Topical Antibiotics in Chronic Rhinosinusitis
Phase: PHASE1
Conditions: Chronic Rhinosinusitis (Diagnosis)
Sponsor: Mayo Clinic

 
 
T o pic al A nti bi otics i n C hr o nic  
R hi n osi n usitis  
 
N C T 0 3 6 7 3 9 5 6 
 
A u g ust 2 6, 2 0 1 8  

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T o pic al A nti bi otics i n C hr o nic 
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T o pic al A nti bi otics i n C hr o nic R hi n osi n usitis  
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P R É CI S    
St u d y Title  
T o pical A nti bi otics i n C hr o nic R hi n osi n usitis 
O bjecti ve  
  
T he pri mar y o bjecti ve is t o s h o w t hat t he use of t o pical a nti bi otics i n t he treat me nt of 
c hr o nic r hi n osi n usitis d oes n ot lea d t o a nti bi otic resista nt or ga nis ms. T he sec o n dar y 
o bjecti ves ar e t o i n vesti gate t he effects of t o pical a nti bi otics o n patie nt s y m pt o ms as 
meas ure d b y t he v ali date d Si n o- Nasal O utc o mes Test ( S N O T - 2 2) a n d p h ysical e xa m 
e n d osc o pic fi n di n gs as d oc u me nte d b y L u n d- K e n ne d y e n d osc o pic s c ori n g s yste m. 
Desi g n a n d O utc o m es   
T his is a pr os pecti ve pil ot st u d y t o e val uate de vel o p me nt of a nti bi otic resista nce i n patie nts 
wit h c hr o nic r hi n osi n usiti s w h o are bei n g treate d wit h t o pical a nti bi otics. 
I nter ve nti o ns a n d D ur ati o n 
I nter ve nti o n i ncl u des 2 8 da ys of c ult ure directe d a nti bi otic t hera p y wit h o ne of t he f oll o wi n g 
f o ur t o pical a nti bi otics: T o bra m yci n, M u pir oci n, G e nta mici n or Le v ofl o x aci n  
   
S a m ple Size a n d P o p ul ati o n  
 
T here will be 2 0 p artici p a nts t otal i n t he st u d y a n d t he y will all recei ve t h e  i nter ve nti o n.  

T o pic al A nti bi otics i n C hr o nic R hi n osi n usitis  
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1  
S T U D Y O B J E C TI V E S  
1. 1  Pri m ar y O bjecti ve  
 
T he pri mar y o bjecti ve is t o descri be t he res ults of a nti bi otic resista nt or ga nis ms after t he use 
of t o pical a nti bi otics i n t he treat me nt of c hr o nic r hi n osi n usitis.  
       T he sec o n d ar y o bjecti ves are t o i n vesti gate 1) t he effects of t o pical a nti bi otics o n patie nt 
s y m pt o ms as meas ure d b y t he vali date d Si n o-Nas al O utc o mes Test ( S N O T - 2 2) a n d p h ysical 
e xa m e n d osc o pic fi n di n gs as d oc u me nte d b y L u n d- Ke n ne d y e n d osc o pic s c ori n g s yste m.  2) 
t he a d her e nce t o st u d y i nter ve nti o n  
2  
B A C K G R O U N D A N D R A TI O N A L E   
2. 1  B ac k gr o u n d o n C o n diti o n, Dise ase, or Ot her P ri m ar y St u d y F oc us 
T here is a p o p ulati o n of patie nts w h o ha ve c hr o ni c r hi n osi n usiti s t hat is refract or y t o 
ma xi mal me dical t hera p y i ncl u di n g treat me nt wit h sali ne a n d ster oi d nas al irri gati o ns as well 
as wit h oral ster oi ds a n d a nti bi otics.  
T he e vi de nce f or us e of t o pical a nti bi otics i n c urre nt literat ure is c o nflicti n g. T he fe w d o u bl e 
bli n d ra n d o mize d c o ntr ol st u dies cite d ha ve si g nifica nt li mitati o ns i ncl u di n g s mall sa m ple 
size, varia bl e i nter ve nti o n me dicati o ns a n d deli ver y met h o ds as well as varia ble o utc o mes 
meas ure d 1- 5. Ot her st u dies ha ve s h o w n t hat use of t o pical a nti bi otics i n C R S has tre n de d 
t o war d p ositi ve c ha n g e i n s y m pt o m sc ore a n d e n d osc o pic p h ysical e x a m fi n di n gs6. I n 
a d diti o n, t o pical a nti bi otics are c urre ntl y bei n g use d c o m m o nl y at t his i nstit uti o n f or patie nts 
wit h recalcitr a nt c hr o nic r hi n osi n usitis wit h g o o d cli nical a nec d ot al res ult. A well d esi g ne d 
st u d y is warrante d t o f urt her i n vesti gate t he utilit y of t o pical a nti bi otics i n c hr o nic 
r hi n osi n usitis.  
O ne c o ncer n wit h t o pical a nti bi otics li miti n g wi des prea d use is percei ve d i ncreas e d ris k of 
ca usi n g a nti bi otic resista nce . N o n -sta n d ar dize d d osa ge patter ns h as le d t o t he c o ncer n t hat 
patie nts are p ote ntiall y b ei n g treate d wit h s u bt hera p utic d osa ges. Ot hers p ost ulate t hat 
treat me nt wit h t o pical a nti bi otics a gai nst s usce pti ble bacteri a ma y  ha v e t he effect of i n d uci n g 
bi ofil m pr o d ucti o n fr o m resista nt bacteria 7. I n c o ntrast, a d v ocat es f or t o pical a nti bi otics 
e x pect t o pical deli ver y t o deli ver hi g h c o nce ntrati o ns of a nti bi otics  t o t he si n o nasal ca vit y 
w here t he y m a y pe netrat e a bacterial bi ofil m, a n d a v oi d t he syste mic effects of e nteral or 
pare nteral a nti bi otics 7. F urt her st u d y is warra nte d t o f urt her des cri be t he p ote ntial ass ociati o n 
of t o pical a nti bi otic treat me nt of t he si n o nasal ca vit y wit h a nti bi otic resista nce.  
O ur de part me nt has de vel o pe d i n c o nj u ncti o n wit h t he i nfecti o us disease d e part me nt a n d t he 
Ma y o p har mac y, a n eas y t o i m ple me nt set of t o pical a nti bi otics wit h  eas y t o use ca ps ules a n d  
set d osa ges f or us e b y o ur patie nts. T h is is a pil ot st u d y desi g ne d wit h  t he h y p ot hesis t hat 
t o pical a nti bi otics d o n ot ca use a nti bi otic resista n ce. I n a d diti o n, data will b e c ollecte d t o 
i n vesti gate s y m pt o m a n d p h ysical e xam o utc o mes i n patie nts  u n der g oi n g t o pical a nti bi otic 
t hera p y as sec o n dar y o utc o mes. T he st u d y will be  c o n d ucte d o n e xisti n g patie nts w h o w o ul d 
ot her wise recei ve treat m e nt wit h t o pical a nti bi otics as sta n dar d of care.  

