u ct ure:  
P M T - 0 0 1: Fecal Micr o bi ot a f or Tra ns pla nt, e ne m a pr o d uct 
P M T - 0 0 2: Fecal Micr o bi ota f or  Tra ns pla nt, s us pe nsi o n pr o d uct 
P M T - 0 0 3: Fecal Micr o bi ota f or Tra ns pla nt, ca ps ul e pr o d uct 
 
T he t hree i n v esti gati o nal pr o d ucts, P M T- 0 0 1, 0 0 2, 0 0 3, are c o m p os e d of d o nate d st o ol fr o m 
healt h y d o n ors t h at meet t he d o nati o n criteria. T h e st o ol sa m ple is c o m p ose d of a p pr o xi matel y 
7 5 % water a n d 2 5 %  or ga nic a n d i n or ga nic s oli ds. T y picall y, 1 g of st o ol c o ntai ns a p pr o xi matel y 
1 0 9 bacterial cells. T he st o ol sa m ple is s u bse q ue ntl y pr ocesse d wit h p h os p h ate- b uffere d sali ne 
( P B S) c o ntai ni n g 1 0 % gl ycer ol a n d f or m ulate d as a s us pe nsi o n f or P M T- 0 0 1 a n d P M T- 0 0 2 or 
c o nce ntr ate d a n d e nca ps ulate d  f or P M T- 0 0 3. 
1. 2. 1.  N o n -Cli nic al D at a  
F M T as a tr eat me nt m o d alit y f or C DI di d n ot ta ke t he c o n ve nti o nal pat h of dr u g d e vel o p me nt. 
Fecal tra ns pla nts see m t o date as f ar bac k as 4t h ce nt ur y C hi na, a n d ha v e rece ntl y bec o me 
rec o m me n de d t h era p y f or R- C DI o n t he basis of s e veral ra n d o mize d trials ( Mc D o nal d 2 0 1 8; va n  
N o o d 2 0 1 3; Y o u n gster 2 0 1 6; Kell y C R 2 0 1 6; Ka o 2 0 1 7), e ve n as t here re mai ns si g nifica nt 
heter o ge n eit y a m o n g F M T pr o d ucts. T here is n o esta blis he d sta n dar d f or n o n- cli nical testi n g of 
F M T pr o d ucts gi ve n u n certai nt y as t o w hat micr o bial feat ures deter mi ne p ote nc y ( B oja n o va 
2 0 1 6). T he treat me nt pr ot oc ol o utli ne d here is bas e d o n t he res ults p u blis he d fr o m pri or st u dies 
t hat ha ve dri ve n t he st a n dar ds a d o pte d i n o ur R- C DI a n d S/S C/ F - C DI pr ot oc ols ( Ha milt o n 2 0 1 2; 
Kell y BJ 2 0 1 8; Ca m mar ota 2 0 1 7 ; Krajice k 2 0 1 8). 


 
P M T f or Se vere-C DI  
 
P a ge 1 1  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
1. 2. 2.  Cli nic al D at a  t o D ate 
T here is n o a v aila ble cli nical researc h d ata t o date o n t he i n vesti gati o nal pr o d ucts P M T - 0 0 1, 0 0 2, 
or 0 0 3. F M T has b ee n est a blis he d as effecti ve a n d is rec o m me n de d f or treat me nt of m ulti pl y 
rec urre nt C DI o n t he b asis of se ver al ra n d o mize d c o ntr olle d trials ( Mc D o nal d 2 0 1 8; va n  N o o d 
2 0 1 3; Y o u n gster J A M A 2 0 1 4; Kell y C R 2 0 1 6; Ka o 2 0 1 7). O bser vati o nal st u dies ha ve s u g geste d 
t hat F M T ma y ha v e si milar efficac y f or S/ S C/ F- C DI ( Wei n gar de n 2 0 1 3; A gar wal  2 0 1 5; 
Ar o nia dis 2 0 1 5; Fisc her 2 0 1 5; Fisc her 2 0 1 7). See Ta ble 1  f or a s u m mar y of t he ris ks descri b e d 
i n t he literat ure. 




 
P M T f or Se vere -C DI  
 
P a ge 1 3  of 4 4  
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
 
 
1. 3.  
D ose R ati o n ale 
T here are n o pre -cli nical or cli nical data f or t he P M T s uite of F M T pr o d u cts t o i nf or m o pti mal 
d ose. H o we v er, t her e ar e e xte nsi ve o bser vati o nal st u dies a n d se veral ra n d o mize d trials t hat 
s u g gest a n F M T d ose d eri ve d fr o m 3 0- 1 0 0 g of h u ma n st o ol is effecti ve t o treat R-C DI 
( Ca m mar ota 2 0 1 4; va n N o o d 2 0 1 3; Y o u n gster J A M A 2 0 1 4; Kell y C R 2 0 1 6). Pr ot oc ols f or t he 
treat me nt of S/ S C/ F-C DI ha ve t y picall y use d si milar F M T d os es as pr ot oc ols f or t he treat me nt of 
R- C DI , b ut ha v e all o we d f or re p eat F M T a d mi nistrati o n at s h ort i nter vals if cli nicall y i n dicat e d 
( Wei n gar de n 2 0 1 3; A gar wal 2 0 1 5; Ar o nia dis 2 0 1 5; Fisc her 2 0 1 5; Fisc her 2 0 1 7). See Ta ble 1  f or 
a s u m mar y of d os es d escri be d i n t he literat ure.  
 
T he S/ S C/ F -C DI trial  pr ot oc ol all o ws f or re p eat P M T d osi n g at 3- d a y  i nter vals, u p t o a 
ma xi m u m of t hree d oses, if s u bjects fail t o meet pre -esta blis he d criteria f or cli nical 
i m pr o ve me nt. T he re p eat a d mi nistrati o n strate g y is base d o n t he o bser v ati o n t hat s o me patie nts 
wit h S/ S C/ F -C DI fail t o i m pr o ve wit h i nitial F M T a d mi nistrati o n b ut d o i m pr o ve aft er re peat 
a d mi nistrati o n ( Wei n gar de n 2 0 1 3; A gar w al 2 0 1 5; Ar o nia dis 2 0 1 5; Fisc her 2 0 1 5; Fisc her 2 0 1 7). 
2.  St u d y  O bjecti ves  
2. 1. 
Pri m ary O bjective  
T o e val uate t he effi cac y of fecal micr o bi ota tra ns pla ntati o n ( F M T) p erf or me d usi n g t he Pe n n 
Micr o bi o me T her a p y ( P M T) s uite of pr o d ucts t o treat s u bjects wit h se vere a n d se vere-
c o m plicate d/f ul mi na nt Cl ostri di u m difficile  i nfecti o n ( S/ S C/ F-C DI) b y c o m pari n g t h e cli nical 
o utc o mes of t hree treat m e nt strate gies: ( 1) n o i n vesti gati o nal pr o d uct (st a n d ar d of care o nl y); ( 2) 
u p per gastr oi ntesti nal a d mi nistrati o n F M T i n a d diti o nal t o sta n dar d of care; ( 3) l o wer 
gastr oi ntesti nal F M T i n a d diti o n t o sta n dar d of care. 
2. 2. 
Sec o n d ary O bjective  
T o e val uate t he s afet y of t he P M T s uite of i n vesti gati o nal pr o d ucts f or use i n treati n g S/ S C/ F-
C DI.  
2. 3.  
E x pl or at ory O bjective 
T o c har acterize ( 1) t he b aseli ne g ut bacterial c o m m u nit y c o m p ositi o n a n d h ost i m m u ne 
p he n ot y p e ass ociat e d wit h S/ S C/ F- C DI, ( 2) t he c h a n ge i n g ut bacterial c o m m u nit y c o m p ositi o n 
a n d h ost i m m u ne p he n ot y p e ass ociate d wit h eac h of t he a b o ve treat me nt strate gies, a n d ( 3) t o 
deter mi ne t he r elati o ns hi p bet wee n b aseli ne g ut b acterial c o m m u nit y c o m p ositi o n , h ost i m m u ne 
p he n ot y p e,  a n d treat me nt o utc o me i n patie nts wit h S/ S C/ F -C DI.  
 
3.  I n vesti g ati o n al Pl a n 
3. 1. 
Ge ner al Desi g n  
We will perf or m  a r a n d o mize d, c o ntr olle d, o pe n la bel trial. S u bjects will be scree ne d t o e v al uate 
if t he y meet i ncl usi o n criteria f or s e vere or se v ere c o m plicate d/f ul mi na nt C DI. If eli gi ble, 
s u bjects will partici pate i n t he i nf or me d c o nse nt pr ocess. F oll o wi n g i nf or me d c o nse nt, s u bjects 


 
P M T f or Se vere-C DI  
 
P a ge 1 4  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
will be ra n d o mize d t o o ne o f t hree ar ms: (1) sta n d ar d of care a nti bi otics ( n o i nter ve nti o n), (2) 
P M T - u p per GI a d mi nistrati o n pl us sta n dar d of care a nti bi otics, or (3) P M T -l o wer GI 
a d mi nistrati o n pl us sta n dar d of care a nti bi otics. S u bjects will t he n be eli gi ble  t o recei v e u p t o 
t w o ad diti o nal a d mi nistrati o ns of P M T ( u p per or l o wer GI) at 3- d a y  ( +/- 1 da y)  i nter vals if t he y 
d o n ot meet pre -d efi ne d criteria f or cli nical i m pr o ve me nt ( see Secti o n  3. 2. 1  bel o w). S u bjects will 
be f oll o we d u ntil 1 8 0 da ys after t heir l ast P M T d ose. 
3. 1. 1.  Scree ni n g P h ase  
P ote ntial s u bjects will be i de ntifie d b y acti ve s ur v eilla nce f or i n patie nts at partici pati n g h os pitals 
wit h p ositi ve C.  difficile  EI A st o ol testi n g. A p ositi ve st o ol EI A test f or C.  difficile  will pr o m pt 
re vie w of t h e electr o nic h ealt h rec or d t o deter mi ne w het her a p ot e ntial s u bject ma y meet 
i ncl usi o n/e x cl usi o n criteria. If a p ote ntial s u bject ma y meet i ncl usi o n/e x cl usi o n criteria, t he st u d y 
tea m will c o ntact t he s u bject’s i n patie nt care tea m t o ascertai n w h et her t he care t ea m has a n y 
o bjecti o n t o t he st u d y tea m a p pr oac hi n g t he p ote ntial s u bject. If t he p ote ntial s u bject’s care tea m 
has n o o bjecti o n, t he p ote ntial s u bject ( or t heir d esi g nate d me di cal decisi o n -ma ker) will be 
c o ntacte d t o disc uss partici pati o n, fi nal scree ni n g f or i ncl usi o n/e x c l usi o n criteria will be 
perf or me d, a n d i nf or me d c o nse nt will be o btai ne d. A rec or d of all scree n e d s u bjects will be 
mai ntai ne d t o e val uate t h e fr e q u e nc y of i d e ntifie d e x cl usi o ns or care-tea m o bjecti o ns. T he st u d y 
will als o be o pe n t o patie nts tra nsferr e d t o a partici pati n g h os pital w h o ha d p ositi ve ( F D A 
clear e d) C.  difficile  EI A st o ol testi n g at a n o utsi de h os pital pri or t o tra nsfer, s o l o n g as a rec or d 
of t he p ositi ve test ca n be o btai ne d. Care tea ms at t he partici pati n g h os pitals ma y refer s uc h 
patie nts f or partici p ati o n.  
3. 1. 2.  St u d y I nter ve nti o n P h ase  
All S/ S C/ F -C DI trial i nter ve nti o ns will be perf or m e d i n patie nt at t he liste d st u d y site h os pitals. 
D uri n g t h e i nter ve nti o n p eri o d, f oll o wi n g i nf or me d c o nse nt a n d ra n d o mizati o n, s u bjects i n eit her 
t he u p per GI ( P M T- 0 0 2 or P M T-0 0 3) or l o wer GI ( P M T - 0 0 1) i nter ve nti o n ar m will recei ve 
si n gle- d os e P M T a d mi nistrati o n, wit h P M T f or m ulati o n  a n d r o ute of a d mi nistrati o n (s us pe nsi o n 
f or e ne m a, s us pe nsi o n f or e nteric d eli ver y, or oral ca ps ules) det er mi ne d per ra n d o mizati o n a n d 
stratificati o n sc he me (Secti o n 3. 1. 6 ). A d mi nistrati o n of t he pr o d uct will ta k e place o v er 1 0 t o 9 0 
mi n utes (tar get 3 0 mi n utes). S u bjects ra n d o mize d t o P M T will be eli gi ble  t o recei v e u p t o t w o 
a d diti o nal a d mi nistrati o ns of P M T ( b y cli nicall y a p pr o priate r o ute of a d mi nistrati o n) at 3- da y 
( +/- 1 da y) i nter vals, if t h e y fail t o meet criteria f or cli nical i m pr o ve me nt  (Secti o n 3. 2. 1 ). 
A nti bi otics prescri be d as part of r o uti ne cli nical care f or C DI will n ot be altere d  b y t he 
i nter ve nti o n. 
3. 1. 3.  P ost -P M T A d mi nistr ati o n m o nit ori n g: Be dsi de f or 6 0 Mi n utes  
S u bjects will be m o nit ore d at 3 0 a n d 6 0 mi n utes f oll o wi n g c o m pleti o n of P M T a d mi nistrati o n. 
S u bjects will be vis uall y o bser ve d f or si g ns of as pirati o n or ot her res pirat or y distress ( P M T- 0 0 2 
a n d P M T- 0 0 3), a b d o mi n al pai n, v o miti n g, ot her si g ns of aller gic reacti o n, a n d c ha n ges i n vi tal 
si g ns ( P M T- 0 0 1, P M T- 0 0 2, a n d P M T- 0 0 3). Vital si g ns (te m perat ure, h eart rate, res pirat or y rate, 
bl o o d press ure, a n d o x y g e n sat urati o n) will be c h ec ke d . T he f oll o wi n g vital si g n c ha n ges will be 
rec or d e d if o bser v e d, a n d will pr o m pt n otificati o n of t he pri mar y cli nical care tea m: ( 1) h eart rate 
increas e or decrease b y greater t ha n or e q u al t o 3 0 beats per mi n ute ; ( 2) res pirat or y rate i n crease 
or decr ease b y greater t h a n or e q ual t o 1 0 breat hs per mi n ute or if res pirat or y rate dr o ps b el o w 1 0 
or i ncreases a b o v e 2 5 (if res pirat or y r ate n ot alrea d y o utsi de t hese ra n ges) ; ( 3) te m perat ure: 


 
P M T f or Se vere-C DI  
 
P a ge 1 5  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
i ncreas e or decrease b y greater t ha n or e q u al t o 2 de grees Fa hre n heit, or if te m perat ure dr o ps 
bel o w 9 6° F or i n creases a b o ve 1 0 0. 4° F (if te m perat ure n ot alrea d y o utsi de t hese ra n ges); ( 4) 
o x y ge n s at urati o n decrease b y great er t ha n or e q u al t o 5 % (s ustai ne d f or m ore t ha n 2 0 sec o n ds) 
or if o x y ge n sat ur ati o n dr o ps bel o w 9 0 % ( o n c urre nt a m o u nt of o x y ge n d eli vere d, s ustai ne d f or 
m ore t ha n 2 0 sec o n ds) ; ( 5) bl o o d press ure d ecreas e b y m ore t ha n 3 0 m m H g s yst olic or 1 5 m m H g 
diast olic, or if bl o o d press ure dr o ps bel o w 9 0/ 6 0 (if bl o o d press ure n ot alrea d y o utsi de t hese 
ra n ges). 
3. 1. 4.  P ost - P M T A d mi nistr ati o n m o nit ori n g: D ail y f or 3 D a ys after  
A d mi nistr ati o n/ E nr oll me nt  
T he s u bject will be m o nit ore d e ver y cale n dar d a y f or t hree d a ys after eac h P M T a d mi nistrati o n 
i n or der t o assess t heir eli gi bilit y f or re p eat u p t o 2 a d diti o nal d oses of P M T at 3 da ys after t he 
first a d mi nistrati o n a n d 3 da ys after a sec o n d a d mi nistrati o n (if gi ve n), as w ell as t o assess f or 
a d verse e ve nts . If t h e s u bject c o nti n ues t o meet criteria f or s e vere or se v ere-c o m plicate d diseas e 
wit hi n t he pri or 2 4 h o urs at 3 da ys after t he i nitial a d mi nistrati o n  a n d t he n 3 da ys after t he sec o n d 
a d mi nistrati o n (if gi ve n), t he s u bject will be eli gi ble f or a  re peat d ose of P M T (sa me f or m ulati o n 
as per i nitial ra n d o mizati o n) . If P M T a d mi nistrati o n is u na ble t o be perf or me d at 3 or 6 da ys 
f oll o wi n g t he first a d mi nistrati o n, t he n a d mi nistrati o n wit hi n 1 cale n dar da y bef ore or aft er t h ose 
da ys will be per mitte d. Assess me nt  f or eli gi bilit y f or a n a d diti o nal d ose will be perf or me d o n t he 
da y of re p eat a d mi nistrati o n. F or s u bjects i n t he n o n- P M T ar m, m o nit ori n g will be perf or me d 
dail y f or t hree d a ys aft er e nr oll me nt f or a d v erse e ve nt assess me nt. 
3. 1. 5.  P ost - P M T A d mi nistr ati o n F oll o w-U p  
F oll o wi n g a s u bject’s fi n al P M T a d mi nistrati o n  or e nr oll me nt f or t h ose i n t he n o n-P M T ar m , 
s u bjects e nter t he f oll o w u p p hase. D uri n g t his p h ase, t he f oll o wi n g will occ ur: ( 1) w hile 
re mai ni n g i n p atie nt, dail y ma xi m u m te m perat ure, n u m ber of b o wel m o ve me nts, a n d a n y 
e pis o des of e mesis will be rec or de d ( b ase d o n electr o nic me dical rec or d) f or 7 cale n d ar da ys 
p ost- F M T  or p ost-e nr oll me nt f or t he n o n-P M T ar m ; ( 2) i n pre parati o n f or disc har ge fr o m t he 
h os pital, s u bjects will rec or d dail y te m p erat ure, n u m ber of b o wel m o ve m e nts, a n d a n y e pis o des 
of e mesis f or 7 d a ys p ost last F M T/ p ost-e nr oll me nt  (s u bjects will be gi ve n a s y m pt o m diar y 
car d; a di gital t her m o met er will als o be pr o vi de d); ( 3) s u bjects will be c o nt acte d b y tele p h o n e or 
i n- pers o n f or a n i nter vie w f oc use d o n p ote ntial a d verse e v e nts at 7 da ys ( or ne xt w or ki n g da y, 
n ot t o e x cee d 1 0 da ys ) after fi nal F M T  or aft er e nr oll me nt f or n o n -P M T ar m ; ( 4) s u bjects will be 
c o ntacte d b y tele p h o ne or i n - pers o n at 3 0 d a ys ( +/- 3 da ys) after fi n al F M T or after e nr oll me nt 
f or n o n-P M T ar m  f or a n i nter vie w f oc us e d o n p ote ntial a d vers e e ve nts; ( 5) s u bjects will be 
c o ntacte d b y tele p h o ne or i n - pers o n at 9 0 d a ys ( +/- 7 da ys) after fi n al F M T  or after e nr oll me nt 
f or n o n-P M T ar m  f or a n i nter vie w f oc us e d o n p ote ntial a d vers e e ve nts; ( 6) s u bjects will be 
c o ntacte d b y tele p h o ne or i n - pers o n at 1 8 0 d a ys ( +/- 7 da ys) after fi nal F M T or after e nr oll me nt 
f or n o n-P M T ar m  f or a n i nter vie w f oc us e d o n p ote ntial a d vers e e ve nts. 
 