T o pic al A nti bi otics i n C hr o nic R hi n osi n usitis  
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M ore o ver, ma n y of patie nts w h o ha ve recalcitra nt c hr o nic r hi n osi n usitis are i nfecte d b y t h e 
bacteria ps e u d o m o nas aer u gi n osa. T he use of t he fl u or o q ui n ol o ne class of a nti bi otics is a 
treat me nt of c h oice f or t his pat h o ge n. I n 2 0 0 8, t he U S F o o d a n d Dr u g A d mi nistrati o n iss ue d 
a “ blac k b o x ” a d visi n g ma n ufact urers t o w ar n pr o vi ders a n d patie nts of ris k i ncreas e d ris k of 
te n di nitis, te n d o n r u pt ure, peri p heral ne ur o pat h y. A well -st u die d, via ble alt er nati ve t o oral 
fl u or o q ui n ol o ne t hat w or ks well wit h o ut t he ass ociate d ris ks is warra nte d.  
Fi nall y, p o or pe netrati o n of oral a nti bi otics t o t he si n o nasal ca vit y d ue t o t he i nfecti o n bei n g 
wit hi n a s pace  ma y li mit t he efficac y of oral a nti bi otics as a treat me nt . I n c o ntrast use of 
t o pical a nti bi otics i n a patie nt w h o has pre vi o usl y u n der g o ne si n us s ur ger y, pr o vi des a 
p ote ntiall y m ore eff ecti v e deli ver y of m e dicati o n  t o t he i nfecte d s pace8. 
2. 2  St u d y R ati o n ale 
T he i nterve nti o n al re gi me n is as f oll o ws.  
Patie nt will u n der g o pre-i nter ve nti o n nasal s wa b fr o m t he affecte d si n us t h at will be se nt f or 
gra m stai n a n d  bacterial c ult ure a n d se nsiti vities.  
If pat h o ge n i de ntifie d i n t he bacterial c ult ure is pse u d o m o nas aer u gi n osa, t o pical t o bra m yci n 
or ge nta m yci n will be assi g ne d as first li ne a ge nt  p e n di n g c ult ure pr ofiles a n d c ost fact ors. If 
t he se nsiti vities s h o w resista nce t o b ot h t o bra m yci n a n d ge nta m yci n, t he n l e v ofl o xaci n will 
be prescri be d. 
If t he pat h o ge n i d e ntifie d i n t he bacterial c ult ure is ot her t ha n pse u d o m o nas aer u gi n osa, 
m u pir oci n will be prescri be d. If t he p at h o ge n s h o ws resista nce t o m u pir oci n, t he n t he patie nt 
will be prescri be d o n e of t he ot her t hree a nti bi otics will be prescri be d p e n di n g c ult ure 
pr ofiles a n d c ost f act ors 
T he patie nt will use t he t o pical a nti bi otic t wice a da y f or 2 8 da ys. T his will be acc o m plis he d 
b y first pr ocee di n g wit h t heir n or mal nasal ri nse re gi me n as prescri be d b y t heir p h ysicia n 
(t his ma y i ncl u de sali ne al o ne, or sali ne wit h b u des o ni de).  T wice p er da y, at t he e n d of eac h 
re gi me n, t he y perf or m o n e a d diti o nal nasal sali ne ri nse usi n g t he Neil Me d si n us ri nse b ottle 
i n t he ma n ner o utli ne d o n t he pac ka gi n g i nstr ucti o ns. H o we ver, wit h t his last a d diti o nal 
nasal sali ne ri nse, t he y will o pe n t heir a nti bi otic ca ps ule a n d dr o p t he c o nte nts i nt o t he ri nse 
b ottle pri or t o ri nsi n g. 
 
K n o w n a n d p ote nti al risks are as f oll o ws:  
P ote ntial ris ks  of nasal sali ne irri gati o n is sti n gi n g se nsati o n a n d b ur ni n g 
P ote ntial ris ks  of filli n g t he nasal sali ne irri gati o n ri nse b ottle wit h water t h at is t o o h ot is 
m uc osal b ur ns 
P ote ntial ris ks of t o pical a nti bi otic a d mi nistrati o n i ncl u de l ocal prurit is a n d i nfla m mati o n  
P ote ntial ris ks of  selecti o n a nti bi otic resista nt or ga nis ms.  
P ote ntial ris k f or heari n g l oss 
3  
S T U D Y D E SI G N  
T his is a pr os pecti ve, pil ot st u d y t o i n vesti gate t he prese n ce or a bse n ce of a nti bi otic resista nt 
or ga nis ms after tr eat me nt of c hr o nic r hi n osi n usitis wit h t o pical a nti bi otics. I n a d diti o n, 
t hera peutic eff ects of t he t o pical a nti bi o tics will be i n vesti gated via assess m e nt of  patie nt 
s y m pt o ms, a n d p hysical e xa m e n d osc o pic fi n di n gs. 

T o pic al A nti bi otics i n C hr o nic R hi n osi n usitis  
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T here will be 1  st u d y gr o u p wit h 2 0 patie nts.  
T he patie nts will first u n der g o pre-i nter ve nti o n assess me nt i n t he o ut patie nt setti n g. T his 
will occ ur i n t he De p art me nt of Ot or hi n olar y n g ol o g y o n t he 1 2 t h fl o or of t he G o n da b uil di n g 
i n R oc hester, M N wit h o ne of t he staff r hi n ol o gists. Patie nts will be selecte d t o partici pate if 
t he y ha ve acti ve m uc o p ur ule nce o n t heir e n d osc o pic e xa mi nati o n.  T he ass ess me nt will 
c o nsist of 1) o btai ni n g a nasal s wa b of m u c o p ur ul e nce fr o m t he affecte d si n us t o be se nt f or 
gra m stai n, c ult ure a n d s e nsiti vit y, 2) assess me nt of patie nt s y m pt o m se verit y sc ore as 
meas ure d b y t he s elf -a d mi nistere d Si n o -Nasal O utc o mes Test ( S N O T - 2 2) s ur ve y, a n d 3) 
assess me nt of patie nt p h ysical e xa m as e val uate d b y ri gi d nasal e n d osc o p y a n d d oc u me nte d 
i n L u n d- Ke n ne d y e n d osc o pic fi n di n gs f or m.  
T he st u d y i nter ve nti o n is t he a d mi nistrati o n of c ult ure directe d t o pical a nti bi otics o ver 2 8 
da ys. T hese a nti bi otics will prescri be d t o t he patie nt i n ca ps ule f or m as c o m p o u n de d b y t he 
Ma y o Cli nic p har mac y , or s uita ble lice nse d c o m p o u n di n g p har mac y.  On e ca ps ule will 
s u bse q ue ntl y be a d de d t o a nasal sali ne irri gati o n b ottle, a n d t he patie nt will a d mi nister t his 
irri gati o n t o hi m or herself i n t he us ual fas hi o n t wice per d a y. 
- 
T he d osa ges of t h e a nti bi otic ca ps ules were det er mi ne d b y t he Ma y o Cli nic p har mac y 
tea m wit h i n p ut fr o m i nfecti o us disease, bas e d u p o n a vaila ble p u blis he d data, a n d will be 
as f oll o ws, diss ol ve d i n a sta n dar d 2 4 0 m L sali ne irri gati o n ri nse 
o  M u pir oci n: 3 0 m g 
o  T o bra m yci n: 1 9 2 m g 
o  Ge nta mici n: 1 9 2 m g  
o  Le v ofl o xaci n: 2 5 0 m g 
After t he c o m pleti o n of t he st u d y i nter ve nti o n ( wit hi n 2 1 da ys), t he patie nt will u n der g o 
p ost-i nter ve nti o n assess me nt i n t he o ut patie nt setti n g, a gai n i n t he De part me nt of 
Ot or hi n olar y n g ol o g y wit h o ne of t he staff r hi n ol o gists. T he patie nt will a gai n be assesse d 
wit h 1) nasal s wa b fr o m t he aff ecte d si n us se nt f or gra m stai n, c ult ure a n d s e nsiti vit y 2) 
S N O T - 2 2 s y m pt o m sc ores a n d 3) L u n d- Ke n ne d y e n d osc o pic e x a m sc ores.  
 
4  
S E L E C TI O N A N D E N R O L L M E N T O F P A R TI CI P A N T S   
4. 1  I ncl usi o n Criteri a  
All partici pa nts i n t he st u d y m ust meet all of t he f oll o wi n g i ncl usi o n criteria t o partici pate 
i n t his st u d y. 
•  Male or fe m ale, bet w ee n 1 8 - 8 0 years ol d, dia g n os e d wit h c hr o nic r hi n osi n usitis 
w h o ha ve u n der g o ne pr e vi o us f u ncti o nal e n d osc o pic si n us s ur ger y i ncl u di n g at 
mi ni m u m ma xillar y a ntr ost o m y a n d a nteri or et h m oi dect o m y  
•  Acti ve m uc o p ur ule n ce o n e n d osc o pic e x a mi nati o n wit h c orres p o n di n g c ult ure 
de m o nstrati n g pat h o ge ni c bacterial gr o wt h  
•  C o m pleti o n of writte n i nf or me d c o nse nt 
•  N o pri or e nr oll me nt i nt o t his st u d y 
•  Refract or y t o ma xi mal me dical t hera p y  

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4. 2  E xcl usi o n Criteri a  
C a n di dates meeti n g a n y of t he f oll o wi n g e xcl usi o n criteria at baseli ne will be e x cl u de d 
fr o m st u d y partici pati o n.  
•  Patie nt has n ot ha d pri or e n d osc o pic si n us s ur ger y c o nsisti n g of at mi ni m u m 
bilateral ma xillar y a ntr ost o m y a n d a nteri or et h m oi dect o m y  
•  Patie nt is c urre ntl y bei n g treate d wit h oral a nti bi otics  
•  Patie nt has bee n treate d wit h oral or t o pical a nti bi otics wit hi n t he past 1 4 da ys 
•  Partici pati o n i n a n i n vesti gati o nal dr u g st u d y si m ulta ne o usl y wit h 
partici pati o n i n t his st u d y  
•  C o nc urre nt use of oral st er oi ds 
•  Aller g y t o T o bra m yci n, M u pir oci n, Ge nta mici n a n d Le v ofl o xaci n  
•  K n o w n t o c urr e ntl y be pre g na nt 
 
4. 3  St u d y E nr oll m e nt Pr oce d ures  
Garr et C h o b y, M D or st u d y staff will c o nse nt a n d e nr oll p ote ntial partici pa nts fr o m t he 
p o ol of pri nci pal a n d c o- i n vesti gat ors patie nts. 
 