Tele p h o ne vers us i n- pers o n f oll o w- u p will be deter mi ne d base d o n s u bject prefere nce. (If 
s u bjects pref er t o be see n i n pers o n, b ut ha ve bee n disc har ge d fr o m t he h os pital, a cli nic visit 
wit h a st u d y tea m  me m b er will be arra n ge d). All F M T reci pie nts ( or t heir s urr o gates) will be 
gi ve n c o ntact i nf or m ati o n f or t he st u d y c o or di nat or. As detaile d a b o v e, s u bjects will be f oll o we d 
f or 1 8 0 da ys f oll o wi n g last i n vesti gati o nal pr o d uct a d mi nistrati o n or after e nr oll me nt f or n o n-
P M T ar m . All s u bjects will be als o pr o vi de d a st u d y c o nt act tele p h o n e n u m ber o n a c o p y of t he 


 
P M T f or Se vere-C DI  
 
P a ge 1 6  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
i nf or me d c o nse nt f or m, i n case c o n cer ns f or a d verse e ve nt or ot her q uesti o ns arise. S u bjects will 
als o be per mitte d t o i nitiate electr o nic c o m m u nicat i o n wit h t he st u d y t ea m, alt h o u g h pla n n e d 
f oll o w u p visits will be c o n d ucte d b y tele p h o ne or i n pers o n. T he st u d y tea m ma y reac h o ut t o 
s u bjects electr o nicall y if diffic ulties arise i n reac hi n g t he s u bject b y t ele p h o ne i n or der t o 
sc he d ule visits, b ut st u d y-relate d q u esti o ns will n ot be as ke d electr o nicall y. S u bjects will be 
classifie d as l ost t o f oll o w u p if at least t hree atte m pts are ma de at c o ntact wit h o ut s uccess; 
h o we ver, me di cal r ec or d re vie w will still be use d t o o btai n f oll o w u p i nf or mati o n o n t hes e 
s u bjects. If a s u bject is eli gi ble a n d e nr olle d a s ec o n d ( or greater) ti me, t he n t heir s u bse q ue nt 
f oll o w u p will be c o n d ucte d acc or di n g t o t he s c he d ule set b y t heir m ost rece nt e nr oll me nt, a n d 
a n y re mai ni n g f oll o w u ps fr o m earlier e nr oll me nt(s) will n ot be perf or me d.  
3. 1. 6.  All oc ati o n t o I nter ve nti o n al Gr o u p 
Stratifie d ra n d o mizati o n will be perf or me d b ase d o n se verit y cat e g or y (se v ere vers us se vere 
c o m plicate d) i n a 2: 1 f as hi o n (t w o t o t he F M T i nter ve nti o n ( P M T- 0 0 1, 0 0 2, or 0 0 3) a n d o ne t o 
t he sta n dar d of car e c o ntr ol gr o u p). T he ra n d o mizati o n sc he d ule will be pre pare d usi n g a 
ra n d o m-size bl oc k strate g y t o e ns ur e bala n ce t hr o u g h o ut t he trial. Pri or t o e nr oll me nt of t he first 
s u bject, a ra n d o mizati o n ta ble will be pr o d uce d f or eac h cate g or y usi n g Stata statistica l s oft ware 
a n d t he “ Rall oc” p ac k a ge.  
 
If s u bjects ar e k n o w n t o ha ve e nteral access (eit her acti vel y recei vi n g ca ps ule me dicati o ns a n d/ or 
n utriti o n b y m o ut h or vi a pre- e xisti n g e nteric t u be, as prescri be d  b y t he cli nical care tea m ), t h e y 
will u n der g o a sec o n d ra n d o miz ati o n i n a 1: 1 fas hi o n bet wee n all ocati o n t o F M T b y e ne m a (i.e., 
P M T - 0 0 1) or F M T b y u p per e nteral a d mi nistrati o n (i.e., P M T - 0 0 2 or P M T - 0 0 3). S u bjects w h o 
are r a n d o mize d t o F M T b ut w h o lac k e nteral access  or w h o are d ee me d t o ha ve ile us (i.e., e nteral 
me dicati o ns a n d n utriti o n hel d) b y t h e cli nical care tea m will recei v e P M T - 0 0 1 e ne ma. S u bjects 
w h o are ra n d o mize d t o F M T b ut ha ve b o wel disc o nti n uit y will o nl y be eli gi ble f or t he 
i nter ve nti o n ar m t hat c oi nci des wit h t heir pres u m e d si de of C DI (e. g. if C DI i n resi d ual 
rect u m/c ol o n, o nl y eli gi ble f or P M T- 0 0 1). Pri or t o e nr oll me nt of t he first s u bject, a 
ra n d o mizati o n ta ble will be pr o d uce d f or t he s ec o n d (r o ute of a d mi nistrati o n) ra n d o mizati o n 
usi n g R statistical s oft ware . 
 
S u bjects ra n d o mize d t o rece i ve F M T, a n d t h e n t o recei v e F M T via u p p er d eli ver y will ha ve t he 
decisi o n ma de bet w ee n P M T - 0 0 2/ P M T- 0 0 3 acc or di n g t o h o w ot her me di cati o ns a n d n utriti o n 
are bei n g d eli vere d (i.e., t h ose recei vi n g n utriti o n a n d me dicati o ns via e nteric t u be will recei ve 
P M T - 0 0 2 s us pe nsi o n, a n d t h ose eati n g f o o d a n d recei vi n g oral me di cati o ns will recei ve P M T-
0 0 3 ca ps ules). Cr oss -o v er bet wee n P M T -0 0 2 a n d P M T -0 0 3 will be per mitte d if re p eat F M T 
a d mi nistrati o n is i n dicate d, b ut a s u bject’s m o de of n utriti o n a n d me dicati o n a d mi nistrati o n has 
c ha n ge d.  Cr oss -o v er bet wee n P M T - 0 0 1 a n d P M T- 0 0 2/ 0 0 3 will be per mitte d if re peat F M T 
a d mi nistrati o n is i n dicate d, b ut a s u bject has l ost e nteral access a n d is u n a ble t o t olerate oral 
me dicati o ns.  
 
F or a gra p hical re pr ese nt ati o n of t he all ocati o n t o t he i nter ve nti o nal gr o u ps, refer t o Fi g ure 1 . 
 


 
P M T f or Se vere -C DI  
 
P a ge 1 7  of 4 4  
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
 
Fi g ure 1: All oc ati o n t o I nter ve nti o n al Gr o u p Fl o w Di a gr a m 


 
P M T f or Se vere -C DI  
 
P a ge 1 8  of 4 4  
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
 
3. 2.  
St u dy E n d p oi nts 
3. 2. 1.  Pri m ar y St u d y E n d p oi nts  
T he pri mar y o utc o me is r es ol uti o n of s y m pt o ms ass ociate d wit h S/ S C/ F-C DI , liste d bel o w. T h e 
pri mar y o utc o me will be satisfie d w he n t he s u bject is disc har ge d fr o m t he h os pital ( n ot t o 
h os pice or palliati ve care) or, w hile t he s u bject re mai ns h os pitalize d,  w he n t he f oll o wi n g criteria 
are met f or 7 2 h o urs: 
•  
If ra di ol o g y st u d y or st u dies perf or me d, ile us/dilati o n / me gac ol o n eit her n ot n ote d or 
n ote d as res ol ve d ( electr o nic me dical rec or d s earc h w or ds : “ile us”, “ dilate d”, “ dilati o n”, 
or “ me gac ol o n”) 
•  
Ile us/ me gac ol o n eit her n ote d as res ol ve d b y a n y pr o vi der d oc u me nt ati o n or n ot n ote d 
(electr o ni c me dical r ec or d searc h w ords: “ile us”, “ me gac ol o n ”) 
•  
W B C < 1 5, 0 0 0 cells/ u L  
•  
Ser u m cr eati ni ne decr eas e d, u nc h a n ge d, or i ncreas e d b y ≤0. 2 m g/ d L o ver 7 2  h o urs (if n ot  
recei vi n g c o nti n u o us r e n al re place me nt t hera p y ( C R R T) or he m o dial ysis ( H D)) 
•  
Lactate  ≤2. 2 m m ol/ L (if meas ure d b y cli nical care tea m) 
•  
N o  vas o press ors  use d  (i ncl u di n g  e pi ne p hri n e,  n ore pi ne p hri ne,  p he n yle p hri n e,  or  
vas o pressi n) 
•  
Te m perat ur e < 3 8. 5 ° C a n d ≥3 5. 6° C  
•  
< 8 b o wel m o ve me nts per da y a n d < 6 0 0 m L u nf or me d st o ol (if v ol u me rec or de d) 
•  
Meeti n g fe w er t ha n 3 s yste mic i nfla m mat or y res p o nse s y n dr o me ( SI R S) criteria (i.e., n o 
m ore t ha n t w o of t he f oll o wi n g: heart rat e > 9 0 beats per mi n ute ; res pirat or y rate > 2 0 
breat hs per mi n ute or Pa C O 2 < 3 2 m m H g; t e m perat ure > 3 8º C or < 3 6º C ; WB C > 1 2, 0 0 0 
cells/u L , < 4, 0 0 0 cells/u L , or > 1 0 % i m mat ure ( ba n d) f or ms) 
 
Disc har ge t o h os pice, nee d f or b o w el s ur ger y (c olect o m y, di verti n g ile ost o m y), a n d d eat h will 
c o u nt as fail ur es. S u bjects w h o u n der g o b o w el s ur ger y aft er i nitial P M T a d mi nistrati o n will n ot be 
eli gi ble f or a d diti o nal a d mi nistrati o ns.  
3. 2. 2.  Sec o n d ar y St u d y E n d p oi nts  
Sec o n dar y e n d p oi nts i ncl u de: 
•  
All -ca use m ortalit y at 3 0 - a n d 6 0- da ys f oll o wi n g l ast F M T 
•  
C olect o m y or di verti n g il e ost o m y wit hi n 3 0 da ys after last F M T 
•  
C u m ulati ve da ys of h os pitalizati o n fr o m e nr oll me nt u ntil 3 0 da ys after F M T  
•  
C u m ulati ve  da ys i n i nte nsi ve care u nit fr o m e nr oll me nt u ntil 3 0 da ys aft er l ast F M T 
•  
Bact ere mia fr o m e nr oll m e nt u ntil 3 0 da ys after last F M T 
•  
Re peat h os pital a d missi o n  wit hi n 6 0 da ys of disc h ar ge fr o m i n de x h os pitalizati o n 
3. 2. 3.  Pri m ar y S af et y E n d p oi nts 
 
T he pri mar y safet y e n d p oi nts will i ncl u de:  
•  F re q ue nc y of s olicite d a d verse e v e nts ( A Es ) 
•  Fre q u e nc y of s eri o us a d v erse e v e nts (S A Es ) 
•  Fre q u e nc y of A Es of s pecial i nterest ( A E SIs ) 


 
P M T f or Se vere-C DI  
 
P a ge 1 9  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
 
See S ecti o n 9  f or a d diti o nal details o n a d vers e e v e nt defi niti o ns. 
 
M o nit ori n g p ost- P M T a d mi nistrati o n will occ ur i n t hree p has es:  
3. 2. 3. 1.  
P ost -P M T A d mi nistr ati o n m o nit ori n g: Be dsi de f or 6 0 Mi n utes  
Safet y e n d p oi nts f or all r o utes of a d mi nistrati o n will i ncl u de w orse ne d a b d o mi nal pai n, fe ver, 
tac h ycar dia, a n d h y p ote nsi o n (Secti o n 3. 2. 1 ). Safet y e n d p oi nts f or u p p er e nteral deli ver y (i.e., 
P M T - 0 0 2 or P M T- 0 0 3) will i ncl u de e vi de nce of as pirati o n (i ncl u di n g re d uce d o x y ge n s at urati o n, 
tac h y p nea, or res pir at or y distress, as defi ne d a b o ve). 
3. 2. 3. 2.  
P ost -P M T A d mi nistr ati o n or P ost- E nr oll me nt m o nit ori n g: D ail y f or 3 D a ys  
Safet y e n d p oi nts f or all r o utes of a d mi nistrati o n will i ncl u de ne w ile us, w orse ne d le u k oc yt osis, 
ne w/ w orse n e d ac ut e ki d ne y i nj ur y, n e w/ w ors e ne d ser u m lactate ele vati o n, n e w/ w orse n e d fe v er, 
or w orse n e d diarr h ea. T h e defi niti o ns of eac h a d v erse e v e nt are gi ve n i n Secti o n 3. 2. 1 . T he  
a d verse e ve nts c o m m o nl y e n c o u nter e d i n pri or F M T st u dies were gi ve n i n Ta ble 1 . 
3. 2. 3. 3.  
P ost -P M T or P ost -E nr oll me nt A d mi nistr ati o n F oll o w -U p  
Safet y e n d p oi nts assesse d at t he 7- da y f oll o w- u p a n d all s u bse q ue nt f oll o w- u ps will i ncl u de 
fe ver, di arr h ea, na us ea, a n d v o miti n g. Safet y e n d p oi nts assesse d  at t he 3 0- d a y, 9 0- da y, a n d 1 8 0-
da y f oll o w - u ps will i ncl u de e vi de nce of ne w meta b olic disease, i ncl u di n g h y p er gl yce mia, 
t h yr oi d diseas e, wei g ht gai n or l oss. 
4.  St u d y P o p ul ati o n a n d D ur ati o n of P artici p ati o n  
4. 1. 
I ncl usi o n Criteri a 
1.  O ne or m ore e pis o des of C DI wit h s y m pt o ms i ncl u di n g b o wel m o ve m e nts altere d i n 
fre q ue n c y or c o nsiste n c y fr o m baseli ne. 
2.  St o ol test p ositi ve f or Cl ostri di u m difficile  b y EI A  b y F D A -cleare d assa y wit hi n 7 da ys 
pri or t o e nr oll me nt.  
3.  A ge ≥ 1 8 years  
4.  Meets a n y o ne of t he liste d criteri a f or se v ere or s e vere -c o m plicate d /f ul mi na nt disease 
(see Ta bl e 2  bel o w) wit hi n 7 2 h o urs of e nr oll me nt.  
5.  Recei vi n g a nti bi otic treat me nt f or S/ S C/ F -C DI p er c urre nt I D S A g ui deli nes.  
 
E nr oll me nt criteria det ails:  
1.  M ust  eit her  meet  ≥1  criteria  i n  se vere  cate g or y or i n se vere c o m plicate d cate g or y t o be 
e nr olle d. 
2.  If t he s u bject meets crit eria i n b ot h cate g ories, stratif y t o t he hi g h er se verit y cate g or y 
(se ver e c o m plicate d). 
3.  Detaile d e nr oll me nt criteria defi niti o ns (f or T a ble 2 ): 
a. W B C ≥1 5, 0 0 0 cells/ u L  – if a n y v al ue i n t he ti me peri o d meets t his defi niti o n. 
b.  H y p ote nsi o n wit h s yst oli c bl o o d press ure s ustai ne d < 9 0 m m H g f or t hree or m ore 
h o urs or re q uiri n g v as o press ors   (e pi ne p hri n e, n ore pi ne p hri ne, p he n yle p hri ne, or 
vas o pressi n). 


 
P M T f or Se vere-C DI  
 
P a ge 2 0  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
c. Ac ute ki d ne y i nj ur y – i n creas e i n s er u m creati ni n e le vel b y ≥5 0 % or ne w dial ysis 
i nitiati o n. 
i. If a baseli ne ser u m creati ni ne val ue is n ot a vaila ble, ac ute ki d ne y i nj ur y will 
be defi ne d as a ser u m creati ni ne > 1. 5 m g/ d L. 
d.  Te m perat ur e ≥3 8. 5 ° C  or < 3 5. 6° C - o ne val ue n ee de d i n ti me peri o d. 
e. Ile us, b o wel dilati o n  or me gac ol o n . 
i. Ile us: If n ot e d i n a n y pr o vi der d oc u me ntati o n or pr o ble m list (searc h w or ds 
“ile us”) O R  
ii. If t he w or ds “ dilate d ” “ dilati o n” or “ile us” are n ote d i n a ra di ol o g y re p ort  
o n i ntesti nes/c ol o n, or if “ me gac ol o n ” n ote d. 
f. Lactate > 2. 2 m m ol/ L - if a n y v al ue i n t he ti me peri o d meets t his defi niti o n. 
g.  SI R S criteria : 
i. Heart r ate > 9 0 b eats per mi n ute  
ii. Res pirat or y rate > 2 0 breat hs per mi n ute or Pa C O 2 < 3 2 m m H g 
iii. Te m perat ur e > 3 8º C or < 3 6º C 
i v. W B C > 1 2, 0 0 0 cells/ u L , < 4, 0 0 0 cells/u L , or > 1 0 % i m mat ure ( ba n d) f or ms 
 
Use Ta ble 2  b el o w t o deci de if t he s u bject meets criteria f or e nr oll me nt a n d t heir 
stratificati o n cate g or y (se vere vers us se vere-c o m plicate d). 
T a ble 2 : E nr oll me nt a n d str atific ati o n criteri a  
 
W B C 
≥1 5, 0 0 0 
cells/ u L  
Ac ute 
ki d ne y 
i nj ur y 
H y p o -
te nsi o n 
Ile us, 
b o w el 
dil ati o n , or 
me g ac ol o n  
Te m p 
≥3 8. 5 ° C  
or 
< 3 5. 6° C  
Use of v as o -
press ors / 
h y p ote nsi o n  
L act ate 
> 2. 2 
m m ol/ L  
≥3 
SI R S 
criteri a  
W B C ≥1 5, 0 0 0 
cells/ u L  
S  
S  
S C  
S C  
S C  
S C  
S C  
S C  
Ac ute ki d ne y  
i nj ur y 
S  
S  
S C  
S C  
S C  
S C  
S C  
S C  
Ile us or 
a b d o mi n al 
diste nsi o n  
S C  
S C  
S C  
S C  
S C  
S C  
S C  
S C  
Te m p ≥3 8. 5 
° C or 
< 3 5. 6° C   
S C  
S C  
S C  
S C  
S C  
S C  
S C  
S C  
Use of 
v as o press ors / 
h y p ote nsi o n  
S C  
S C  
S C  
S C  
S C  
S C  
S C  
S C  
L act ate > 2. 2 
m m ol/ L 
S C  
S C  
S C  
S C  
S C  
S C  
S C  
S C  
≥3 SI R S 
criteri a  
S C  
S C  
S C  
S C  
S C  
S C  
S C  
S C  
S = Se vere cate g or y  
S C = Se vere -c o m plicate d cate g or y  
W B C = w hite bl o o d cell c o u nt  
SI R S = s yste mic i nfla m mat or y res p o nse s y n dr o me  
4. 2. 
E xcl usi o n Criteri a  
1.  E vi de nce of c ol o n/s mall b o wel perf orati o n at t he ti me of st u d y scree ni n g. 
2.  G oals of care are dir ecte d t o c o mf ort rat her t ha n c urati ve meas ures.  


 
P M T f or Se vere-C DI  
 
P a ge 2 1  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
3.  M o derate ( A N C < 1 0 0 0 cells/ u L) or se vere ( A N C < 5 0 0 cells/ u L) ne utr o p e nia. 
4.  K n o w n f o o d aller g y t h at c o ul d lea d t o a na p h yl a xis. 
5.  Pre g n a nc y  
a. F or s u bjects of c hil d beari n g p ote ntial (a ges 1 8 t o 5 5), t he s u bject m ust h a ve a 
ne gati ve uri ne pre g n a nc y test wit hi n 4 8 h o urs of c o nse nt a n d n o m ore t ha n 4 8 h o urs 
pri or t o first pr o d uct a d mi nistrati o n. 
6.  Recei pt of F M T or e nr oll me nt i n a cli nical trial f or F M T wit hi n t he last 3 m o nt h s. 
7.  C O VI D -1 9 i nf ecti o n, as defi n e d b y a p ositi ve n ucleic aci d or a nti ge n test wit hi n t he pri or 
1 4 da ys a n d s y m pt o ms c o nsiste nt wit h C O VI D- 1 9 i nfecti o n 
4. 3. 
S u bject Recr uit m e nt  
P ote ntial s u bjects will be i de ntifie d b y acti ve s ur v eilla nce f or i n patie nts wit h p ositi ve C.  difficile  
EI A st o ol testi n g at si x partici pati n g Pe n n M e dici n e U ni versit y of Pe n ns yl v a nia Healt h S yste m 
h os pitals (see Secti o n 4. 5 ). A p ositi ve st o ol EI A test f or C.  difficile  wi ll pr o m pt re vie w of t he 
electr o nic h ealt h rec or d t o deter mi ne w het h er a p ote ntial s u bject ma y m eet  i ncl usi o n/e x cl usi o n 
criteria. If a p ote ntial s u bject ma y meet  i ncl usi o n/e x cl usi o n criteria, t he st u d y tea m will c o ntact 
t he s u bject’s i n patie nt care tea m t o as certai n w h et her t he care t ea m has a n y o bjecti o n t o t he st u d y 
tea m e nr olli n g t h e p ote ntial s u bject. T he  p ote ntial s u bject ( or t heir d esi g n ate d me dical decisi o n -
ma ker) will be c o ntacte d t o disc uss partici pati o n . If t he p ote ntial s u bject is eli gi ble a n d wa nts t o 
partici pate , i nf or m e d c o nse nt will be o btai ne d. At t his ti me, s u bjects of c hil d beari n g p ote ntial 
(a ges 1 8 t o 5 5) will ha ve a uri ne pr e g na nc y t est perf or me d. If a uri n e pre g n a nc y test is n ot a ble t o 
be perf or me d or if it is p ositi ve, t he p ote ntial s u bjects will be e x cl u de d. A rec or d of all scree ne d 
s u bjects will be mai ntai ne d t o e val uate t he fre q ue nc y of i de ntifie d e x cl usi o ns or care-tea m 
o bjecti o ns. T he st u d y will als o be o pe n t o patie nts tra nsferre d t o a p artici pati n g h os pital w h o ha d 
p ositi ve C.  difficile  EI A st o ol testi n g at a n o utsi de h os pital pri or t o tra nsfer, s o l o n g as a rec or d of 
t he p ositi ve test ca n be o btai ne d. Care tea ms at t he partici pati n g h os pitals ma y refer s uc h p atie nts 
f or partici pati o n. 
4. 4.  
D ur ati o n of St u dy P artici p ati o n 
T he s u bjec ts will partici p ate i n t he st u d y f or 1 8 0 d a ys ( +/- 7 d a ys) aft er t he last a d mi nistrati o n of 
t he P M T pr o d uct. St u d y partici pati o n will c o ncl u de wit h t he 1 8 0 - da y f oll o w-u p visit (i n - pers o n 
or b y tel e p h o ne). 
4. 5.  
T ot al N u m ber of S u bjects a n d Sites 
Recr u it me nt will be perf or me d at o ne site wit h si x partici pati n g Pe n n Me di ci ne U ni versit y of 
Pe n ns yl va nia Healt h S yst e m l ocati o ns: ( 1) t he H os pital of t he U ni versit y of Pe n ns yl va nia ( H U P), 
( 2) Pe n n -Pres b yteria n M e dical Ce nter ( P P M C) , ( 3) Pe n ns yl va ni a H os pital ( PA H) , ( 4) La n caster 
Ge ner al H os pital ( L G H), ( 5) C hester C o u nt y H os pital ( C C H), a n d ( 6) Pe n n Me dici ne Pri ncet o n 
Me dical Ce nter ( P M P M C).  E nr oll me nt tar gets 9 0 s u bjects, wit h 3 0 ra n d o mize d t o eac h ar m. 
4. 6.  
V ul ner a ble P o p ul ati o ns 
C hil dre n, fet uses, or ne o nates ar e n ot i ncl u de d i n t his researc h st u d y b eca use t he gastr oi ntesti nal 
micr o bi o me is si g nifica ntl y diff ere nt bet w ee n c hil dre n a n d a d ults. Pre g n a nt w o me n will n ot be 
eli gi ble t o partici p ate i n t his st u d y d u e t o u n k n o w n ris ks of F M T i n pre g n a nc y. Pris o ners will be  
eli gi ble t o partici p ate i n t his st u d y.  Disa ble d, ec o n o micall y - or e d ucati o nall y- disa d v a nta ge d 
pers o ns will be eli gi ble f or e nr oll me nt. V ul nera ble p o p ulati o ns will be pr otecte d via t he i nf or me d 


 
P M T f or Se vere-C DI  
 
P a ge 2 2  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
c o nse nt pr ocess, w hic h e ns ures t hat e nr olle d s u bjects or s u bje ct-s urr o gates u n dersta n d st u d y 
ris ks a n d be nefits. V ul nera ble p o p ulati o ns will be pr otecte d fr o m c oerci o n beca use t h ere is n o 
fi na ncial be n efit t o partici pati o n i n t he st u d y. 
5.  St u d y I nter ve nti o n 
5. 1. 
Descri pti o n  
Pe n n Micr o bi o me T her a p y s uite of i n vesti gati o nal pr o d ucts ha ve bee n des cri be d pre vi o usl y i n 
S ecti o n 1. 2 . T he pr o d uct la bel will i ncl u de ( 1) a u ni q ue d ose i de ntifier (a n d barc o de), ( 2) t h e 
P M T f or m ulati o n ( P M T- 0 0 1, P M T- 0 0 2, or P M T- 0 0 3), ( 3) a d o n or i de ntifier, ( 4) t he d ate of 
d o nati o n a n d d ose pr ocessi n g, a n d ( 5) t he e x pirati o n date.  
5. 2. 
I nterve nti o n Re gi m e n 
T his st u d y is  a ra n d o mize d, c o ntr olle d, o pe n la b el trial. S u bjects will be scree ne d t o e v al uate if 
t he y meet i ncl usi o n criteria f or se vere or s e vere c o m plicate d/f ul mi na nt C DI. If eli gi ble, s u bjects 
will partici pate i n t he i nf or me d c o nse nt pr o cess. F oll o wi n g i nf or me d c o nse nt, s u bjects will be 
ra n d o mize d t o o ne of t hr ee ar ms: ( 1) sta n dar d of care a nti bi otics ( n o i nter v e nti o n), ( 2) P M T-
u p per GI a d mi nistrati o n pl us sta n dar d of care a nti bi otics, or ( 3) P M T- l o wer GI a d mi nistrati o n 
pl us sta n dar d of care a nti bi otics. I n t he i nter v e nti o n ar ms, s u bjects will t he n be eli gi ble t o recei ve 
u p t o t w o a d diti o nal a d mi nistrati o ns of P M T ( u p per or l o wer GI) at 3- da y i nter vals if t he y d o n ot 
meet pre -d efi ne d criteria f or cli nical i m pr o ve me nt  f or 2 4 h o urs (see S ecti o n 2. 1 ). If P M T 
a d mi nistrati o n is u na ble t o be perf or me d o n t he sc he d ule d da ys ( 3-da y i nter vals), a d mi nistrati o n 
wit hi n 1 cale n dar d a y bef ore or after t h ose d a ys will be per mitte d. S u bject s will be assesse d f or 
eli gi bilit y f or a n a d diti o n al d ose o n t he da y of re p eat a d mi nistrati o n. S u bjects will be f oll o we d 
u ntil 1 8 0 da ys aft er t heir last P M T d ose. 
 
D uri n g t h e i nter ve nti o n p eri o d, f oll o wi n g i nf or me d c o nse nt a n d ra n d o mizati o n ( Secti o n  3. 1. 2 ), 
s u bjects i n eit her i nter ve nti o n ar m ( n ot t he sta n dar d of care c o ntr ol ar m) will recei ve si n gle- d os e 
P M T a d mi nistrati o n, wit h P M T f or m ulati o n deter mi ne d per ra n d o mizati o n. A d mi nistrati o n of 
t he pr o d uct is descri b e d i n Secti o n 5. 7  bel o w. S u bjects will be eli gi ble t o recei ve u p t o t w o 
a d diti o nal a d mi nistrati o ns of P M T ( per sa me ra n d o mizati o n) at 3 da ys a n d 6 da ys ( +/-1 d a y) 
after t he i nitial d ose  if t h e y fail t o meet criteria f or cli nical i m pr o ve me nt (Secti o n  3. 2. 1 ) a n d as 
l o n g as t he y d o n ot ha v e b o wel s ur ger y. A nti bi otics prescri be d as p art of r o uti ne cli nical care f or 
C DI will n ot be altere d b y t he i nter v e nti o n . 
5. 3. 
Recei pt  
T he prescri be d f or m ulati o n of t he i n vesti gati o nal pr o d uct [ P M T- 0 0 1 ( E ne ma), P M T- 0 0 2 
( S us pe nsi o n) or P M T - 0 0 3 ( Ca ps ule)] will be pac k a ge d  o n dr y ice fr o m t he P M T ma n ufact uri n g 
facilit y at t he U ni versit y of Pe n ns yl va ni a. T he ti me of rel ease fr o m fr oze n st ora ge will be 
d oc u me nte d a n d i ncl u d e d i n P M T pr o d uct pac ka gi n g. P M T pr o d ucts will be deli vere d b y st u d y 
staff or c o urier i n si n gle d oses. U p o n recei pt of t h e pr o d uct b y t he I n v esti gat or, pac k a gi n g ( ba gs 
f or P M T- 0 0 1 a n d P M T- 0 0 2; ca ps ule c o ntai ners f or P M T- 0 0 3) will be i ns pecte d f or i nte grit y, a n d 
pr o d uct will be c hec ke d t o e ns ure t hat it is still fr oze n a n d l o g ge d i n t he i n v esti gati o nal pr o d u ct 
acc o u nta bi lit y l o g. T h e i n vesti gati o nal pr o d u ct la bel will als o be c hec k e d t o e ns ure t hat t he 
pr o per pr o d u ct is recei ve d, a n d t o e ns ure t hat t he pr o d uct has n ot e x pire d. 


 
P M T f or Se vere-C DI  
 
P a ge 2 3  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
5. 4.  
St or a ge 
I n v esti gati o nal pr o d ucts are tr a ns p orte d fr oze n o n dr y ice b y c o urier or st u d y staff t o t he cli nical 
l ocati o n. I n v esti gati o nal pr o d ucts are tra ns p orte d i n c o ntai ners la b elle d a n d mai ntai ne d at a 
te m perat ur e i n acc or da n ce wit h fe deral a n d l ocal re g ul ati o ns f or t he tra ns p ort of bi ol o gical 
pr o d ucts. 
 
At t he cli nical l ocati o n , a d mi nistrati o n of P M T - 0 0 1 or P M T - 0 0 2 will be i nitiate d wit hi n 1 8 0 t otal 
mi n utes of pr o d uct releas e fr o m fr oze n st ora ge. At t he cli nical site, a d mi nistrati o n of P M T- 0 0 3 
will be i nitiate d wit hi n 1 2 0 mi n utes of pr o d uct rel ease fr o m fr oze n st ora ge. T he ti me of release 
fr o m fr oze n st ora ge will be i ncl u de d i n P M T pr o d uct pac ka gi n g ( Secti o n 5. 3 ). 
 
P M T - 0 0 1 a n d P M T- 0 0 2 d oses will be t ha we d at r o o m te m perat ure f or 3 0- 6 0 mi n utes pri or t o 
a d mi nistrati o n. P M T -0 0 3 will re mai n o n dr y ice u ntil t he ti me of a d mi nistrati o n.  
 
A n y d os es release d  fr o m fr oze n st ora ge b ut n ot a d mi nistere d wit hi n t he all otte d ti me (1 8 0 
mi n utes f or P M T- 0 0 1 a n d P M T- 0 0 2, 1 2 0 mi n utes f or P M T- 0 0 3) after release (e. g., d ue t o d ela ys 
i n tra ns p ort) will be destr o ye d. I n s uc h cases, eli gi ble s u bjects will be offere d a n ot her d os e, a n d 
t he releas e pr ocess will be re-i nitiate d. 
5. 5.  
Pre p ar ati o n a n d P ac k a gi n g 
Pre parati o n of t he t hree i n vesti gati o nal pr o d u cts [ P M T- 0 0 1 ( E ne ma), P M T- 0 0 2 ( S us pe nsi o n), 
a n d P M T- 0 0 3 ( Ca ps ule)] will be perf or me d at t he P M T ma n ufact uri n g facilit y at t he U ni ver sit y 
of Pe n ns yl va ni a.  P M T - 0 0 1 a n d P M T- 0 0 2 are p ac ka ge d i n E V A b a gs s uita ble f or st ora ge at  
< - 7 0° C (tar get - 8 0° C). P M T- 0 0 3 is e nca ps ulate d wit hi n t hree neste d gel ati n ca ps ules (sizes 0 0, 
0, a n d 1), t he n pac ka ge d i n a n H D P E ca ps ule c o ntai ner s uita ble f or st ora ge at < - 7 0° C (tar get  
- 8 0° C). T he t hree i n vesti gati o nal pr o d u cts will be pac ka ge d i n si n gle d os es. 
5. 6. 
Bli n di n g  
Neit her s u bjects  n or i n v esti gat ors will  be bli n de d. 
5. 7. 
A d mi nistr ati o n a n d Acc o u nt a bility  
T he i n vesti gati o nal pr o d ucts will be c hec k e d o n recei pt as a b o v e (Secti o n 5. 3 ). Pri or t o 
a d mi nistrati o n, P M T - 0 0 1 a n d P M T- 0 0 2 will be all o we d t o t ha w at r o o m te m perat ure ( 5 0° F - 
7 5 ° F) f or 3 0- 6 0 mi n utes. T he ba g ma y be m assa ge d d uri n g t ha wi n g. A d mi nistrati o n of P M T - 0 0 1 
a n d P M T- 0 0 2 will be gi n wit hi n  6 0 mi n utes of t ha wi n g. Pri or t o a d mi nistrati o n, P M T - 0 0 3 will be 
ke pt o n dr y ice; P M T- 0 0 3 will n ot be t ha we d bef ore a d mi nistrati o n. 
 