Recr uit me nt will ta ke place i n G o n da 1 2 Ot or hi n olar y n g ol o g y de part me nt d uri n g t he 
patie nt's cli nical visit.  
 
T here will be n o scree ni n g l o g or ot her d oc u me ntati o n of reas o ns of i neli gi bilit y. 
 
T he c o nse nt a n d e nr oll me nt  pr ocess will occ ur i n a pri vate patie nt r o o m o n G o n da 1 2. 
W he n t he c o ns ulta nt has c o m plete d disc ussi n g differe nt treat me nt o pti o ns  wit h t he 
patie nt, a n d t he patie nt a n d t he p h ysicia n ha ve d eci de d o n t o p urs ue treat me nt wit h 
t o pical a nti bi otics, t he st u d y staff me m ber will i nf or m t he patie nt t hat he/s he meets t he 
criteria f or t his st u d y a n d descri be t he st u d y t o t he patie nt. T otal ti me of disc ussi o n is 
e x pecte d t o b e 1 0 mi n ute s. T he patie nt will be gi ve n a de q u ate ti me t o deci d e w het her or 
n ot t o partici pate i n t he st u d y.  
 
T he patie nt will be i nf or me d b y t he st u d y staff m e m ber of t he p ossi ble ris ks a n d be nefits 
of partici pati o n a n d st u d y staff me m ber will rei nf orce t hat t his is a decisi o n o nl y t he 
patie nt ca n ulti matel y ma ke. T he st u d y staff me m b er  will als o i nf or m t he patie nt t hat 
decli ni n g partici pati o n i n t he st u d y will i n n o wa y affect t he q ualit y or d urati o n of t heir 
care.  O nl y patie nts w h o ca n c o nse nt f or t he msel v es will be e nr olle d i n t his st u d y. 
 
If t he p ote ntial partici p a nt is a w o me n a ge 1 8- 5 0, t he Ma y o Cli nic “Pre -Pr o ce d ure 
Pre g na nc y Reas o na bl y E xcl u de d G ui de ( P R E G)” will be a d mi nistere d. If pre g na nc y is 
reas o na bl y e xcl u de d acc or di n g t o t he g ui de, t he patie nt will q ualif y f or e nr oll me nt. If t he 
patie nt is f o u n d t o be pre g na nt, s he will be e xcl u d e d fr o m t he st u d y.  
 

T o pic al A nti bi otics i n C hr o nic R hi n osi n usitis  
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5  
S T U D Y I N T E R V E N TI O N S    
5. 1  I nter ve nti o ns, A d mi nistr ati o n, a n d D ur ati o n  
T he pre-i nter ve nti o n assess me nt will occ ur d uri n g t he e nr oll me nt visit as part of r o uti ne 
cli nical car e. O nce t he r es ults of t he gra m stai n, c ult ure a n d se nsiti vities are k n o w n, t he 
patie nt will be prescri b e d t he a p pr o priat e t o pical a nti bi otic f or t he st u d y. T he y will be 
n otifie d of t he res ult of t he gra m stai n, c ult ure a n d se nsiti vities as well as t heir pe n di n g 
prescri pti o n via a p h o n e call or ot her electr o nic m ea ns, as per st u d y s u bject prefere nce. 
T he i nter ve nti o n will ta ke o ver t he c o urse of 2 8 d a ys as t he patie nt uses t h e me dicati o n as 
a n o ut patie nt. T her e will be o nl y o ne 2 8 da y d urati o n st u d y i nter ve nti o n a d mi nistere d 
after t he e nr oll me nt visit . T here will be n o m o dificati o ns t o t his st u d y i nter ve nti o n.  
 
5. 2  H a n dli n g of St u d y I nter ve nti o ns  
After c o m plet i o n of t he i nter ve nti o n, t he patie nt will prese nt f or p ost-i nter v e nti o n 
assess me nt i n t he De part me nt of Ot or hi n olar y n g ol o g y o n t he 1 2t h fl o or of t he G o n da 
b uil di n g i n R oc hester, M N wit h o ne of t he staff r hi n ol o gists. T his assess me nt will be 
e xactl y t he sa me as t he pre -i nter v e nti o n assess me nt. S pecificall y, t his assess me nt will 
c o nsist of 1) o btai ni n g a nasal s wa b of m u c o p ur ul e nce fr o m t he affecte d si n us t o be se nt 
f or gra m stai n, c ult ur e a n d se nsiti vit y, 2) assess me nt of patie nt s y m pt o m se verit y sc ore as 
me as ure d b y t he s elf- a d mi nistere d Si n o -Nasal O utc o mes Test ( S N O T - 2 2) s ur ve y, a n d 3) 
assess me nt of patie nt p h ysical e xa m as e val uate d b y ri gi d nasal e n d osc o p y a n d 
d oc u me nte d i n L u n d- K e n ne d y e n d osc o pic fi n di n gs f or m.  
5. 3  C o nc o mit a nt I nter ve nti o ns 
5. 3. 1  All o we d I nter v e n ti o ns 
A n y a d diti o nal me dicati o ns prescri be d t o t he p atie nt as part of t heir o n g oi n g t hera p y f or 
c hr o nic r hi n osi n usitis i ncl u di n g nasal sali ne irri gati o ns, ster oi d irri gati o ns, or t o pical 
s pra ys. 
5. 3. 2  Re q uire d I nter v e nti o ns  
N o ne 
5. 3. 3   Pr o hi bite d I nter v e nti o ns 
Patie nts will be e xcl u de d if t he y are prescri be d c o nc o mita nt oral ster oi ds  
5. 4  A d here nce Assess m e nt  
Defi niti o n of a d her e nce t o st u d y i nter ve nt i o n will st u d y s u bject attestati o n t hat t he y 
c o m plete d at least 4 8 / 5 6 d osa ges of nas al sali ne irri gati o n wit h t o pical a nti bi otic a n d 
prese ntati o n f or o n e p ost-i nter ve nti o n assess me nt. Patie nt will rec or d t o pical a nti bi otic 
use i n a dail y l o g. T his l o g will be use d b y t he i n vesti gat ors t o assess a d here nce.  T h ese 
a vaila ble e n d p oi nts will be ta ke n a n d i n c or p orate d i nt o a nal ysis.   
 

T o pic al A nti bi otics i n C hr o nic R hi n osi n usitis  
9 
6  
S T U D Y P R O C E D U R E S  
6. 1  
Sc he d ule of E v al u ati o ns  
 
Pre -I nter v e nti o n assess m e nt: t o be c o m plete d bef ore starti n g i nter ve nti o n 
•  Nasal s wa b: O btai n  s w a b fr o m affecte d si n us a n d se n d f or gra m stai n, c ult ure a n d 
se nsiti vity  
•  Patie nt s y m pt o m e val uati o n as assesse d b y S N O T - 2 2 s y m pt o m sc ores  
•  Patie nt e n d osc o pic p h ysical e xa m as assesse d b y  L u n d- Ke n ne d y e n d osc o pic e xa m 
sc ores.  D o c u me ntati o n p h ot os will als o be o btai ne d wit h t w o e n d osc o pic p h ot os 
per si de, o ne fr o m t he hea d of t he i nferi or t ur bi nat e i nt o t he nasal ca vit y a n d o ne 
fr o m t he hea d of t he mi d dle t ur bi nate t o war ds t he mi d dle meat us. 
 
P ost- I nter v e nti o n assess me nt: t o occ ur aft er t he c o m pleti o n of t he 2 8 da ys of i nter ve nti o n 
wit h t o pical a nti bi otics  
•  Nasal s wa b: O btai n s w a b fr o m affecte d si n us a n d se n d f or gra m stai n, c ult ure a n d 
se nsiti vit y  
•  Patie nt s y m pt o m e val uati o n as assesse d b y S N O T - 2 2 s y m pt o m sc ores  
•  Patie nt e n d osc o pic p h ysical e xa m as assesse d b y  L u n d- Ke n ne d y e n d osc o pic e xa m 
sc ores.  D o c u me ntati o n p h ot os will als o be o btai ne d wit h t w o e n d osc o pic p h ot os 
per si de, o ne fr o m t he hea d of t he i nferi or t ur bi nat e i nt o t he nasal ca vit y a n d o ne 
fr o m t he hea d of t he mi d dle t ur bi nate t o war ds t he mi d dle meat us. 
 
6. 2  Descri pti o n of E v al u ati o ns  
6. 2. 1  Scree ni n g E val u ati o n  
C o nse nti n g Pr oce d ure 
T here will be a si n gle i nf or me d c o nse nt f or m t hat descri bes b ot h t he scree ni n g a n d 
st u d y pr oce d ur es. 
 
Garr et C h o b y M D  or st u d y staff will c o nse nt p ote ntial partici pa nts fr o m t he p o ol of 
pri nci pal i n vesti gat or’s a n d c o-i n vesti gat ors’ patie nts. W he n t he staff m e m ber  has 
c o m plete d disc ussi n g t he i nter ve nti o n wit h t he patie nt, t he pr o vi der will i nf or m t he 
patie nt t hat he/s he meets t he crit eria f or t his st u d y. T otal ti me of disc ussi o n is 
e x pecte d t o b e 1 0 mi n utes. T he patie nt will be gi ve n ti me t o deci de if t he y w o ul d li ke 
t o partici pate i n t he st u d y.  
 
D oc u me ntati o n of si g ne d c o nse nt will be mai ntai ne d t hr o u g h m o nit ori n g b y Garr et 
C h o b y M D a n d st u d y staff a n d/ or E N T C o m mittee . T he d oc u me nt ati o n will be ke pt 
i n a sec ur e, l oc ke d ca bi n et i n t he De part me nt of Ot or hi n olar y n g ol o g y’s Researc h 
office  o nl y accessi ble t o PI a n d st u d y staff.  
 
 
Scree ni n g   
Scree ni n g will be bas e d o n pr oce d ures t hat are part of sta n dar d p atie nt care, a n d 
t heref or e, i nf or me d c o ns e nt will n ot be o btai ne d b y st u d y staff pri or t o scree ni n g 

T o pic al A nti bi otics i n C hr o nic R hi n osi n usitis  
1 0 
patie nts.  P ote ntial partici pa nts will c o me fr o m t he p o ol of patie nts dia g n ose d wit h 
c hr o nic r hi n osi n usiti s t hat t he pri nci pal i n vesti gat or a n d c o-i n v esti gat or c o ns ulta nts 
ha ve treate d.  
Scree ni n g e v al uati o n  f or patie nts i n b ot h gr o u ps i ncl u des:  
•  Patie nt De m o gra p hics  
•  Dia g n osis of c hr o nic r hi n osi n usitis 
•  Assess me nt of s y m pt o m sc ore wit h S N O T - 2 2 s ur ve y 
•  P h ysical E xa mi nati o n -I n v ol ves e xa mi nati o n of t h e patie nts bilateral nas al 
ca vities a n d para nas al si n uses wit h ri gi d e n d osc o p y 
•  Pre - Pr oce d ure Pre g n a nc y Reas o na bl y E xcl u de d G ui de ( P R E G) 
 
If t he p ote ntial partici p a nt is a w o me n a ge 1 8- 5 0, t he Ma y o Cli nic “Pre -Pr o ce d ure 
Pre g na nc y Reas o na bl y E xcl u de d G ui de ( P R E G)” will be a d mi nistere d. If pre g na nc y 
is reas o na bl y e x cl u de d acc or di n g t o t he g ui de, t he patie nt will q ualif y f or e nr oll me nt. 
If t he patie nt is f o u n d t o be pre g na nt, s h e will be e xcl u de d fr o m t he st u d y.  
 