As state d i n Secti o n 5. 4 , t he t otal ti me fr o m releas e fr o m fr oze n st ora ge at t he ma n ufact uri n g 
facilit y t o i nitiati o n of a d mi nistrati o n will n ot e x cee d 1 8 0 mi n utes f or P M T- 0 0 1 a n d P M T- 0 0 2; it 
will n ot e x c ee d 1 2 0 mi n utes f or P M T - 0 0 3. 
 
T he d urati o n of a d mi nistrati o n will ta ke 1 0 - 9 0 (t ar get 3 0) mi n utes f or all pr o d ucts. 
A d mi nistrati o n of all t hree P M T pr o d ucts will be perf or me d b y a lice ns e d p h ysicia n, a d va nce d 
me dical practiti o ner, or n urse. 
 


 
P M T f or Se vere-C DI  
 
P a ge 2 4  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
P M T - 0 0 1 will be a d mi nistere d b y e n e ma  usi n g a n a p pr o ve d e n e ma a d mi nistrati o n kit. P M T- 0 0 2 
will be a d mi nistere d via i ntra gastric , i ntra d u o d e nal, or i ntrajej u nal r o ute, c o nti n ge nt o n t he 
prese nce of a pre -e xisti n g a p pr o ve d i ntra gastric , i ntra d u o de nal, or i ntrajej u nal t u be. P M T- 0 0 3 
will be a d mi nistere d orall y. P ost- pr oce d ure m o nit ori n g will be perf or m e d  as descri be d 
else w her e. F or eac h i n vesti gati o nal pr o d uct d ose, t he pr o d uct i de ntit y, d os e tar gete d f or 
a d mi nistrati o n , t he date a n d ti me a d mi nistere d, r o ute of a d mi nistratio n, s u bject i de ntit y, q ua ntit y 
of pr o d uct act uall y a d mi nistere d, a n d q ua ntit y of pr o d uct re mai ni n g will b e rec or de d via a 
sta n dar d f or m. 
5. 8. 
S u bject C o m pli a nce M o nit ori n g  
P ost- pr oce d ure m o nit ori n g will be perf or me d  as descri be d else w here  (Secti o ns 3. 1. 3  t o 
Secti o n  3. 1. 5 ). F or eac h i n vesti gati o nal pr o d u ct d ose, t he pr o d uct i de ntit y, d ose tar gete d f or 
a d mi nistrati o n, t he date a n d ti me a d mi nistere d, r o ute of a d mi nistrati o n, s u bject i de ntit y, q ua ntit y 
of pr o d uct act uall y a d mi nistere d, a n d q ua ntit y of pr o d uct re mai ni n g will b e rec or de d via a 
sta n dar d f or m. T h e st u d y tea m  will rec or d if t h e s u bject was n ot a ble t o t ol erate or recei ve t he 
f ull d ose d ue t o a d vers e e ve nts or beca use t he all o we d d urati o n of a d mi nistrati o n was e x cee d e d. 
5. 9. 
Ret ur n or Destr ucti o n of I nvesti g ati o n al Pr o d uct  
F or P M T - 0 0 1 or P M T- 0 0 2, t he v ol u me of i n vesti gati o nal pr o d u ct will be rec or de d at t he ti me of 
dr u g pr o d uct ma n uf act uri n g, a n d t h e v ol u me of resi d ual i n vesti gati o nal pr o d uct (if a n y) will be 
rec or d e d b y t he lice ns e d me dical pr of essi o nal perf or mi n g a d mi nistrati o n aft er a d mi nistrati o n is 
c o m plete d ( o r st o p pe d). F or P M T - 0 0 3, t he n u m ber of ca ps ules i n t he d os e will be rec or d e d at t he 
ti me of dr u g pr o d uct ma n ufact uri n g, a n d t h e n u m ber of re mai ni n g ca ps ules (if a n y) will be 
rec or d e d b y t he lice ns e d me dical pr of essi o nal perf or mi n g a d mi nistrati o n aft er a d ministrati o n is 
c o m plete d ( or st o p pe d). A n y re mai ni n g i n vesti gati o nal pr o d uct will be dis p ose d of at t he cli nical 
site. 
6.  St u d y Pr oce d ures  
T he st u d y pr oce d ures ar e als o o utli ne d i n detail bel o w . T he sc he d ule of st u d y pr oce d ures is 
prese nte d  i n Ta bl e 3 . 
6. 1. 
Scree ni n g a n d E nr oll m e nt  
6. 1. 1.  S ur veill a nce Test Re vie w  
P ote ntial s u bjects will be i de ntifie d b y acti ve s ur v eilla nce f or i n p atie nts at partici pati n g h os pitals 
wit h p ositi ve C.  difficile  EI A st o ol testi n g.  
6. 1. 2.  Me dic al Rec o r d Re vie w f or I ncl usi o n/ E xcl usi o n Criteri a  
A p ositi ve st o ol EI A test f or C.  difficile  will pr o m pt re vie w of t he electr o nic healt h rec or d t o 
deter mi ne w het her a p ote ntial s u bject ma y meet  i ncl usi o n/e x cl usi o n criteria (Secti o ns 4. 1  a n d 4. 2 ). 
6. 1. 3.  I nf or me d C o nse nt 
If  a  p ote ntial  s u bject  m a y  meet  i ncl usi o n/e x cl usi o n  criteria,  t he  st u d y tea m  will  c o ntact  t he  
s u bject’s i n patie nt car e tea m t o ascertai n w h et her t he care tea m has a n y o bjectio n t o t he st u d y t ea m 
e nr olli n g t he p ot e ntial s u bject. T he  p ote ntial s u bject ( or t heir d esi g nate d me dical decisi o n -ma k er) 
will  be  c o ntacte d  t o  disc uss  partici pati o n . If t he  p ote ntial  s u bject  is  eli gi ble  a n d  w a nts  t o  


 
P M T f or Se vere-C DI  
 
P a ge 2 5  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
partici pate , i nf or me d c o nse nt will be o btai ne d. Su bjects  of c hil d beari n g p ote ntial will be teste d 
usi n g a uri ne pre g n a nc y t est if p ossi ble; if uri ne pre g n a nc y t est p ositi ve or n ot p ossi ble, p ote ntial 
s u bjects will be e x cl u de d. A r ec or d of all s cree n e d s u bjects will be m ai ntai ne d t o e v al uate t h e 
fre q ue n c y of i de ntifie d e x cl usi o ns or care-tea m o bjecti o ns. 
6. 1. 4.  E nter al Access C hec k  
T he e nr olle d s u bject’s e nteral access will be re vie we d t o det er mi ne w h et her t he s u bject q ualifies 
f or ra n d o mizati o n bet wee n u p per a n d l o wer gastr oi ntesti nal deli ver y of i n vesti gati o nal pr o d u ct. 
6. 1. 5.  R a n d o miz ati o n 
F oll o wi n g e nr oll me nt, ra n d o mizati o n will be perf or me d as per S ecti o n 3. 1. 6 . 
6. 2. 
St u dy I nterve nti o n P h ase  
6. 2. 1.  P M T Pr o d uct Recei pt  
After t he treat me nt pla n is deter mi ne d b y ra n d o mizati o n, t he P M T pr o d uct t o w hic h t he s u bject is 
assi g ne d will be pre pare d a n d recei ve d as d escri b e d a b o ve ( Secti o n 5. 3 ). 
6. 2. 2.  A d mi nistr ati o n  
D uri n g t h e i nter ve nti o n p eri o d, f oll o wi n g i nf or me d c o nse nt a n d ra n d o mizati o n, s u bjects i n eit her 
i nter ve nti o n ar m ( n ot t he sta n dar d of care c o ntr ol ar m) will recei v e si n gl e-d ose P M T 
a d mi nistrati o n, wit h t he P M T f or m ulati o n deter mi ne d per ra n d o mizati o n. A d m i nistrati o n of t he 
pr o d uct ( P M T- 0 0 1, P M T- 0 0 2, or P M T- 0 0 3) will ta ke place o ver 1 0 t o 9 0 mi n utes (tar get 3 0 
mi n utes). S u bjects will be eli gi ble t o r ecei ve u p t o t w o a d diti o nal a d mi nistrati o ns of P M T at 3-
da y i nter vals, if t he y f ail t o meet criteria f or cli nical i m pr o ve me nt. A nti bi otics prescri b e d as part 
of r o uti ne cli nical care f or C DI will n ot be altere d b y t he i nter v e nti o n.  
6. 2. 3.  P ost -I nter v e nti o n 6 0 mi n utes 
S u bjects will be m o nit ore d f or a p eri o d of 6 0 mi n utes f oll o wi n g c o m pleti o n of P M T 
a d mi nistrati o n. S u bjects will be vis uall y o bser v e d f or si g ns of as pirati o n or ot her res pirat or y 
distress, a b d o mi nal pai n, v o miti n g, ot her si g ns of aller gic reacti o n, a n d c ha n ges i n vital si g ns. 
Vital si g ns (te m perat ure, heart r ate, res pirat or y rate, bl o o d press ure, a n d o x y ge n s at urati o n) will 
be c hec ke d i m me diatel y p ost -a d mi nistrati o n a n d at 3 0 a n d 6 0 mi n utes f oll o wi n g c o m pleti o n of 
P M T a d mi nistrati o n. T he f oll o wi n g vital si g n c ha n ges will be rec or de d if o bser ve d, a n d will 
pr o m pt n otificati o n of t he pri mar y cli nical care tea m: ( 1) i ncrease or d ecrease b y greater t ha n or 
e q ual t o 3 0 beats per mi n ute; ( 2) res pirat or y rat e i ncreas e or decrease b y greater t ha n or e q u al t o 
1 0 breat hs per mi n ute or if res pirat or y rate dr o ps b el o w 1 0 or i ncreases a b o ve 2 5 (if res pirat or y 
rate n ot alr ea d y o utsi de t hese ra n ges); ( 3) t e m perat ure: i ncrease or d ecrease b y greater t ha n or 
e q ual t o 2 de grees Fa hre n heit, or if te m perat ure dr o ps bel o w 9 6° F or i ncreases a b o ve 1 0 0. 4° F (if 
te m perat ur e n ot alrea d y o utsi de t hese ra n ges); ( 4) o x y ge n s at urati o n decrease b y greater t ha n or 
e q ual t o 5 % (s ustai ne d f or m ore t ha n 2 0 sec o n ds) or if o x y ge n sat urati o n dr o ps bel o w 9 0 % ( o n 
c urre nt a m o u nt of o x y ge n deli vere d, s ustai ne d f or m ore t ha n 2 0 sec o n ds); ( 5) bl o o d press ure 
decrease b y m or e t ha n 3 0 m m H g s yst olic or 1 5 m m H g diast olic, or if bl o o d press ure dr o ps 
bel o w 9 0/ 6 0 (if bl o o d press ure n ot alrea d y o utsi de t hese ra n ges). 


 
P M T f or Se vere-C DI  
 
P a ge 2 6  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
6. 2. 4.  P ost -I nter v e nti o n 3 D a ys 
T he s u bject will be m o nit ore d e ver y cale n dar d a y f or t hree d a ys after eac h P M T a d mi nistrati o n 
i n or der t o assess t heir eli gi bilit y f or re p eat u p t o 2 a d diti o nal d oses of P M T at 3 da ys after t he 
first a d mi nistrati o n a n d 3 da ys after a sec o n d a d mi nistrati o n (if gi ve n) as w ell as t o assess f or 
a d verse e ve nts . If t h e s u bject c o nti n ues t o meet criteria f or s e vere or se v ere-c o m plicate d diseas e 
wit hi n t he pri or 2 4 h o urs at 3 after t h e i nitial a d mi nistrati o n a n d 3 da ys after a sec o n d 
a d mi nistrati o n (if gi ve n)  (see S ecti o n 3. 2. 1 ) a n d if t he s u bject has n ot u n der g o ne b o wel s ur ger y, 
t he s u bject will be eli gi bl e f or a n a d diti o nal d ose of P M T (f or m ulati o n per re peat ass ess me nt of 
s u bject’s m o de of n utriti o n a n d me dicati o n – i.e., c ha n ge i n f or m ulati o n is all o we d). If P M T 
a d mi nistrati o n is u na ble t o be perf or me d o n t he sc he d ule d da ys, a d mi nistrati o n wit hi n 1 cale n dar 
da y b ef or e or after t h ose da ys will be per mitte d. S u bject s will be assesse d f or eli gi bilit y f or a n 
a d diti o nal d ose o n t he da y of re peat a d mi nistrati o n. S u bjects i n t he n o n- P M T ar m will be 
m o nit ore d e ver y cale n d ar da y f or t hree da ys after e nr oll me n t t o assess f or a d verse e v e nts. 
6. 3. 
St u dy F oll o w - u p P h ase  
6. 3. 1.  F oll o w- u p 7 d a ys 
F oll o wi n g a s u bject’s fi n al P M T a d mi nistrati o n or f oll o wi n g e nr oll me nt i n t he n o n- P M T ar m , 
s u bjects e nter t he f oll o w u p p hase. D uri n g t his p h ase, vital si g ns,  s y m pt o ms, a n d la b orat or y 
val ues s u g gesti ve of a d v erse e v e nts will be trac k e d a n d rec or de d. S pecificall y, w hile re m ai ni n g 
i n patie nt, dail y ma xi m u m te m perat ure, n u m b er of b o wel m o ve me nts, a n d a n y e pis o des of e mesis 
will be rec or d e d ( bas e d o n electr o nic me di cal rec or d) f or 7 cale n d ar da ys p ost -F M T  or p ost-
e nr oll me nt i n n o n- P M T ar m . I n pre parati o n f or dis c har ge, s u bj ects will be gi ve n a diar y f or 
trac ki n g dail y te m per at ur e, n u m ber of b o w el m o ve me nts, a n d a n y e pis o d es of e mesis f or 7 d a ys 
p ost last F M T  or p ost-e nr oll me nt (s u bjects will be gi ve n a s y m pt o m diar y car d; a di gital 
t her m o meter will als o be pr o vi de d). Su bjects will be c o ntact e d b y tele p h o n e or i n - pers o n f or a n 
i nter vie w f oc us e d o n p ote ntial a d vers e e ve nts at 7 da ys after fi nal F M T or p ost -e nr oll me nt f or 
n o n- P M T ar m ; t he first atte m pt at c o ntact will be ma de b y t he first w or ki n g da y at 7 da ys or lat er 
( n ot t o e x cee d 1 0 da ys) f oll o wi n g t he final F M T. (I n cas e of tele p h o n e f oll o w- u p, t he 7-da y 
s y m pt o m diar y car d will be tra nscri b e d b y st u d y st aff o ver t he p h o ne/a n d or c ollecte d d uri n g t he 
i n- pers o n f oll o w- u p visit. See S ecti o n 6. 3. 2 ). Tele p h o ne vers us i n- pers o n f oll o w- u p will be 
deter mi ne d bas e d o n s u bject prefer e nce. If s u bjects prefer t o be see n i n pers o n, b ut ha ve bee n 
disc har ge d fr o m t he h os pital, a cli nic visit wit h a st u d y tea m me m b er will be arra n ge d.  
 
T o a d dress t he e x pl orat or y ai ms, dail y s wa bs of a v aila ble st o ol a n d peri -rect al s wa bs will be 
ta ke n f or micr o bi o me a n al ysis f or 7 d a ys p ost-F M T  or p ost-e nr oll me nt f or n o n-P M T ar m . If 
bl o o d t hat was c ollecte d f or cli nical p ur p os es w o ul d ot her wise be discar de d, it will be ca pt ure d 
f or i m m u ne res p o nse p h e n ot y pi n g. St o ol s peci me ns will be o btai ne d b y placi n g fl o c ke d n yl o n 
s wa bs i n st o ol if a vaila ble (e. g. i n ba g of fecal ma na ge me nt s yste m). I n a d diti o n, peri-rectal 
s wa bs will be o btai ne d if p ossi ble. Bl o o d will be c ollecte d fr o m resi d ual material a v aila ble i n 
E D T A (“ p ur ple t o p”) v ac utai ner t u bes alrea d y c oll ecte d i n t he cli nical la b orat or y. If s u bjects 
ha ve bee n disc har ge d fr o m t he h os pital, n o s wa bs will be c ollecte d. If n o resi d ual bl o o d is 
a vaila ble, or if s u bjects h a ve bee n disc har ge d fr o m t he h os pital, n o bl o o d will be c ollecte d. St o ol, 
peri -rectal a n d bl o o d s peci me n a nal ysis will be directe d b y t he pri nci pal i n vesti gat or a n d st u d y 
tea m. 


 
P M T f or Se vere-C DI  
 
P a ge 2 7  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
6. 3. 2.  F oll o w- u p 3 0 d a ys 
S u bjects will be c o ntacte d a gai n b y tele p h o ne or i n- pers o n at 3 0 d a ys ( +/- 3 da ys) after fi nal 
F M T or p ost-e nr oll me nt f or n o n- P M T ar m f or a n i nter vie w f oc us e d o n p ote ntial a d vers e e ve nts. 
Tele p h o ne vers us i n- pers o n f oll o w- u p will be deter mi ne d base d o n s u bject prefere nce. (If 
s u bjects pref er t o be see n i n pers o n, b ut ha ve bee n disc har ge d fr o m t he h os pital, a cli nic visit 
wit h a st u d y tea m me m b er will be arra n ge d).  
6. 3. 3.  F oll o w- u p 9 0 d a ys 
S u bjects will be c o ntacte d b y tele p h o n e or i n- p ers o n  at 9 0 da ys ( +/- 7 d a ys) after fi n al F M T or 
p ost-e nr oll me nt f or n o n- P M T ar m f or a n i nter vi e w f oc use d o n p ote ntial a d verse e v e nts. 
Tele p h o ne vers us i n- pers o n f oll o w- u p will be deter mi ne d base d o n s u bject prefere nce. (If 
s u bjects pref er t o be see n i n pers o n, b ut ha ve bee n disc har ge d fr o m t he h os pital, a cli nic visit 
wit h a st u d y tea m me m b er will be arra n ge d).  
6. 3. 4.  E n d - of-st u d y visit at 1 8 0 d a ys 
T he st u d y will c o n cl u de after s u bjects are c o ntact e d b y t ele p h o ne or i n- pers o n at 1 8 0 da ys ( +/- 
1 0 da ys) after fi nal F M T or p ost-e nr oll me nt f or n o n- P M T ar m f or a fi nal i nter vie w f o c use d o n 
p ote ntial a d verse e ve nts . Tele p h o ne vers us i n- pers o n f oll o w- u p will be deter mi ne d base d o n 
s u bject prefere n ce. (If s u bjects pref er t o be see n i n pers o n, b ut ha ve b ee n disc har ge d fr o m t he 
h os pital, a cli nic visit wit h a st u d y tea m me m ber will be arra n ge d).  
 