T he st u d y staff will re vie w t hese tests fr o m t he patie nt’s me dical rec or ds t o deter mi ne 
eli gi bilit y.  Ti me pri or t o e nr oll me nt wit hi n w hic h t he scree ni n g tests a n d e v al uati o ns 
m ust be perf or me d is wit hi n 2 8 da ys of st u d y e nr oll me nt.  
6. 2. 2  E nr oll me nt a n d Baseli ne  
E nr oll me nt 
 
E nr oll me nt will be defi ne d as t he date all scree ni n g criteria are met a n d i n di vi d ual 
a grees t o p artici pate. T h ere will be a si n gle i nf or m e d c o nse nt f or m f or b ot h scree ni n g 
a n d st u d y pr oce d ures. E nr oll me nt a n d scree ni n g will be c o n d ucte d d uri n g t he sa me 
visit.  
T he criteri a use d f or i ncl usi o n a n d e xcl usi o n will be c ollecte d fr o m t he pati e nt o n t his 
date usi n g t he f oll o wi n g tests: 
•  me dicati o n rec o n ciliati o n  
•  Re vie w of me dical rec or d  
 
6. 2. 3  P ost- treat me nt assess me nt 
P ost- treat me nt assess me nt m ust be perf or me d aft er t he c o m pleti o n of t he i nter ve nti o n 
 
 
7  
S A F E T Y A S S E S S M E N T S   
7. 1  S pecific ati o n of S afet y P ar a meters  
 

T o pic al A nti bi otics i n C hr o nic R hi n osi n usitis  
1 1 
Safet y will be assesse d f or a d mi nistrati o n  of t o pical a nti bi otic via nasal irri gati o n t hat 
is t he s u bject of t he i nter ve nti o n u n der i n vesti gati o n. Assess me nt will i ncl u de details 
of a n y a d verse r eacti o n  at t he site of irri gati o n.  
7. 2  Met h o ds a n d Ti mi n g f or Assessi n g, Rec or di n g, a n d A n al yzi n g S afet y 
P ar a m eters  
Assess me nt  of a d verse r eacti o n  at t he p ost-i nter ve nti o n visit.  
7. 3  A d verse E ve nts  a n d Seri o us A d verse E ve nts  
A n  a d verse e v e nt  (A E ) is ge nerall y defi ne d as a n y  u nfa v ora bl e a n d u ni nte n de d 
dia g n osis, s y m pt o m, si g n (i ncl u di n g a n a b n or mal l a b orat or y fi n di n g), s y n dr o me or 
disease w hic h eit her occ urs d uri n g t he st u d y, ha vi n g bee n a bse nt at baseli n e, or if 
prese nt at bas eli ne, a p pears t o w orse n. A d verse e v e nts are t o b e rec or de d re gar dless 
of t heir relati o ns hi p t o t he st u d y i nter ve nti o n.    
 
A seri o us a d verse e v e nt (S A E ) is ge nerall y defi ne d as a n y u nt o w ar d me di cal 
occ urr e nce t hat res ults i n deat h, is life t hreat e ni n g, re q uires i n patie nt h os pit alizati o n 
or pr ol o n gati o n o f e xisti n g h os pitalizati o n, res ults i n persiste nt or si g nifica nt 
disa bilit y/i nca pacit y, or is a c o n ge nital a n o mal y . 
N o seri o us a d verse e v e nt o ut of c hara cter wit h nas al irri gati o ns  is e x pecte d.  
A d verse e ve nts ca pt ure d d uri n g i nter val cli nical visit are ca pt ure d as u ns oli cite d 
e ve nts, b ut if patie nt re p orts b y calli n g PI directl y usi n g n u m ber o n t he c o nse nt f or m 
it will be ca pt ure d as a s olicite d e ve nt. T he e v e nts will be rec or d e d as s uc h s o t hat 
t here are n o d o u ble c ollecti o n s yste ms.  
If t here ar e a n y a d v erse e ve nts or seri o us a d v erse e ve nts  re p ort e d b y t he patie nt t o t he 
c o-i n vesti gat ors at a n y p oi nt p ost-i nter ve nti o nal pr oce d ure t hr o u g h o ut t he st u d y, t he 
Pri nci pal I n v esti gat or will be n otifie d wit hi n 2 4 h o urs.  
7. 4  
Re p orti n g Pr oce d ures  
 
If t here ar e a n y a d v erse e ve nts or seri o us a d v erse e ve nts  re p ort e d b y t he patie nt t o t he 
c o-i n vesti gat ors at a n y p oi nt ( p ost-i nter ve nti o nal pr oce d ure) t hr o u g h o ut t h e st u d y, t he 
Pri nci pal I n v esti gat or wi ll be n otifie d wit hi n 2 4 h o urs. T he c o -i n v esti gat or will rec or d 
t he occ urre nce i n t he pati e nt’s researc h file wit hi n 2 4 h o urs of re p ort of t he i nci de nt. 
Decisi o n of rel ate d ness a n d se verit y will be ma de b y t he Pri nci ple I n vesti gat or. 
Details of t he a d v erse e v e nt will be mai ntai ne d i n t he Re p orta ble E ve nt Trac ki n g L o g 
f or t his st u d y. 
7. 5  
F oll o w- u p f or A d verse E ve nts  
A d verse e ve nts i n v ol vi n g i nfecti o n will be f oll o we d u p wit h a p pr o priate treat me nt 
i n v ol vi n g w o u n d c ult ures, br oa d s pectr u m a nti bi otics, a n d narr o w s pectr u m o nce t he 
s pecies is i de ntifie d. F oll o w u p will c o nti n ue as nee de d (ac ute d e bil itati n g e ve nt), 
u ntil res ol uti o n f or c hr o nic A D fr o m t he o cc urre n ce of a d v erse e ve nt. 

T o pic al A nti bi otics i n C hr o nic R hi n osi n usitis  
1 2 
8  
I N T E R V E N TI O N DI S C O N TI N U A TI O N  
  
 
Partici pa nts  ma y wit h dra w v ol u ntaril y fr o m partici pati o n i n t he st u d y at a n y ti me a n d f or 
a n y reas o n. Partici pa nts s h o ul d c o nti n ue t o be f oll o we d, wit h t heir per missi o n, after st u d y 
i nter ve nti o n has bee n a d mi nistere d .  
 
Re place me nt of p artici pa nts w h o disc o nti n ue earl y is all o we d. T he partici p a nts w h o are 
re place d will n ot be c o u nte d i n t he st u d y a n d re place me nt ca n occ ur if parti ci pa nts  d o n ot 
c o m plete t he at least 4 8 / 5 6 d osa ges of i nter v e nti o n wit h t o pical a nti bi otics .  
 
 It is vital t o c ollect saf et y data o n a n y s u bject dis c o nti n ue d d ue t o a n A E or S A E. I n a n y 
case, e v er y eff ort will  be ma de t o u n derta k e pr ot oc ol-s pecifie d safet y f oll o w- u p 
pr oce d ur es. If v ol u ntar y wit h dra wal occ urs, t he s u bject will  be as ke d t o c o nti nue 
sc he d ule d e v al uati o ns, c o m plete a n e n d-of -st u d y e val uati o n, a n d be gi v e n a p pr o priate 
care u n d er me di cal s u per visi o n u ntil t he s y m pt o ms of a n y A E res ol ve or t h e s u bject’s 
c o n diti o n bec o mes sta ble.  
9  
S T A TI S TI C A L C O N SI D E R A TI O N S     
9. 1  Ge ner al Desi g n Iss ues  
T his will be pr os pecti ve si n gle ar m pil ot st u d y. We pr o p ose e nr olli n g 4 0 patie nts i n t his 
st u d y.  
Meas ure of s uccess is p ost- treat me nt assess me nt wit h nasal s wa b se nt f or gra m stai n, 
c ult ure a n d se nsiti vit y. 
9. 2  S a m ple Size a n d R a n d o miz ati o n 
We pr o p ose e nr olli n g 4 0 patie nts i n t his st u d y. Si nce t his st u d y is a pil ot st u d y w here we 
ai m t o descri be t he r es ults a n d c ollect data f or f ut ure lar g er st u d y, sa m ple si ze calc ulati o n 
is n ot re q uire d. 
9. 3  I nteri m a n al yses a n d St o p pi n g R ules  
Safet y fi n di n gs t hat w o ul d te m p oraril y s us pe n d e nr oll me nt a n d/ or st u d y i nter ve nti o n u ntil 
a safet y r e vie w is c o n v e n e d ( eit her r o uti ne or a d h oc ) t o deter mi ne w het her t he st u d y 
s h o ul d c o nti n ue per pr ot oc ol, pr ocee d wit h ca uti o n, be f urt her i n v esti gate d, be 
disc o nti n ue d, or be m o difie d a n d t he n pr o cee d are as f oll o ws: 
  - N u m ber of S A Es o v erall 
  -N u m ber of o cc u rre nces of a partic ul ar t y pe of S A E 
  -Se vere A Es/reacti o ns  
  -I ncr ease d fre q u e nc y of e ve nts 
S uc h fi n di n gs are pr ese nt e d t o t he Data a n d Safet y M o nit ori n g B oar d ( D S M B) statisticia n 

T o pic al A nti bi otics i n C hr o nic R hi n osi n usitis  
1 3 
to re vie w t he e v e nts b y gr o u p t o deter mi ne w h et her t here are statistical as well as cli nical 
c o ncer ns. T h e statisticia n re p orts his fi n di n gs t o a cl ose d sessi o n of t he D S M B ( or t o t he 
Safet y Officer a n d/ or NI A.) T he fi n di n gs are use d t o deter mi ne w hat ste ps will be ta ke n.  
 
9. 4  O utc o m es  
9. 4. 1  Pri mar y O utc o me  
P ost treat me nt assess me nt of prese nce of a nti bi otic resista nt or ga nis m as ass esse d b y 
nasal s wa b se nt f or gra m stai n, c ult ure a n d se nsiti vit y  
9. 4. 2  Sec o n dar y o utc o mes   
T he sec o n d ar y o utc o mes are meas ure me nt of patie nt s y m pt o ms as meas ure d b y t he 
vali date d Si n o- Nasal O ut c o mes Test ( S N O T - 2 2)  a n d p h ysical e xa m e n d os c o pic fi n di n gs 
as d oc u me nte d b y L u n d- Ke n ne d y e n d os c o pic sc ori n g s yste m  
 
9. 5  D at a A n al yses 
St atistic al Met h o ds  
 
C o nti n u o us patie nt c haracters  will  be  s u m marize d  wit h  mea ns  a n d  sta n dar d  
de viati o ns f or feat ur es t hat are a p pr o xi mat el y n or mall y distri b ute d a n d wit h me dia ns, 
i nter q uartile ra n g es, a n d ra n ges ot her wise.  Cate g orical feat ures will be s u m marize d 
wit h fre q ue n c y c o u nts a n d perce nt a ges.   
 
Pri mar y e n d p oi nt: 
N u m ber a n d pr o p orti o n of patie nts w h o de vel o pe d a nti bi otic resista nce or ga nis m will 
be s u m marize d. 9 5 % c o nfi de nce i nter vals will be pr o vi de d f or t he pr o p orti o n. 
 
           Sec o n dar y e n d p oi nt:  
1)   S N O T - 2 2 s y m pt o m sc ores a n d L u n d- Ke n ne d y e n d osc o pic e xa m sc ore will be 
s u m marize d as mea n (sta n dar d de viati o n) a n d me dia n (ra n g e). 
  