S u bjects will be per mitte d t o i nitiate electr o nic c o m m u nicati o n wit h t he st u d y tea m, alt h o u g h 
pla n ne d f oll o w u p visits will be c o n d ucte d b y tele p h o ne or i n pers o n. T h e st u d y tea m ma y reac h 
o ut t o s u bjects electr o nicall y if diffi c ulties arise i n reac hi n g t he s u bj ect b y t ele p h o ne i n or der t o 
sc he d ule visits, b ut st u d y-relate d q u esti o ns will n ot be as ke d electr o nicall y. S u bjects will be 
classifie d as l ost t o f oll o w u p if at least t hree atte m pts are ma de at c o ntact wit h o ut s uccess; 
h o we ver, me di cal r ec or d re vie w will still be use d t o o btai n f oll o w u p i nf or mati o n o n t hese 
s u bjects. If a s u bject is eli gi ble a n d e nr olle d a s ec o n d ( or greater) ti me, t he n t heir s u bse q ue nt 
f oll o w u p will be c o n d ucte d acc or di n g t o t he s c he d ule set b y t heir m ost rece nt e nr oll me nt, a n d 
a n y re mai ni n g f oll o w u ps fr o m earlier e nr oll me nt(s) will n ot be perf or me d.  
6. 4. 
Resc ue T her a py  
If a s u bject is t h o u g ht t o ha ve a se v er e a d verse e v e nt it will be rec or d e d b y t he st u d y tea m a n d 
t he s u bject will be f oll o w e d u ntil res ol uti o n a n d referre d t o s u bject’s pri mar y cli nical care tea m. 
I n t he cas e of a n i na d e q u ate cli nical r es p o nse, t he s u bject’s pri mar y cli nical care t ea m will be 
c o ntacte d,  s o t hat t he s u bject ca n p urs u e treat me nt at t heir discreti o n. Re gar dless of resc u e 
t hera p y use d, s u bjects will c o nti n ue t o be f oll o we d u ntil t he e n d of t he st u d y. 
6. 5. 
U nsc he d ule d Visits  
Data c ollecte d fr o m s u bj ects w h o c o ntact t he st u d y tea m ( b y tele p h o ne, electr o nicall y, or i n-
pers o n) o utsi de of t he s c he d ule d visits (as a b o ve) will be ass ociate d wit h t h e ne xt sc he d ule d 
st u d y visit, as eac h st u d y visit is i nte n de d t o retr os pecti vel y c o ver t he ti me peri o d si nce t he last 
st u d y visit. 


 
P M T f or Se vere-C DI  
 
P a ge 2 8  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
6. 6. 
S u bject Wit h dr a w al  
S u bjects ma y wit h dr a w fr o m t he st u d y at a n y ti me wit h o ut i m pact t o t heir re g ul ar me dical care, 
b ut t he y will recei ve n o f urt her treat me nt wit h i n vesti gati o nal pr o d u ct . T he y ma y als o be 
disc o nti n ue d fr o m t he st u d y at t he discreti o n of t he I n v esti gat or f or lac k of a d here nce t o 
i nter ve nti o n or st u d y pr o ce d ures or visit sc he d ules, a d verse e ve nt s, or d u e t o ot her c o ncer ns. T he 
I n v esti gat or or t he S p o ns or ma y wit h dra w s u bjects w h o vi olate t he st u d y pla n, or t o pr otect t he 
s u bject f or r eas o ns of saf et y or f or a d mi nistrati ve reas o ns. It will be d oc u m e nte d w het her or n ot 
eac h s u bject c o m pletes t he cli nical st u d y.  T he tar get e d st u d y e nr oll me nt is 9 0 s u bjects 
ra n d o mize d; s u bjects w h o wit h dra wal after ra n d o mizati o n will n ot be re place d. 
6. 6. 1.  D at a C ollecti o n 
Data will be o btai ne d fr o m direct s u bject o bser v ati o n, re vie w of t he s u bject’s electr o nic m e dical 
rec or d, s c he d ule d a n d u nsc he d ule d f oll o w- u p visits ( w hic h ma y be i n- p ers o n or b y tel e p h o ne), as 
detaile d a b o ve. F or s u bjects w h o wit h dra w c o ns e nt t o partici pate i n t he st u d y, dat a c ollecte d u p 
u ntil t he ti me of wit h dra wal will  be ke pt, b ut n o f urt her data will be c ollect e d. 
6. 7. 
E arly Ter mi n ati o n Visits  
If t he s u bject deci des t o wit h dra w fr o m t he st u d y after ra n d o mizati o n, t he s u bject will be as ke d 
t o c o m plete all f oll o w-u p acti vities t hat w o ul d ha ve bee n p erf or m e d at t he n e xt sc he d ule d 
f oll o w- u p visit. 




 
P M T f or Se vere -C DI  
 
P a ge 3 0  of 4 4  
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
 
7.  St u d y E v al u ati o ns a n d Me as ure me nts  
7. 1. 
Me dic al Rec or d Revie w  
T he me dical r ec or d will be re vie w e d pri or t o e nr oll me nt, i n or der t o assess eli gi bilit y, as o utli ne d 
a b o ve. T he me di cal rec or d will be re vie we d at 3- d a y , 7- da y, 3 0- d a y, 9 0-d a y, a n d 1 8 0-da y 
f oll o w- u ps t o hel p ascertai n pri mar y a n d sec o n dar y o utc o mes, as well as a d verse e v e nts 
(Secti o ns 3. 2  a n d 9. 1. 3 ). HI P A A a ut h orizati o n will be o btai ne d wit h i nf or m e d c o nse nt. 
7. 2.  
P hysic al E x a mi n ati o n 
P h ysical e x a mi nati o n will i ncl u de o nl y of vital si g n meas ure me nts, as b el o w. 
7. 3. 
Vit al Si g ns  
Vital si g ns will be c hec k e d b y st u d y tea m pers o n n el d uri n g t he 6 0 mi n ute o bser vati o n peri o d 
after pr o d u ct a d mi nistrati o n. Para meters f or n otif yi n g t he cli nical care tea m of a b n or malities are 
o utli ne d i n t he st u d y i nter ve nti o n p hase secti o n a b o ve ( Secti o n 6. 2. 3 ). Vital si g ns will be 
c hec k e d w hile s u bjects are eit her sitti n g or l yi n g d o w n, as per t heir prefere nce.  
7. 4.  
L a b or at ory Ev al u ati o ns 
N o la b orat or y e val uati o ns will be perf or me d as a part of t his st u d y. L a b orat or y val u es will be 
c ollecte d fr o m re vie w of t he s u bject’s electr o nic me dical rec or d, i n or der t o ascert ai n o utc o me 
data  a n d a d v erse e ve nts, as descri be d a b o ve.  
7. 5. 
Pre g n a ncy Testi n g  
Uri ne p re g n a nc y testi n g usi n g a n F D A- cleare d test  will be perf or me d as a p art of t his st u d y. 
7. 6. 
Ot her Ev al u ati o ns, Me as ures  
S u bjects will be pr o vi de d wit h a diar y a n d t her m o meter t o kee p trac k of t h eir te m perat ure ( o n ce 
a da y), st o ol fr e q ue nc y, a n d a n y e mesis. T his diar y will be re vie we d wit h s u bjects at t heir 7- da y 
f oll o w- u p visit.  
 
F or t he e x pl orat or y ai m, st o ol micr o bi o me a nal ysis will be perf or me d o n st o ol sa m ples a n d peri -
rectal s w a bs. Li k e wise, i m m u ne p he n ot y pic a nal ysis usi n g fl o w c yt o metr y ma y b e perf or me d o n 
a s u bset of s u bjects usi n g w h ole bl o o d c ollecte d f or cli nical p ur p oses, w hi c h w o ul d ot her wise be 
discar de d.  St o ol s peci me ns will be o btai ne d b y pl aci n g fl oc ke d n yl o n s w a bs i n a vaila ble st o ol. 
P eri-rect al s wa bs will be o btai ne d if p ossi ble. Bl o o d will be c ollecte d fr o m resi d ual material 
a vaila ble i n E D T A (“ p ur ple t o p”) vac ut ai ner t u bes alrea d y c ollec te d i n t he cli nical la b orat or y. 
7. 7. 
Effic acy Ev al u ati o ns  
T he pri mar y o utc o me (ti me t o res ol uti o n of S/ S C/ F-C DI s y m pt o ms)  will be satisfie d w he n t he 
criteria liste d i n Secti o n 3. 2. 1  are met f or 7 2 h o urs or w he n t he s u bject is disc har ge d fr o m t he 
h os pital ( n ot t o h os pice or palliati ve care) . T h e crit eria will be assess e d via electr o nic me di cal 
rec or d re vie w as per S ecti o n  3. 2. 1 . 


 
P M T f or Se vere -C DI  
 
P a ge 3 1  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
7. 8. 
Ge netic Testi n g ( o nl y if a p plic a ble) 
N o h u ma n ge netic testi n g will be perf or me d. F or t he e x pl orat or y ai m, st o ol micr o bi o me a nal ysis 
will be perf or me d o n st o ol sa m ples a n d peri -rectal s wa bs o btai ne d as des cri be d i n Secti o n 7. 6 . 
T his will i n v ol ve se q ue nci n g of micr o bial n ucleic aci ds . T his will n ot i n v ol ve h u ma n D N A 
se q ue nci n g a n d t h us d oes n ot c o m prise ge netic testi n g. Li ke wise, p h e n ot y pi n g of i m m u ne 
res p o nse via fl o w c yt o metr y m a y be perf or m e d o n a s u bset of s u bjects, usi n g w h ole bl o o d 
c ollecte d f or cli nical p ur p oses t hat w o ul d ot her wise be discar d e d. T his will n ot i n v ol ve h u ma n 
D N A se q ue n ci n g a n d or ge n etic testi n g.  
7. 9. S afety Ev al u ati o ns 
7. 9. 1.  De vi ati o ns a n d E xc e pti o ns  
E xce pti o n  ( Pr os pecti ve acti o n): 
A n e xce pti o n  is defi ne d as a o ne-ti me, i nte nti o nal acti o n or pr ocess t hat de parts fr o m t he 
a p pr o ve d st u d y pr ot oc ol, i nte n de d f or o ne o cc urre nce. If t h e acti o n disr u pts t he st u d y pr o gress, 
s uc h t hat t he st u d y d esi g n or o utc o mes ma y be c o m pr o mise d, or t he acti o n c o m pr o mises t he 
safet y a n d/ or welfare of st u d y s u bjects, a d v a nce d oc u me nte d a p pr o v al fr o m t he Re g ulat or y 
S p o ns or a n d l ocal re g ulat or y re vie w c o m mittees, per i nstit uti o nal g ui deli nes, is re q uire d. 
A p pr o val fr o m t he Re g ul at or y S p o ns or m ust be recei ve d pri or t o s u b missi o n t o t he l ocal 
re g ulat or y re vie w c o m mittees. 
 
De vi ati o n  ( Retr os pecti ve acti o n): 
A devi ati o n is defi ne d as a o ne-ti me, u ni nte nti o nal acti o n or pr ocess t hat de parts fr o m t he 
a p pr o ve d st u d y pr ot oc ol, i n v ol vi n g o ne i nci de nt a n d i de ntifie d retr os pecti vel y. If t h e de viati o n 
disr u pts st u d y pr o gress, s uc h t hat t he st u d y d esi g n or o utc o mes ma y be c o m pr o mise d, or t he 
de viati o n c o m pr o mises t he safet y a n d/ or welfare of st u d y s u bjects, t he de viati o n m ust be 
re p orte d t o t he Re g ulat or y S p o ns or wit hi n 2 da ys of PI k n o wl e d ge a n d t o l ocal re g ulat or y re vie w 
c o m mittees per i nstit uti o nal g ui deli nes.  
Re p ort t he f oll o wi n g i nf or mati o n o n t he S p o ns or’s e x ce pti o n/ de viati o n f or m: 
•  Pr ot oc ol n u m ber 
•  S u bject n u m ber 
•  Descri pti o n of t he e x ce pti o n or de viati o n 
•  I m pact o n s u bject safet y 
•  I m pact o n data i nte grit y 
De viati o ns t hat are assesse d b y t h e PI t o n ot disr u pt t he st u d y pr o gress, s uc h as n ot affecti n g t h e 
st u d y desi g n or o utc o me, or c o m pr o misi n g t he s afet y a n d/ or welfare of st u d y s u bjects, s h o ul d be 
d oc u me nte d i n site rec or ds a n d c o ntai n d oc u me nt ati o n of t he PI’s assess m e nt. 
7. 9. 2.  S af et y P ar a met ers  
Safet y will be m o nit ore d i n se veral w a ys:  
•  
3 0- a n d 6 0- mi n ute  o bser vati o ns wit h vital si g n c h ec ks aft er i n vesti gati o nal pr o d uct 
a d mi nistrati o n . 
•  
F oll o w- u p dail y f or 3 d a ys  a n d at 7 da ys, 3 0 da ys, 9 0 da ys, a n d 1 8 0 da ys as o utli ne d i n t he 
sc he d ule of st u d y pr o ce dures  (Ta bl e 3 ). 
•  
E x a mi nati o n of safet y -rel ate d sec o n d ar y o utc o mes , i ncl u di n g: bact ere mia, m ortalit y, 
h os pital a d missi o n, c olect o m y or di verti n g ile ost o m y . 


 
P M T f or Se vere -C DI  
 
P a ge 3 2  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
8.  St atistic al Pl a n  
8. 1.  
Pri m ary E n d p oi nt 
T he pri mar y o utc o me is ti me t o res ol uti o n of s y m pt o ms ass ociate d wit h S/ S C/ F -C DI.  T h e 
pri mar y o utc o me will be satisfie d w he n t he s u bject is disc har ge d fr o m t he h os pital ( n ot t o 
h os pice or palliati ve care) or, w hile t he s u bject re mai ns h os pitalize d, w he n t he criteria liste d i n 
Secti o n 3. 2. 1  are satisfie d f or 7 2 h o urs. 
8. 2.  
Sec o n d ary E n d p oi nts 
Sec o n dar y e n d p oi nts are detaile d i n Secti o n 3. 2. 2 . Sec o n dar y e n d p oi nts will i ncl u de  all-ca us e 
m ortalit y ( 3 0- a n d 6 0- da ys f oll o wi n g e nr oll me nt ), colect o m y or di verti n g ile ost o m y wit hi n 3 0 
da ys after e nr oll me nt, cu m ulati ve da ys of h os pitalizat i o n fr o m e nr oll me nt u ntil 3 0 da ys aft er 
e nr oll me nt, cu m ulati ve d a ys i n i nte nsi ve care u nit fr o m e nr oll me nt u ntil 3 0 da ys after 
e nr oll me nt, b acter e mia fr o m e nr oll me nt u ntil 3 0 da ys after e nr oll me nt, rea d missi o n wit hi n 6 0 
da ys of disc har ge fr o m i n de x h os pitalizati o n . 
8. 3. E x pl or at ory E n d p oi nts 
E x pl orat or y e n d p oi nts will i ncl u de: ( 1) t h e bas eli ne g ut bacterial c o m m u nit y c o m p ositi o n a n d h ost 
i m m u ne  p he n ot y p e  ass o ciate d  wit h  S/ S C/F- C DI,  ( 2)  t he  c ha n ge  i n  g ut  bacteri al  c o m m u nit y 
c o m p ositi o n a n d h ost i m m u ne p he n ot y pe ass oci ate d wit h eac h of t he a b o v e treat me nt strat e gies, 
a n d ( 3) t h e r elati o ns hi p bet wee n b aseli ne g ut b acterial c o m m u nit y c o m p ositi o n, h ost i m m u ne 
p he n ot y p e,  a n d treat me nt o utc o me i n patie nts wit h S/ S C/ F -C DI . 
8. 4.  
S a m ple Size a n d P o wer Deter mi n ati o n  
Gi ve n t he a ntici pate d e nr oll me nt of 9 0 s u bjects, a n d t he pla n ne d pri mar y s ur vi val a nal ysis 
c o m pari n g ti me t o res ol uti o n of s y m pt o ms ass ociate d wit h S/ S C/ F -C DI acr oss F M T (a g gre gate) 
a n d n o-F M T gr o u ps, we a ntici pate t he f oll o wi n g statistical p o wer t o detect a re d ucti o n i n ti me t o 
res ol uti o n of s y m pt o ms i n t he F M T ( a g gre gate) gr o u p, base d o n a l o g-ra n k test: 


 
P M T f or Se vere -C DI  
 
P a ge 3 3  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
S/ S C/ F -C DI D ur ati o n 
wit h o ut F M T ( d a ys)  
Perce nt Ti me Re d ucti o n 
wit h F M T  
( D ur ati o n i n d a ys ) 
T y pe 1 Err or  
P o w er  
( b y b o otstr a p 
si m ul ati o n) 
2 
5 0 %  ( 1) 
0. 0 5  
0. 8 8  
0. 1  
0. 9 3  
0. 2  
0. 9 7  
4 
2 5 %  ( 3) 
0. 0 5  
0. 2 7  
0. 1  
0. 3 9  
0. 2  
0. 5 3  
5 0 %  ( 2) 
0. 0 5  
0. 8 8  
0. 1  
0. 9 3  
0. 2  
0. 9 7  
7 5 %  ( 1) 
0. 0 5  
0. 9 9  
0. 1  
0. 9 9  
0. 2  
0. 9 9  
7 
5 2 8 . 6%  ( 5) 
0. 0 5  
0. 3 5  
0. 1  
0. 4 7  
0. 2  
0. 6 1  
4 2. 9 %  ( 4) 
0. 0 5  
0. 7 3  
0. 1  
0. 8 2  
0. 2  
0. 9 0  
5 7 . 1%  ( 3) 
0. 0 5  
0. 9 6  
0. 1  
0. 9 8  
0. 2  
0. 9 9  
 
F or p has e II st u dies it is t y pical t o acce pt a t y pe 1 err or of greater t ha n 0. 0 5 ( Sc h oe nfel d 1 9 8 0; 
K ha n 2 0 1 2). F or t his p hase II st u d y, we will acce pt a differe nce b et wee n i nter ve nti o n gr o u ps t hat 
meets a t y p e I err or t hres h ol d of 0. 2. T heref ore, w e will h a ve 9 7 %  p o w er t o detect a re d ucti o n 
fr o m 4 t o 2 da ys ( 5 0 % r e d ucti o n) in t he F M T gr o u p if t he baseli ne d urati o n of se vere s y m pt o ms 
is bet wee n 4 da ys  a n d 9 0 % p o wer t o det ect a re d u cti o n fr o m 7 t o 4 da ys ( 4 2. 9 % re d ucti o n) i n t he 
F M T gr o u p if t he b aseli ne d urati o n of se v ere s y m pt o ms is bet wee n 7 da ys, b ot h base d o n a t y pe I 
err or rate of 2 0 %.  T he p o wer calc ulati o ns were perf or me d usi n g P A S S 1 6 ( P o wer A nal ysis a n d 
Sa m ple Size S oft ware ( 2 0 1 8). N C S S, L L C. Ka ys ville, Uta h, U S A, ncss.c o m/s oft ware/ pass.). 
 