   
 2). Defi niti o n of a d here n ce t o st u d y i nter ve nti o n will be t o c o m plete 2 5 of 2 8 da ys 
of t o pical a nti bi otics a n d atte n d t he pre- i nter ve nti o n / e nr oll me nt visit as well as t he 
p ost-i nter ve nti o n assess me nt visit. N u m ber a n d pr o p orti o n of patie nts wit h 
a d here n ce will be re p orte d.  
3) A u di o metric data will be s u m marize d as a mea n (sta n dar d de viati o n) a n d me dia n 
(ra n ge) 
 

T o pic al A nti bi otics i n C hr o nic R hi n osi n usitis  
1 4 
1 0  
D A T A C O L L E C TI O N A N D Q U A LI T Y A S S U R A N C E  
1 0. 1  D at a C ollecti o n F or ms 
Inf o r mati o n will be c ollecte d o n Case Re p ort F or ms ( C R Fs) b y st u d y staff.  Partici pa nt 
C R Fs will be ke pt i n a l oc ke d ca bi net i n t he D e p art me nt of Ot or hi n olar y n g ol o g y a n d o nl y 
st u d y staff will ha ve access t o t his ca bi net t o mai ntai n c o nfi de ntialit y of partici pa nt 
rec or ds.  
 
Data Ma na g e me nt  
All data is c hec k e d f or c o m plete ness a n d f or acc urac y o n dat a ra n g es.   
Data c ollecti o n f or ms will be or ga nize d i n t he f oll o wi n g cate g ories: 
  - E nr oll me nt / Pre-i nter ve nti o n assess me nt 
  - P ost-i nter ve nti o n assess me nt 
            Data will be c ollecte d a n d st ore d usi n g e x cel file.  
 
1 0. 2  Q u alit y Ass ur a nce  
1 0. 3. 1  
Trai ni n g 
C o -i n vesti gat ors will be briefe d o n t he st u d y pri m ar y a n d sec o n dar y o bjecti ves, t he 
st u d y desi g n a n d all i nf or mati o n i n t his pr ot oc ol will be re vie we d i n pers o n b y t he 
Pri nci pal I n v esti gat or .  
1 0. 3. 2  Q ualit y C o ntr ol C o m mittee  
E N T  Resear c h C o m mittee  is t he st u d y c o ntr ol c o m mittee. Jeffre y J a n us, M D is C hair 
of t his C o m mittee.  
1 0. 3. 3  Pr ot oc ol De viati o ns 
Pr ot oc ol de viati o ns will be ca pt ure d b y t he PI or st u d y staff at t he ti me of o cc urre nce, 
d uri n g s ur ger y or d uri n g f oll o w u p. I nf or mati o n o n de viati o n will be d oc u me nte d. 
T he st u d y will o nl y use data t hat is c o here nt wit h pr ot o c ol. 
1 1  
P A R TI CI P A N T  RI G H T S A N D C O N FI D E N TI A LI T Y   
1 1. 1  I nstit uti o n al Re vie w B o ar d (I R B) Re vie w 
T his pr ot oc ol a n d t he i nf or me d c o nse nt d oc u m e nt a n d a n y s u bse q ue nt m o dificati o ns will 
be re vie w e d a n d a p pr o ve d b y t he I R B.    
1 1. 2  I nf or m e d C o nse nt F or m 
A si g ne d c o nse nt f or m will be o btai ne d fr o m eac h  partici pa nt.   Partici pa nts w h o  ca n n ot 
c o nse nt f or t he msel v es will n ot be e nr olle d i n t his st u d y. T he c o nse nt f or m will descri be 
t he p ur p ose of t he st u d y, t he pr oce d ures t o be f oll o we d, a n d t he ris ks a n d be nefits of 
partici pati o n . A c o p y will be gi ve n t o eac h p artici pa nt a n d t his fact will be d oc u me nte d i n 

T o pic al A nti bi otics i n C hr o nic R hi n osi n usitis  
1 5 
t he partici pa nt’s r ec or d.  
1 1. 3  P artici p a nt C o nfi de nti alit y  
All rec or ds will be ke pt i n a l oc ke d file ca bi net.  All c o m p uter e ntr y a n d n et w or ki n g 
pr o gra ms will be d o ne b y eit her t he Pri nci pal I n v esti gat or or St u d y Staff usi n g sec ure 
l o gi n i nf or mati o n o nl y. Inf or mati o n will n ot be release d wit h o ut writte n per missi o n of t he 
partici pa nt, e xce pt as necessar y f or m o nit ori n g b y I R B, t he F D A, O H R P . 
1 1. 4  St u d y Disc o nti n u ati o n  
T he st u d y ma y be disc o nti n ue d at a n y ti me b y t he I R B, t he NI A, t he O H R P, t he F D A, or 
ot her g o ver n me nt a ge nci es as part of t h eir d uties t o e ns ure t hat researc h partici pa nts are 
pr otecte d.  
1 2  
P U B LI C A TI O N O F R E S E A R C H FI N DI N G S  
P u blicati o n of t he res ults of t his trial will be g o ve r ne d b y t he p olicies a n d pr oce d ures 
de vel o pe d b y t he E N T R esear c h C o m mittee.  A n y prese ntati o n, a bstract, or ma n uscri pt 
wi ll be ma de a vaila ble f or re vie w t o t he m b y PI pri or t o s u b missi o n . 
 
 

T o pic al A nti bi otics i n C hr o nic R hi n osi n usitis  
1 6 
 
1 3  
 
Refere nces  
 
1.   
Wei J L, S y kes KJ, J o h ns o n P, He J, Ma y o M S. Safet y a n d efficac y of o n ce-dail y nasal 
irri gati o n f or t he treat me nt of pe diatric c hr o nic r hi n osi n usitis. L ary n g osc o pe. Se p 
2 0 1 1; 1 2 1( 9): 1 9 8 9- 2 0 0 0. 
2.  
Jer vis- Bar d y J, B oase S, Psaltis A, F ore ma n A, W or mal d PJ. A ra n d o mize d trial of 
m u pir oci n si n o nasal ri nses vers us sali ne i n s ur gicall y recal citra nt sta p h yl o c occal c hr o nic 
r hi n osi n usitis. L ary n g osc o pe. Oct 2 0 1 2; 1 2 2( 1 0): 2 1 4 8- 2 1 5 3. 
3.  
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