8. 5. 
St atistic al Met h o ds 
8. 5. 1.  B aseli ne D at a  
Baseli ne a n d de m o gr a p hic c har acteristics, as well as vital si g ns , la b orat or y val ues, a n d ra di ol o gic 
st u d y res ults, will be s u m marize d b y sta n d ar d des cri pti ve statistics (i ncl u di n g mea n a n d sta n dar d 
de viati o n f or c o nti n u o us varia bles s uc h as a ge a n d sta n dar d perce nta ges f or cate g orical varia bl es 
s uc h as ge n der). C ollecte d varia bles will i ncl u de b ut n ot be li mite d t o: b o d y mass i n de x ( B MI), 
c o m or bi d me dical c o n diti o ns, use of i m m u n os u p pressi ve me dicati o ns, use of pr ot o n p u m p 
i n hi bit or ( P PI) or H 2 a nta g o nist me dicati o ns, use of c o nc urre nt n o n- C DI directe d a nti bi otics, 
h os pital le n gt h of sta y a n d le vel of care. Ti me b et wee n C DI dia g n osis a n d i nter ve nti o n will als o 
be assesse d . 


 
P M T f or Se vere -C DI  
 
P a ge 3 4  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
8. 5. 2.  Effic ac y A n al ysis 
A m o difie d i nte nti o n -t o-treat ( m-I TT) a n al ysis will be perf or m e d f or t he pri mar y o ut c o me of 
ti me t o C DI res ol uti o n (e n d p oi nt o utli ne d a b o ve). I n t he m-I T T a n al ysis, s u bjects w h o die 
f oll o wi n g r a n d o mizati o n b ut bef ore r ecei vi n g t heir first F M T will be e x cl u de d. A c o m peti n g 
ris ks s ur vi val m o del will be use d t o c o m pare t he F M T (a g gre gate) a n d n o- F M T gr o u ps. A p-
val ue ( o ne-si de d) of < 0. 2 will be c o nsi dere d si g nifica nt. 
8. 5. 3.  I nteri m A n al ysis 
N o i nteri m a nal ysis is pla n ne d. 
8. 5. 4.  S af et y A n al ysis 
All s u bjects e ntere d i nt o t he st u d y a n d ra n d o mize d will ha ve de taile d i nf or mati o n c ollecte d o n 
a d verse e v e nts starti n g at e nr oll me nt a n d f or t he d urati o n of f oll o w -u p, as descri be d else w here. 
T he pri mar y safet y e n d p oi nts of fre q ue n c y of A Es, S A Es, a n d A E SIs will be descri b e d.  
8. 5. 5.  E x pl or at or y A n al yses 
T o c haracterize ( 1) t he b aseli ne g ut bacterial c o m m u nit y c o m p ositi o n a n d h ost i m m u ne p he n ot y p e 
ass ociate d wit h S/ S C/ F -C DI , we will a p pl y 1 6 S ri b os o mal R N A (r R N A) ge n e se q ue nci n g t o i nitial 
( pre-F M T) st o ol s peci me ns, L u mi ne x bea d assa y (c yt o ki ne/ c he m o ki ne le vels) a n d fl o w c yt o m etric 
a nal ysis ( gra n ul o c yt e/ m o n o n uclear cell c o u nts) t o ser u m a n d bl o o d s peci me ns c ollecte d as part of 
r o uti ne cli nical care pri or t o F M T. T o c h aracteri ze ( 2) t he c ha n ge i n g ut bacterial c o m m u nit y 
c o m p ositi o n a n d h ost i m m u ne p he n ot y pe ass oci ate d wit h eac h  of t he a b o v e treat me nt strat e gies, 
we will a p pl y t he s a me assa ys t o p ost -F M T st o ol , peri-rectal, a n d s er u m/ bl o o d s peci me ns. T o 
deter mi ne ( 3) t h e  r elati o ns hi p  bet wee n  bas eli ne  g ut  b acteri al  c o m m u nit y  c o m p ositi o n,  h ost  
i m m u ne  p he n ot y pe,  a n d  treat me nt  o utc o me  i n  patie nts  wit h  S/ S C/ F -C DI ,  we  will  perf or m  
re gressi o n  m o deli n g  wit h  bacteri al  c o m m u nit y  c o m p ositi o n,  c yt o ki ne/c he m o ki ne  le vels,  a n d  
gr a n ul oc yte/ m o n o n uclear cell c o u nts as pre di ct or varia bles. 
8. 6. 
S u bject P o p ul ati o n(s) f or A n alysis  
F or t he pri mar y a nal ysis , a m o difie d i nte nti o n-t o-treat ( mI T T) p o p ulati o n will be use d, i n w hic h 
s u bjects w h o die f oll o wi n g r a n d o mizati o n b ut bef ore recei vi n g t heir first F M T will be e x cl u de d. 
Sec o n dar y i nte nti o n- t o-tr eat a n d per- pr ot oc ol a nal ys es will als o be p erf or me d. All ra n d o mize d 
s u bjects will be i ncl u de d i n t he latter a nal yses. 
9.  S af et y a n d A d verse E ve nts  
9. 1. 
Defi niti o ns  
9. 1. 1.  A d verse E ve nt  
A n a d vers e e ve nt ( A E) is a n y u nt o w ar d me dical o cc urre nce ass ociat e d wit h t he use of a dr u g i n 
h u ma ns, w het her or n ot c o nsi dere d dr u g relate d. I nterc urre nt ill nesses or i nj uries s h o ul d be 
re gar d e d as a d v erse e ve nts. 
 
A pre - e xisti n g c o n diti o n s h o ul d be rec or de d as a n a d verse e ve nt if t he fre q u e nc y, i nte nsit y or t he 
c haracter of t he c o n diti o n c ha n ges.  


 
P M T f or Se vere -C DI  
 
P a ge 3 5  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
9. 1. 2.  Seri o us A d verse E ve nt  
A d verse e ve nts ar e classi fie d as seri o us or n o n-seri o us. A seri o us a d vers e e ve nt ( S A E) is a n y A E 
t hat, i n t he vie w of eit her t he i n vesti gat or or t he s p o ns or, is: 
•  fatal 
•  life-t hreat e ni n g 
•  re q uires or pr ol o n gs h os pital sta y 
•  res ults i n persiste nt or si g nifica nt disa bilit y or i nca pacit y 
•  a c o n ge nital a n o m al y or birt h defect  
•  a n i m p orta nt me dical e v e nt  
 
I m p ort a nt me dical e v e nts are t h ose t hat ma y n ot b e i m me diatel y life t hreat e ni n g, b ut are cl earl y 
o f maj or cli nical si g nifica nce. T h e y ma y je o par di ze t he s u bject, a n d ma y re q uire i nter v e nti o n t o 
pre ve nt o ne of t he ot her s eri o us o utc o mes n ote d a b o ve. F or e x a m ple, dr u g o ver d ose or a b use, a 
seiz ure t hat di d n ot res ult i n i n- patie nt h os pitalizati o n, or i nte nsi ve treat me nt of br o nc h os pas m i n 
a n e mer ge nc y de p art me nt w o ul d t y picall y be c o nsi dere d ser i o us. 
9. 1. 3.  A d verse E ve nts of S peci al I nterest ( A E SI)  
Base d o n pri or p u blis he d e x perie nce wit h F M T- ass ociate d ris ks ( Ta bl e 1 ), we ha ve d efi ne d 
se veral a d vers e e ve nts of s pecial i nterest. 
 
I n t he i nitial, 6 0- mi n ute be dsi de o bser v ati o n peri o d f oll o wi n g a d mi nistrati o n of i n vesti gati o nal 
pr o d uct, s u bjects will be m o nit ore d wit h cl ose atte nti o n t o t he f oll o wi n g:  
•  aller gic r eacti o n (te m p er at ure, s ki n ras h, h eart rat e, or bl o o d press ure c h a n ge as alrea d y 
descri be d)  -- P M T - 0 0 1, 0 0 2, a n d 0 0 3 
•  se psis or s h oc k (te m perat ure, heart rate, or bl o o d press ure c ha n ge as alrea d y descri be d) 
– P M T - 0 0 1, 0 0 2, a n d 0 0 3 
•  b o wel i nj ur y (a b d o mi nal pai n c ha n ge as alrea d y d escri be d)  – P M T - 0 0 1, 0 0 2, a n d 0 0 3 
•  as pirati o n (res pir at or y r ate or o x y ge n sat urati o n c h a n ge as alrea d y d escri b e d)  – P M T -
0 0 2 a n d 0 0 3 o nl y 
 
I n t he s u bs e q ue nt, 7- d a y m o nit ori n g peri o d f oll o wi n g a d mi nistrati o n of i n v esti gati o nal pr o d u ct, 
s u bjects will be m o nit ore d wit h cl ose atte nti o n t o t he f oll o wi n g: 
•  d o n or- deri ve d i nfecti o n (te m perat ure or a b d o mi nal pai n c ha n ge as alrea d y descri be d)  – 
P M T - 0 0 1, 0 0 2, a n d 0 0 3 
•  w orse ni n g C DI (te m p erat ure, c ha n ge i n st o ol fre q u e nc y/ q ua ntit y or a b d o mi nal pai n, or 
e mesis as alrea d y descri b e d)  – P M T - 0 0 1, 0 0 2, a n d 0 0 3 
 
I n t he s u bs e q ue nt, 3 0-, 9 0-, a n d 1 8 0- da y m o nit ori n g peri o ds, s u bjects will be m o nit ore d wit h 
cl ose atte nti o n t o t he f oll o wi n g:  
•  tra ns mitte d i nfecti o n (te m perat ure or a b d o mi nal pai n c ha n ge as alrea d y d escri be d) – 
P M T - 0 0 1, 0 0 2, a n d 0 0 3 
•  rec urre nt C DI (t e m perat ure, c ha n ge i n st o ol fre q u e nc y/ q u a ntit y or a b d o mi nal pai n, or 
e mesis as alrea d y descri b e d)  – P M T - 0 0 1, 0 0 2, a n d 0 0 3 
•  meta b olic c ha n ges ( p ol y di psia,  p ol y uria, w ei g ht gai n, or wei g ht l oss) – P M T - 0 0 1, 0 0 2, 
a n d 0 0 3 


 
P M T f or Se vere -C DI  
 
P a ge 3 6  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
9. 1. 4.  E x pecte d A d verse E ve nts  
Base d o n o ur o w n e x peri e nce a n d t he p u blis he d literat ure ( Ta bl e 1 ), we e x pect t hat 
gastr oi ntesti nal s y m pt o ms (i ncl u di n g fe ver, as pirati o n, belc hi n g, bl oati n g, n a usea or v o miti n g, 
gastr o es o p ha geal refl u x, a b d o mi nal cra m ps, a b d o mi nal pai n, diarr hea, c o nsti pati o n) ma y be 
co m m o n p ost a d mi nistrati o n of all t hree  i n vesti gati o nal pr o d ucts, b ot h as a c o nse q ue nce of t he 
u n derl yi n g disease bei n g tr eate d, a n d p ot e ntiall y as a n a d vers e effect of t he a d mi nistere d 
pr o d uct. 
 
T o disti n g uis h a ca us al relati o ns hi p bet wee n t hese A Es a n d t he i n vesti gati o nal pr o d uct, we will 
set a t hres h ol d of > = 5 0 % i ncrease i n gastr oi ntesti nal s y m pt o m se v erit y  (e. g., n u m ber of st o ols or 
v ol u me of diarr hea; n u m ber of v o miti n g e pis o des or h o urs/ da y of na us ea) as c o m pare d t o 
s y m pt o m se verit y i n t he 4 8- h o ur peri o d s urr o u n di n g t he i nter v e nti o n. 
9. 2. 
Rec or di n g of A dverse E ve nts  
Safet y will be assesse d b y m o nit ori n g a n d rec or di n g p ote ntial a d v erse effects usi n g t he C o m m o n 
T o xicit y Criteria v ersi o n 5. 0 ( C T C A E V 5. 0) at eac h st u d y visit. Partici pa nts will be m o nit ore d 
b y me dical hist ories, p h ysical e x a mi nati o ns, a n d ot her st u dies. If C T C A E V 5. 0  gra di n g d oes n ot 
e xist f or a n a d verse e ve nt, t he se verit y of mil d, m o derate, s e vere, life-t hreat e ni n g, a n d deat h, 
c orres p o n di n g t o Gr a des 1- 5, will be use d w he n e v er p ossi ble. 
 
At eac h c o ntact wit h t he s u bject, t he i n vesti gat or will see k i nf or mati o n o n a d v erse e ve nts b y n o n -
directi ve q uesti o ni n g a n d, as a p pr o priat e, b y e x a mi nati o n. A d verse e v e nts ma y als o be detecte d 
w he n t he y ar e v ol u nteere d b y t he s u bject d uri n g t he scree ni n g pr ocess or bet wee n visits, or 
t hr o u g h p h ysical e x a mi nati o n, la b orat or y test, or ot her assess me nts. I nf or mati o n o n all a d verse 
e ve nts will be rec or de d i n t he s o urce d o c u me ntati o n. T o t he e xte nt p ossi ble, a d vers e e v e nts will 
be rec or de d as a dia g n osis a n d s y m pt o ms use d t o ma ke t he dia g n osis rec or de d wit hi n t he 
dia g n osis e v e nt. 
 
As m uc h as p ossi ble, eac h a d verse e ve nt or f oll o w- u p i nf or mati o n will be e val uate d t o 
deter mi ne:  
1.  Se verit y gra de ( C T C A E V 5. 0  Gra d e 1 - 5) 
2.  D urati o n (start a n d e n d d ates) 
3.  Relati o ns hi p t o t he st u d y treat me nt or pr o cess – [ Reas o na ble p ossi bilit y t hat A E is 
relate d: N o ( u nrelate d/ n ot s us pecte d) or Y es (a s us pecte d a d v erse reacti o n)]. If yes 
(s us pecte d) - is t he e ve nt p ossi bl y, pr o ba bl y or d efi nitel y relat e d t o t he i n vesti gati o nal 
treat me nt? 
4.  Acti o n ta ke n wit h res p ect t o st u d y or i n vesti gati o nal treat me nt or pr o cess ( n o ne, d ose 
a dj uste d, te m p oraril y i nterr u pte d, p er ma ne ntl y disc o nti n ue d, u n k n o w n, n ot 
a p plica ble)  
5.  W het her me dicati o n or t hera p y ta k e n ( n o c o n c o mita nt me dicati o n/ n o n- dr u g t hera p y, 
c o nc o mita nt me dicati o n/ n o n- dr u g t hera p y)  
6.  W het her t he e ve nt is seri o us 
 
O nce a n a d ver s e e v e nt is detecte d, it s h o ul d be f oll o we d u ntil its res ol uti o n or u ntil it is j u d ge d t o 
be per ma n e nt, a n d assess me nt s h o ul d be ma de at eac h visit ( or m ore fre q u e ntl y, if necessar y) of 


 
P M T f or Se vere -C DI  
 
P a ge 3 7  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
a n y c ha n ges i n se verit y, t he s us pecte d relati o ns hi p t o t he st u d y treat me nt, t he i nter ve nti o ns 
re q uire d t o treat it, a n d t he o utc o me. 
9. 3. 
Re p orti n g of A dverse Eve nts  a n d U n a ntici p ate d Pr o ble ms 
 
Re p orti n g peri o d  
A d verse e ve nts will be re p orte d fr o m t he ti me of i nf or me d c o ns e nt u ntil st u d y c o m pleti o n. 
 
I n vesti g at or re p orti n g: n otif yi n g t he st u d y s p o ns or 
T he s p o ns or m ust be n otifie d wit h i n 2 4 h o urs of lear ni n g of a n S A E o cc urre nce, re gar dless of 
s us pecte d ca usalit y (e. g., relati o ns hi p t o st u d y dr u g(s) or st u d y pr oce d ure or disease pr o gressi o n). 
 
At t he ti me of t he i nitial n otificati o n, t he f oll o wi n g i nf or m ati o n s h o ul d be pr o vi de d: 
•  St u d y i d e ntifier  
•  S u bject n u m ber 
•  A descri pti o n of t he e v e nt 
•  Date of o nset  
•  C urre nt stat us 
•  W het her st u d y treat me nt was 
disc o nti n ue d 
•  T he reas o n t he e ve nt is cl assifie d as 
seri o us 
•  I n v esti gat or assess ment of t he 
ass ociati o n bet wee n t he e ve nt a n d 
st u d y treat me nt 
 
F oll o w- u p i nf or mati o n o n S A Es s h o ul d be re p orte d w he n u p dates are a vail a ble, as a f oll o w- u p t o 
t he i nitial S A E re p ort, a n d s h o ul d i ncl u de b ot h t he f oll o w- u p n u m ber a n d re p ort date. Ne w 
i nf or matio n o n o n g oi n g s eri o us a d vers e e v e nts s h o ul d be pr o vi de d pr o m ptl y t o t he s p o ns or. T he 
f oll o w- u p i nf or mati o n s h o ul d descri be w h et her t h e e ve nt has res ol ve d or c o nti n ues, if t here are 
a n y c ha n ges i n assess me nt, if a n d h o w it was treat e d, a n d w het h er t he patie nt c o nti n ue d or 
wit h dre w fr o m st u d y partici pati o n. T he i n vesti gat or m ust f oll o w t he e ve nt t o res ol uti o n or u ntil 
t he e ve nt is dee me d a n d d oc u me nte d irre versi ble, w hic he ver is l o n ger. 
 
Rec urre nt e pis o des, c o m plicati o ns, or pr o gressi o n of t he i nitial S A E m us t be re p ort e d as t he 
f oll o w- u p t o t he ori gi n al e pis o de wit hi n 2 4 h o urs of t he i n vesti gat or recei vi n g t he f oll o w- u p 
i nf or mati o n. A n S A E c o nsi dere d c o m pletel y u nrelate d t o a pre vi o usl y re p orte d o ne s h o ul d be 
re p orte d se p ar atel y as a n e w e ve nt. 
 
I n a d diti o n, all u ne x pecte d fatal or life-t hreat e ni n g s us pecte d a d v erse reacti o ns will  be re p orte d 
t o t he F D A as s o o n as p ossi ble b ut i n n o case later t ha n 7 cale n d ar  da ys after t he s p o ns or’s i nitial 
recei pt of t h e i nf or mati o n. Ot her S A Es t hat are b ot h, u ne x pecte d a n d relat e d t o t he st u d y dr u gs 
(S U S A R ) will  be re p orte d t o t he F D A as s o o n as p ossi ble b ut n o later t ha n 1 5 cale n dar da ys after 
k n o wle d ge of t he e ve nt. 
 
I n vesti g at or Re p orti n g: L oc al Re p orti n g Re q uire me nts  
T he i n vesti gat or will re p ort A Es a n d S A Es t o his/ her I R B/ E C of rec or d a n d ot her l ocal 
re g ulat or y gr ou ps p er t he l ocal re q uir e me nts. 


 
P M T f or Se vere -C DI  
 
P a ge 3 8  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
9. 3. 1.  Pre g n a nc y  
Pre g n a nc y, i n a n d of itself, is n ot re gar d e d as a n A E u nless t here is s us pici o n t hat st u d y dr u g or 
pr ocess ma y h a ve i nterf ere d wit h t he effecti ve n ess of a c o ntrace pti ve  me di cati o n or met h o d. 
W he n a pre g na n c y has b ee n c o nfir me d i n a s u bject d uri n g mat er nal or p at er nal e x p os ure t o st u d y 
dr u g a n d/ or pr o cess, t he f oll o wi n g pr oce d ures s h o ul d be f oll o we d t o e ns ure s u bject safet y: 
 
Data o n fet al o utc o me will be  c ollecte d f or re g ulat or y re p orti n g a n d dr u g safet y e val uati o n. 
F oll o w- u p s h o ul d be c o n d ucte d f or eac h pre g na n c y t o deter mi ne o utc o me, i ncl u di n g s p o nta ne o us 
or v ol u ntar y ter mi nati o n, details of t he birt h, a n d t he prese n ce or a bse n ce of a n y birt h defects, 
c o n ge nital a b n or ma lities, or mater nal a n d/ or ne w b or n c o m plicati o ns. A cas e re p ort f or m will 
ca pt ure t hes e o utc o mes f or pre g na nt s u bjects, a n d t he s p o ns or will be n otifie d wit hi n 2 4 h o urs of 
rec or d e d a n a d vers e e ve nt relate d t o pre g n a nc y. 
9. 4.  
T o xicity M a n a ge m e nt, St o p pi n g R ules a n d St u dy Ter mi n ati o n 
E nr oll me nt a n d a d mi nistrati o n of t he st u d y pr o d u ct will be halte d pe n di n g re vie w b y t he st u d y 
staff a n d D ata Saf et y M o nit ori n g B o ar d  ( D S M B) if a n y s u bject e x perie n ces an A E t hat is  
assesse d as ( 1) seri o us (i. e., t hat res ults i n si g nifica nt s y m pt o ms pre ve nti n g n or mal dail y 
acti vities or re q uiri n g  h os pitalizati o n ), ( 2) u ne x pecte d , a n d ( 3) relat e d t o a d mi nistrati o n of t he 
st u d y pr o d uct. E nr oll me nt a n d a d mi nistrati o n of t he st u d y pr o d u ct will be h alte d pe n di n g re vie w 
b y t he st u d y staff a n d D ata Safet y M o nit ori n g B oar d ( D S M B) if a n y s u bject e x perie nces  a 
s us pected or pr o v e n i nfecti o n assesse d as relate d t o t he st u d y pr o d u ct. T he re vie w of t h ese 
a d verse e ve nts, a n d a n y decisi o n t o pre mat urel y st o p s u bject e nr oll me nt, will be deter mi ne d b y 
t he Me dical Dir ect or a n d D S M B.  
9. 5. 
Me dic al M o nit ori n g  
It is t he r es p o nsi bilit y of t he Pri nci pal I n vesti gat or t o o versee t he s afet y of t he st u d y at his/ her 
site. T his safet y m o nit ori n g will i ncl u de caref ul assess me nt a n d a p pr o priate re p orti n g of a d v erse 
e ve nts as n ote d a b o v e. 
9. 5. 1.  D at a a n d S af et y M o nit ori n g Pl a n 
A Dr u g Safet y M o nit ori n g Pla n has b ee n de v el o pe d base d o n ris k a n d is des cri be d i n a se p arat e 
d oc u me nt. T he m o nit ori n g pla n will  i ncl u de the f oll o wi n g  c o m p o ne nts: 
 
•  Pri nci pal I n v esti gat or m o nit ori n g 
•  T he S p o ns or Me dical Dir ect or 
•  Data Saf et y a n d M o nit ori n g B oar d ( D S M B)  
9. 5. 2.  D at a S af et y M o nit ori n g B o ar d 
A n i n de pe n de nt D S M B will perf or m e val u ati o ns of safet y dat a at s pecifie d i nter vals t hr o u g h o ut 
t he st u d y a n d ma k e r ec o m me n dati o ns t o t he S p o ns or re gar di n g f urt her c o n d uct of t he st u d y. T h e 
D S M B will e val uate s u bj ect saf et y as  s pecifi e d i n t he D S M B C harter. 


 
P M T f or Se vere -C DI  
 
P a ge 3 9  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
1 0.  S t u d y A d mi nistr ati o n, D at a H a n dli n g a n d Rec or d Kee pi n g 
1 0. 1.  C o nfi de nti ality  
I nf or mati o n a b o ut st u d y s u bjects will be ke pt c o nfi de ntial a n d ma na ge d acc or di n g t o t he 
re q uire me nts of t h e Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act of 1 9 9 6 ( HI P A A). 
T h ose re g ulati o ns re q uire a si g ne d s u bj ect a ut h orizati o n i nf or mi n g t he s u bject of t he f oll o wi n g: 
•  W hat pr otecte d healt h i nf or mati o n ( P HI) will be c ollecte d fr o m s u bjects i n t his st u d y  
•  W h o will ha ve access t o t hat i nf or mati o n a n d w h y 
•  W h o will use or discl ose t hat i nf or mati o n  
•  T he ri g hts of a r esearc h s u bject t o re v o ke t heir a ut h orizati o n f or use of t heir P HI. 
 
I n t he e ve nt t hat a s u bj ect re v o kes a ut h orizati o n t o c ollect or use P HI, t he i n vesti gat or, b y 
re g ulati o n, retai ns t he a bilit y t o use all i nf or mati o n c ollecte d pri or t o t he re v ocati o n of s u bject 
a ut h orizati o n. F or s u bjects t hat ha ve re v o k e d a ut h orizati o n t o c ollect or use P HI, atte m pts s h o ul d 
be ma de t o o btai n p er missi o n t o c ollect at least vital stat us (i.e. t hat t he s u bject is ali ve) at t he 
e nd of t heir sc h e d ule d st u d y peri o d. 
1 0. 2.  F ut ure Use of St ore d S peci m e ns a n d D at a  
St o ol a n d bl o o d s peci me ns c ollecte d as a b o ve ( Secti o n 7. 6 ) ma y be preser v e d i n fr oze n st ora ge f or 
f ut ure a n al ys es. T he d ata ge n erat e d fr o m t h ose s p eci me ns will o nl y be use d f or res earc h p ur p os es. 
It will n ot be s har e d wit h s u bjects or be use d t o direct treat me nt. 
1 0. 3.  D at a C ollecti o n a n d M a n a ge m e nt 
Case Re p ort F or ms ( C R Fs) will be c o m plete d, wit h  c o pies eit her pri nte d a n d st ore d i n bi n ders i n 
a sec ur e l ocati o n or s ec ur el y st or e d i n a n a p pr o v e d electr o nic s yste m t o w hi c h o nl y st u d y 
pers o n nel will ha ve access.  S u bject diaries will als o be c ollecte d a n d st ore d i n a sec ure l ocati o n. 
S u bjects will be assi g ne d a u ni q ue st u d y i de ntifi cati o n n u m ber , a n d P HI will be ke pt se paratel y 
wit h a master file st ore d o n a sec ur e, pass w or d - pr otecte d c o m p uter. Li n k a ge t o P HI will be 
st ore d u ntil st u d y a nal ysis a n d p u blicati o n c o m pleti o n, a n d t he n will be destr o ye d. 
 
E x pl orat or y micr o bi o me a nal ysis will be perf or me d  o n st o ol s peci me ns a n d e x pl orat or y i m m u ne 
res p o nse p he n ot y pi n g usi n g fl o w c yt o metr y will be  perf or me d usi n g a u ni q ue s t u d y i de ntifi cati o n 
n u m ber, wit h n o ass ociate d P HI. T h e e x pl orat or y a nal ysis of s u bject micr o bi o me c o m p ositi o n 
( will or will n ot) be s hare d wit h the s u bjects treati n g p h ysicia n.  
 
St o ol a n d bl o o d s peci me ns will be c o de d t o mai ntai n patie nt c o nfi de ntialit y a n d will be st ore d 
acc or di n g t o r e g ulati o ns. T he s u bject s pecific st o ol sa m ples be trac k e d wit h a master file li n ki n g 
P HI t o st u d y I D n u m bers, w hic h will be ke pt o n a sec ur e, p ass w or d -pr otect e d c o m p uter.  
1 0. 4.  R ec or ds Rete nti o n 
Data (el ectr o nic a n d pa p er) will be st ore d i n a sec ure l ocati o n u ntil st u d y a nal ysis a n d 
p u blicati o n c o m pleti o n, after w hic h a n y li n ka ge t o P HI will be  d estr o ye d. A n o n y mize d micr o bial 
n ucleic aci d se q ue nce dat a a n d ass oci ate d meta d ata will be u pl oa de d o n p u blic data bases (i. e., 
t he Nati o nal Ce nter f or Bi otec h n ol o g y I nf or mati o n’s Se q ue nce R ea d Arc hi ve) as re q uire d b y 
f u n di n g a ge ncies. 


 
P M T f or Se vere -C DI  
 
P a ge 4 0  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
1 1.  St u d y M o nit ori n g, A u diti n g, a n d I ns pecti n g  
1 1. 1.  St u dy M o nit ori n g Pl a n  
T his st u d y will be m o nit ore d acc or di n g t o t he dat a safet y m o nit ori n g pla n. T he i n vesti gat or will 
all ocate a d e q uate ti me f or s uc h m o nit ori n g acti vities. T he I n vesti gat or will als o e ns ure t hat t he 
m o nit or or ot her c o m plia nce or q ualit y ass ura nce re vie wer is gi ve n access t o all t he a b o ve n ote d 
st u d y-r elate d d oc u m e nts a n d st u d y r elate d facilities (e. g. p har mac y, dia g n ostic la b orat or y, etc.), 
a n d has a de q u ate s pace t o c o n d uct t he m o nit ori n g visit. 
1 1. 2.  D at a Q u ality Ass ur a nce  
D uri n g  m o nit ori n g visits,   t he m o nit or will  re vie w C R Fs  t o  e ns ure data acc urac y, 
c o m plete ness, a n d clarit y, i ncl u di n g la b orat or y re p orts a n d ot her s u bject rec or ds wit h t he 
sti p ulati o n t hat s u bject c o nfi de ntialit y will be stri ctl y mai ntai ne d i n acc or d a nce wit h l ocal a n d 
fe der al re g ulati o ns, i ncl u di n g HI P A A re q uire me nts. I nsta n ces of missi n g or u ni nterr u pti ble data 
will be res ol ve d i n c o or di nati o n wit h t he I n vesti gat or.  
1 1. 3.  A u diti n g a n d I ns pecti n g 
T he i n vesti gat or will per mit st u d y -relate d m o nit ori n g, a u dits, a n d i ns pecti o ns b y t he E C/I R B, t h e 
s p o ns or, g o v er n me nt r e g ulat or y b o dies, a n d U ni v ersit y c o m plia nce a n d q u alit y ass ura nce gr o u ps 
of all st u d y r elate d d oc u me nts (e. g. s o urce d oc u me nts, re g ulat or y d oc u m e nts, data c ollecti o n 
i nstr u me nts, st u d y d ata, etc.). T he i n vesti gat or s hall n otif y t he S p o ns or of all a u dits a n d 
i ns pecti o ns b y r e g ulat or y b o dies. T he i n vesti gat or will e ns ure t he ca pa bilit y f or i ns pecti o ns of 
a p plica ble st u d y-r elate d f acilities (e. g. p har m ac y, dia g n ostic la b orat or y, et c.). Partici pati o n as a n 
i n vesti gat or i n t his st u d y i m plies acce pta n ce of p ot e ntial i ns pecti o n b y g o v er n me nt re g ulator y 
a ut h orities a n d a p plica bl e U ni versit y c o m plia nce a n d q ualit y ass ura nce offices. 
1 2.  Et hic al C o nsi der ati o ns 
T his st u d y is t o be c o n d u cte d i n acc or da n ce wit h a p plica ble U S g o v er n me nt re g ulati o ns a n d 
i nter nati o nal sta n dar ds of G o o d Cli nical Practice, a n d a p plica ble i nstit uti o nal researc h p olicies 
a n d pr oce d ures. 
 
T his pr ot oc ol a n d a n y a m e n d me nts will be s u b mitte d t o a pr o perl y c o nstit ute d i n de pe n de nt 
Et hics C o m mittee ( E C) or I nstit uti o nal Re vie w B o ar d (I R B), i n a gree me nt wit h l ocal le gal 
prescri pti o ns, f or f or mal  a p pr o val of t he st u d y c o n d uct. T he decisi o n of t he E C/I R B c o ncer ni n g 
t he c o n d uct of t he st u d y will be ma de i n writi n g t o t he i n vesti gat or a n d a c o p y of t his decisi o n 
will be pr o vi de d t o t he s p o ns or bef or e c o m me nce me nt of t his st u d y. 
 
Pr ot oc ol m o dificati o ns, e x ce pt t h ose i nte n de d t o re d uce i m me diate ris k t o st u d y s u bjects, ma y b e 
ma de o nl y b y t h e U ni versit y of Pe n ns yl va nia a n d t he S p o ns or. A pr ot oc ol c ha n ge i nte n d e d t o 
eli mi nate a n a p pare nt i m me diate hazar d t o s u bjects ma y be i m ple me nt e d i m me diatel y, pr o vi d e d 
t he I R B/I E C is n otifie d wit hi n 5 da ys. 
 
A n y p er ma ne nt c ha n ge t o t he pr ot oc ol m ust be ha n dle d as a pr ot oc ol a me n d me nt. T he writte n 
a me n d me nt m ust be s u b mitte d t o t he I R B/I E C a n d t he i n vesti gat or m ust a wait a p pr o val bef ore 
i m ple me nti n g t he c ha n ges. T he S p o ns or will s u b mit pr ot oc ol a me n d me nts t o t he a p pr o priat e 
re g ulat or y a ut h orities f or a p pr o val. 


 
P M T f or Se vere -C DI  
 
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P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
1 2. 1.  Ris ks 
T he mai n ris ks of t his st u d y are r elate d t o a d mi nistrati o n  of t he i n vesti gati o nal pr o d uct. T he m ost 
se vere p ossi ble ris ks i ncl u de: aller gic reacti o n,  d o n or-deri ve d i nfecti o n , as pirati o n (f or u p per 
gastr oi ntesti nal  a d mi nistr ati o n), b o wel perf orati o n (f or l o wer gastr oi ntesti nal a d mi nistrati o n), 
a n d deat h. Ot her ris ks i ncl u de: na usea, v o miti n g, a b d o minal pai n, diarr h ea, flat ule nce, fe ver. 
Pr o d uct s pecific ris ks are descri be d i n Secti o n  9. 1. 4 . 
 
T he oretical  l o n g-t er m ris ks ma y i ncl u de: c ha n ges i n meta b olis m, wei g ht c h a n ges, de vel o p me nt 
of a ut oi m m u ne c o n diti o ns. 
 
Ot her ris ks i ncl u de l oss of pri vac y or c o nfi de ntialit y, as a res ult of st u d y staff i nteracti n g wit h 
s u bjects. 
 
T hese ris ks will be disc usse d wit h s u bjects d uri n g t he i nf or me d c o nse nt pr ocess. T he eli gi bilit y 
criteria will hel p miti gat e t hese ris ks (e. g., e x cl u din g s u bjects wit h ne utr o p e nia or b o wel 
perf or ati o n, a n d n ot per mitti n g s u bjects at ris k f or as pirati o n t o recei ve i n vesti gati o nal pr o d uct 
via u p per gastr oi ntesti nal  deli ver y). T o mi ni mize t he ris k of pri vac y a n d c o nfi de ntialit y l oss, t he 
mi ni m u m n u m ber of re q uire d st u d y staff will i nteract wit h s u bjects, a n d all c ollecte d data will be 
pr otecte d as a b o ve. 
1 2. 2.  Be nefits  
P ote ntial direct be nefits i ncl u de: c ure or i m pr o ve me nt of C DI s y m pt o ms m ore q uic kl y t h a n wit h 
sta n dar d of car e, re d u cti o n i n ris k of c o m plicati o ns of C DI ( deat h, nee d f or s ur ger y), re d ucti o n i n 
ris k of rec urre n ce of C DI, w hic h ha ve b ee n s u g geste d b y o bs er vati o nal st u dies t o date (Ta ble 1 ). 
In dir ect be n efits i nc l u de c o ntri b uti n g t o me dical k n o wle d ge a b o ut t he utilit y of F M T i n t his 
st u d y p o p ulati o n a n d t her ef ore h el pi n g p atie nts w h o ha ve t his disease i n t he f ut ure. 
1 2. 3.  Ris k Be nefit Assess m e nt  
Base d o n t h e ris ks a n d be nefits o utli ne a b o ve, t he be nefits of t his st u d y o ut wei g h t h e p ote ntial 
ris ks. T his is a patie nt p o p ulati o n wit h si g nifica nt ill ness at hi g h ris k f or c o m plicati o ns, a n d t he 
i n vesti gati o nal pr o d u cts are li kel y t o re d u ce t his ris k. W hile t here are p ote ntial a d verse o utc o m es 
ass ociate d wit h t his pr o d uct, pri or st u dies ha ve d e m o nstrate d t hat t he ris k of t he se occ urri n g is 
relati vel y l o w. 
1 2. 4.  I nf or m e d C o nse nt Pr ocess / HI P A A A ut h oriz ati o n 
I nf or me d c o ns e nt m ust be o btai ne d bef ore a n y of t he baseli ne pr o ce d ures are perf or me d. T h e 
c o nse nt pr ocess will occ ur i n t he setti n g of t he p ote ntial s u bject’s re g ularl y sc he d ule d cli nical 
care or b y tele p h o n e after referral fr o m t he p ote nti al s u bject’s cli nical care t ea m. Writte n 
i nf or me d c o nse nt will be o btai ne d w he ne v er p ossi ble. I n cas es w here C O VI D- 1 9 is olati o n stat us 
or visit or p olicies precl u de a n i n- pers o n c o nse nt pr ocess, ver bal c o ns e nt will be o btai ne d 
utilizi n g a wit nesse d c o nse nt. T his will be t h e n d oc u me nte d i n b ot h t he electr o nic healt h rec or d 
a n d t he data c ollecti o n s yste m. A n e x pla nati o n of t he trial a n d disc ussi o n of t he p ossi ble ris ks 
a n d disc o mf orts will be gi ve n b y t he I n vesti gat ors a n d/ or st u d y staff. O nl y t h ose p ote ntial 
s u bjects w h o f ulfill all eli gi bilit y criteria will be e ntere d i nt o t he trial. I nf or me d c o nse nt will ta ke 
place as a n o n g oi n g di al o g ue b et wee n t he I n vesti gat or/st u d y staff a n d s u bjects d uri n g t he e ntire 
d urati o n of t heir partici pati o n. P ote ntial s u bjects t hat are u n a ble t o rea d t he st u d y c o nse nt a n d/ or 


 
P M T f or Se vere -C DI  
 
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C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
d o n ot ha ve t he o p p ort u nit y t o ta ke h o me a n d re vi e w wit h fa mil y/frie n ds or d o n ot prese nt i n t he 
cli nic wit h a fa mil y m e m ber will ha ve t he c o nse nt rea d t o t he m b y a st u d y t ea m me m ber i n t he 
prese nce of a n o n- partial pers o n t hat will verif y t h e c o nse nt has b ee n rea d i n f ull t o t he patie nt. 
Pri vac y will be preser ve d b y mi ni mizi n g t he n u m ber of st u d y staff i n c o ntact wit h t he p ote ntial 
s u bject. C oerci o n will be a v oi de d b y clearl y stati n g t hat decli ni n g t o partici pate will n ot affect 
cli nical car e. T he i nf or me d c o nse nt a n d HI P A A a ut h orizati o n will be d oc u me nte d o n pa per, a n d 
c o m plete d pa per rec or ds will be sca n ne d f or di gital st ora ge o n sec ure u ni versit y ser v ers. 
1 3.  St u d y Fi n a nces  
1 3. 1.  F u n di n g S o urce  
Pr o gr a m s u p p ort fr o m Pe n n Me dici ne, De p art me nt of Me dici ne, a n d Ce nt ers f or Diseas e C o ntr ol 
a n d Pre ve nti o n ( C D C) U 5 4 C K 0 0 0 4 8 5. 
1 3. 2.  C o nflict of I nterest  
All U ni versit y of Pe n ns yl va nia I n vesti gat ors will f oll o w t he U ni versit y of Pe n ns yl va nia P olic y 
o n C o nflicts of I nterest R elate d t o Researc h . 
1 3. 3.  S u bject Sti pe n ds or P ay m e nts 
T here are n o s u bject pa y me nts or sti pe n ds. 
1 4.  P u blic ati o n Pl a n  
T he i n vesti gat or is res p o nsi ble f or a ut h ori n g a fi n al cli nical st u d y re p ort a n d s hari n g wit h  t he 
s p o ns or tea m. T he Cli nical St u d y Re p ort will be iss ue d wit hi n 1 2 m o nt hs of data l oc k a n d t he 
res ults s u m mar y will be p oste d t o cli nicaltrials. g o v. as re q uire d b y le gal a gree me nt, l ocal la w, or 
re g ulati o n. A ma n uscri pt will be pr o gresse d f or p u blicati o n i n t he scie ntific literat ure if t he 
res ults pr o vi de i m p orta nt scie ntific or me dical k n o wle d ge. T his st u d y will be p u blis he d b y t he 
pri nci pal i n vesti gat or, Dr. La ut e n bac h. 
1 5.  Ref ere nces  
 
A gra w al M, Ar o nia dis O C, Bra n dt LJ, K ell y C, Free ma n S, S ura wicz C, Br o ussar d E, St oll ma n 
N, Gi o va nelli A, S mit h B, Ye n E, Tri ve di A, H u b ble L, K a o D, B or o d y T, Fi nla ys o n S, Ra y A, 
S mit h R. T he L o n g- ter m Efficac y a n d Safet y of Fecal Micr o bi ota Tra ns pla nt f or Rec urre nt, 
Se vere, a n d C o m plicat e d Cl ostri di u m difficile I nfecti o n i n 1 4 6 El derl y I n di vi d uals. J Cli n 
Gastr oe nter ol. 2 0 1 6 M a y; 5 0( 5): 4 0 3 – 4 0 7. P MI D: 2 6 3 5 2 1 0 6 
 
Ar o nia dis O C, Br a n dt LJ, Gree n b er g A, B or o d y T, Kell y C R, Mell o w M, S ura wicz C, Ca gle L, 
Nes hatia n L, St oll ma n N, Gi o va nelli A, Ra y A, S mit h R. L o n g- t er m F oll o w- u p St u d y of Fecal 
Micr o bi ota Tra ns pla ntati o n f or Se ver e a n d/ or C o m plicate d Cl ostri di u m difficile I nfecti o n: A 
M ultice nter E x perie nce. J Cli n Gastr oe nter ol. 2 0 1 6 Ma y; 5 0( 5): 3 9 8 – 4 0 2. P MI D: 2 6 1 2 5 4 6 0 
 
B oja n o va D P, B or d e nstei n S R. Fecal Tra ns pla nts: W hat Is Bei n g Tra nsferre d? P L o S Bi ol. 2 0 1 6 
J ul; 1 4( 7):e 1 0 0 2 5 0 3. P M CI D: P M C 4 9 4 2 0 7 2 
 
Ca m mar ota G, I a nir o G, Gas barri ni A. Fecal micr o bi ota tra ns pla ntati o n f or t he treat me nt of 


 
P M T f or Se vere -C DI  
 
P a ge 4 3  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
Cl ostri di u m difficile i nfecti o n: a s yste matic re vie w. J Cli n Gastr oe nter ol. 2 0 1 4 Se p; 4 8( 8): 6 9 3 –
7 0 2. P MI D: 2 4 4 4 0 9 3 4 
 
Ca m mar ota G, Ia nir o G, Til g H, Rajilić -St oja n o vić M, K u m p P, Sa t o kari R, S o k ol H, Ar k kila P, 
Pi nt us C, Hart A, Se gal J, Al oi M, Mas ucci L, M oli nar o A, Scal daferri F, G as barri ni G, L o p ez-
Sa nr o ma n A, Li n k A, de Gr o ot P, de V os W M, H ö ge n a uer C, M alfert hei n er P, Mattila E, 
Mil osa vlje vić T, Nie u w d or p M, Sa n g ui netti M, Si mr e n M, Gas barri ni A, E ur o pea n F M T 
W or ki n g Gr o u p. E ur o p ea n c o nse ns us c o nfere n ce o n faecal micr o bi ota tra ns pla ntati o n i n cli nical 
practice. G ut. B MJ P u blis hi n g Gr o u p; 2 0 1 7 A pr; 6 6( 4): 5 6 9 – 5 8 0. P M CI D: P M C 5 5 2 9 9 7 2 
 
Fisc her M, Si pe B, C he n g Y- W, P hel ps E, R o gers N, Sa gi S, B o h m M, X u H, Kassa m Z. Fecal 
micr o bi ota tra ns pla nt i n se vere a n d se v ere -c o m plicate d Cl ostri di u m difficile: A pr o misi n g 
treat me nt a p pr o ac h. G ut Micr o bes. 2 0 1 7 Ma y 4; 8( 3): 2 8 9 – 3 0 2. P M CI D: P M C 5 4 7 9 3 9 3 
 
Fisc her M, Si pe B W, R o gers N A, C o o k G K, R o b b B W, V u p pala nc hi R, Re x D K. Faecal 
micr o bi ota tra ns pla ntati o n pl us selecte d use of v a nc o m yci n f or se v ere- c o m plicate d Cl ostri di u m 
difficile i nfecti o n: descri pti o n of a pr ot oc ol wit h hi g h s uccess rat e. Ali me nt P har mac ol T her. 
2 0 1 5 A u g; 4 2( 4): 4 7 0 – 4 7 6. P MI D: 2 6 0 9 6 3 2 0 
 
Ha milt o n MJ, Wei n gar de n A R, Sa d o ws k y MJ, K h or uts A. Sta n dar dize d fr o ze n pre parati o n f or 
tra ns pla ntati o n of fecal micr o bi ota f or rec urre nt Cl ostri di u m difficile i nfecti o n. A m J 
Gastr oe nter ol. A merica n C olle ge of Gastr oe nt er ol o g y; 2 0 1 2 Ma y; 1 0 7( 5): 7 6 1 – 7 6 7. P MI D: 
2 2 2 9 0 4 0 5 
 
Ka o D, R oac h B, Sil va M, Bec k P, Ri o u x K, Ka pla n G G, C ha n g H-J, C o war d S, G o o d ma n KJ, 
X u H, Ma dse n K, M as o n A, W o n g G K- S, J o vel J, Patters o n J, L o uie T. Effect of Oral Ca ps ule- 
vs C ol o n osc o p y- D eli vere d Fecal Micr o bi ota Tra ns pla ntati o n o n R ec urre nt Cl ostri di u m difficile 
I nfecti o n: A Ra n d o mize d Cli nical Trial. J A M A. A merica n Me di cal Ass ociati o n; 2 0 1 7 N o v 
2 8; 3 1 8( 2 0): 1 9 8 5 – 1 9 9 3. P M CI D: P M C 5 8 2 0 6 9 5 
 
Kell y BJ, Te bas P. Cli nical Practice a n d I nfrastr uct ure Re vie w of Fecal Micr o bi ota 
Tra ns pla ntati o n f or Cl ostri di u m difficile I nfecti o n. C hest. 2 0 1 8 J a n; 1 5 3( 1): 2 6 6 – 2 7 7. P M CI D: 
P M C 5 8 1 2 7 7 1 
 
Kell y C R, K h or uts A, Stale y C, Sa d o ws k y MJ, A b d M, Ala ni M, Ba k o w B, C urra n P, 
Mc Ke n ne y J, Tisc h A, Rei nert S E, Mac ha n J T, Bra n dt LJ. Effect of Fecal Micr o bi ota 
Tra ns pl a ntati o n o n Rec urre nce i n M ulti pl y Rec urre nt Cl ostri di u m difficile I nfecti o n: A 
Ra n d o mize d Trial. A n n I nter n Me d. 2 0 1 6 N o v 1; 1 6 5( 9): 6 0 9 – 6 1 6. P M CI D: P M C 5 9 0 9 8 2 0 
 
K ha n I, Sar k er S -J, Hac ks ha w A. S maller sa m ple sizes f or p hase II tri als base d o n e x act tests 
wi t h act ual err or r ates b y tra di n g- off t heir n o mi nal le vels of si g nifi ca nce a n d p o wer. Br J Ca ncer. 
2 0 1 2 N o v 2 0; 1 0 7( 1 1): 1 8 0 1 – 1 8 0 9. P M CI D: P M C 3 5 0 4 9 4 1 
 
Krajice k E, Fisc her M, Alle gr etti J R, Kell y C R. N uts a n d B olts of Fecal Mi cr o bi ota 
Tra ns pla ntati o n. Cli n Gastr oe nter ol He p at ol. 2 0 1 9 J a n; 1 7( 2): 3 4 5 – 3 5 2. P MI D: 3 0 2 6 8 5 6 4 
 


 
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P a ge 4 4  of 4 4  
 
 
P M T f or Se vere -C DI - Versi o n 1 0 . 0: 0 8 J u ne 2 0 2 1  
 
 
C o nfi de ntial a n d Pr o prietar y I nf or mati o n of t he Tr ustees of t he U ni versit y of P e n ns yl va nia  
Mc D o nal d L C, Ger di n g D N, J o h ns o n S, Ba k ke n J S, Carr oll K C, C offi n S E, D u b ber ke E R, 
Gare y K W, G o ul d C V, Kell y C, L o o V, S ha klee Sa m m o ns J, Sa n d ora TJ, Wilc o x M H. Cli nical 
Practice G ui deli nes f or Cl ostri di u m difficile I nfecti o n i n A d ults a n d C hil dre n: 2 0 1 7 U p date b y 
t he I nfecti o us Diseases S ociet y of A meri ca (I D S A) a n d S ociet y f or Healt hcare E pi de mi ol o g y of 
A merica ( S H E A). Cli n I nfect Dis. 2 0 1 8 Mar 1 9; 6 6( 7): 9 8 7 – 9 9 4. P M CI D: P M C 6 0 1 8 9 8 3 
 
Sc h oe nfel d D. Statistical c o nsi derati o ns f or pil ot st u dies. I nt J Ra diat O nc ol Bi ol P h ys. 1 9 8 0 
Mar; 6( 3): 3 7 1 – 3 7 4. P MI D: 7 3 9 0 9 1 4 
 
va n N o o d E, Vrieze A, Nie u w d or p M, F u e ntes S, Z oet e n dal E G, d e V os W M, Visser C E, 
K uij per EJ, Bartels ma n J F W M, Tijsse n J G P, S peel ma n P, Dij k graaf M G W, Keller JJ. D u o de nal 
i nf usi o n of d o n or feces f or rec urre nt Cl ostri di u m difficile. N E n gl J Me d. 2 0 1 3 J a n 
3 1; 3 6 8( 5): 4 0 7 – 4 1 5. P MI D: 2 3 3 2 3 8 6 7 
 
Wei n gar d e n A R, Ha milt o n MJ, Sa d o ws k y MJ, K h or uts A. Res ol uti o n of se vere Cl ostri di u m 
difficile i nfecti o n f oll o wi n g se q u e ntial fecal micr o bi ota tra ns pla ntati o n. J Cli n Gastr oe nter ol. 
2 0 1 3 Se p; 4 7( 8): 7 3 5 – 7 3 7. P M CI D: P M C 3 7 3 5 6 2 1 
 
Y o u n gster I, Ma h a ba m u n u ge J, S ystr o m H K, Sa u k J, K halili H, Le vi n J, Ka pla n J L, H o h ma n n 
E L. Oral, fr oze n fecal micr o bi ota tra ns pla nt ( F M T) c a ps ules f or rec urre nt Cl ostri di u m difficile 
i nfecti o n. B M C Me d. 2 0 1 6 Se p 9; 1 4( 1): 1 3 4. P M CI D: P M C 5 0 1 6 9 9 4 
 
Y o u n gster I, Sa u k J, Pi n dar C, Wils o n R G, Ka pla n J L, S mit h M B, Al m EJ, Ge vers D, R ussell 
G H, H o h ma n n E L. Fecal micr o bi ota tra ns pla nt f or rela psi n g Cl os tri di u m difficile i nfecti o n usi n g 
a fr oze n i n oc ul u m fr o m u nrelate d d o n ors: a ra n d o mize d, o pe n- la bel, c o ntr olle d pil ot st u d y. Cli n 
I nfect Dis. 2 0 1 4 J u n; 5 8( 1 1): 1 5 1 5 – 1 5 2 2. P M CI D: P M C 4 0 1 7 8 9 3 
 
Y o u n gster I, R ussell G H, Pi n dar C, Zi v- Bara n T, Sa u k J, H o h ma n n E L. Oral, ca ps ulize d, fr oze n 
fecal micr o bi ota tra ns pla ntati o n f or rela psi n g Cl ostri di u m difficile i nfecti o n. J A M A. 2 0 1 4 N o v 
5; 3 1 2( 1 7): 1 7 7 2 – 1 7 7 8. P MI D: 2 5 3 2 2 3 5 9