Randomized Controlled Trial Comparing Endoscopic Balloon Dilation Versus Endoscopic Stricturotomy for Short Strictures (< 3 cm) Related to Crohn's Disease (the BEST-CD Trial)
Phase: NA
Conditions: Crohn Disease
Sponsor: Asian Institute of Gastroenterology, India

Study No: IBD-001                              Version No: 01                      Date: 
09-07-2022
Clinical study protocol 
Protocol title:  “Randomized controlled trial comparing endoscopic balloon dila-
tion versus endoscopic stricturotomy for short strictures (< 3 cm) related to 
Crohn’s disease (the BEST-CD trial)
Primary Investigator.”
Dr. PARTHA PAL
Asian Institute of Gastroenterology 
6-3-331, Somajiguda, Hyderabad, 5000082
Study description 
Brief Summary 
Crohn’s disease (CD) related strictures can be treated endoscopically by endoscopic 
balloon dilation (EBD) or endoscopic stricturotomy (EST). EBD is  is the established 
endoscopic treatment for short strictures in Crohn's disease. However, roughly half 
had recurrent symptoms and two third require surgery after EBD. ES have been used 
initially for endoscopic treatment of patients for whom EBD was unsuccessful. Sub-
sequently it was shown that ES is a better modality for treating CD related strictures 
(specially short and anastomotic strictures) than EBD lowering the risk of future 
surgery and procedure related perforation albeit with an increased risk of bleeding. ES 
was shown to be non-inferior to re-do surgery in chronic pouch anastomotic sinus in 
ulcerative colitis (UC) and ileocolic anastomotic strictures in CD thus reducing surgi-
cal morbidity. However, these two modalities have not been compared in a random-
ized controlled manner. We aimed to compare the two endoscopic treatments with re-
gard to clinical success, need for surgery or additional endoscopic procedure and safe-

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ty in patients with CD who have short (<3 cm), predominantly fibrotic stenosis ex-
cluding those in the small bowel not accessible by endoscope/colonoscopy. 
Detailed description 
Study design: Single centre, open-label, randomized trial to be done in Asian Insti-
tute of Gastroenterology, India 
Study population: All eligible consecutive patients with CD who developed DE-
nova or anastomotic strictures will be included. 
Study settings:
The proposed study would be conducted in a high volume tertiary GI centre (Asian 
Institute of Gastroenterology) performing nearly more than 200 EBD/ES procedures 
per year with an well established inflammatory bowel disease (IBD) registry with 
more than 7000 IBD patients under follow up.
The study will be conducted after approval by the institutional ethics committee. Writ-
ten informed consent would be taken from each participants and the study would con-
form to the 1975 Declaration of Helsinki ethical guidelines.
Data collection:  A survey administration software (google forms) would be used to 
collect the participant data (age, sex, ethnicity, clinical features, smoking status, de-
tails of CD diagnosis, disease phenotype, extra intestinal manifestations, family histo-
ry, history of intestinal resection, details of stricture diagnosis, details of stricture: de-
gree, number, location, radiological finding: concurrent abscess, fistula, enhancement; 
Condition or disease 
Intervention or treatment 
Crohn’s disease 
Intervention: Endoscopic balloon dilation 
Intervention: Endoscopic stricturotomy 

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drug history for CD, procedural details: technical success, symptomatic improvement, 
endoscopic improvement, stricture related emergency visit or hospitalization, compli-
cations, subsequent need for additional endoscopic procedures or surgery upto a fol-
low up of 1 year).  Follow-up details would be collected via physical visit or tele-
phonic communication.
Technique and instruments:  EBD procedures will be performed with wire guided 
CRE pneumatic balloon (controlled radial expansion balloon, Boston scientific, Marl-
borough, MA, USA 0of various sizes based on tightness of the stricture (10-12 mm, 
12-15 mm, 15-18 mm, 18-20 mm) with graded dilation with inflation pressures vary-
ing from 3-8 ATM pressure. Balloon was inflated for at least 2 minutes and slowly 
deflated. For mild ooze post EBD, balloon tamponade will also done with the same 
balloon. A maximum of two sessions of dilation will be allowed with a minimum in-
terval of 15-30 days between them. Additional EBD sessions would be considered as 
additional endoscopic procedure for the purpose of the study. 
Endoscopic stricturotomy would be done using a needle knife/insulted tip (IT) knife 
with the following electrocautery settings : Endocut Q (effect 3, cut duration 1, cut 
interval 3) as per by global IIBD group consensus. 
Definitions: Technical success for EBD was defined as ability to perform the EBD 
procedure. Scope passage after EBD/stricturotomy was assessed as a separate out-
come which was defined as passage of endoscope through the area where EBD/ES 
was performed. This included colonoscopy for colonic/pouch strictures, endoscope 
for upper GI and duodenal strictures and an endoscope: motorized spiral or single bal-
loon enteroscopy for small bowel strictures except those in terminal ileum. Clinical 

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success in EBD/ES was defined as clinical improvement in symptoms (pain/ intesti-
nal, gastric outlet or colonic obstruction symptoms) after the procedure. Sustained 
clinical success was defined as absence of obstructive symptoms at 1 year follow up. 
Major adverse events were defined as perforation, bleeding requiring transfusion or 
any procedure related prolongation of hospitalization period or an endoscopic, radio 
logic or surgical intervention. Minor adverse events were bleeding not requiring blood 
transfusion, post procedural pain and any other self limiting complication (e.g., sore 
throat after spiral enteroscopy) which does not warrant prolongation of hospital stay. 
Adverse events will be recorded for all the patients; events were considered associat-
ed to be with the procedure when a causal association was possible, probable, or defi-
nite. Recurrence of symptoms would be defined as re-emergence of symptoms for 
which the procedure was initially performed. 
Sample size
Based on previous retrospective study, symptomatic improvement with EST and EBD 
(9.5% and 33.5% respectively, the estimated sample size is total 90 (45 in each group) 
keeping type 1 error as 0.05 and power as 80%. 
Randomization
Patients will be randomly assigned (1:1) to receive either EBD (EBD group) or EST 
(EST group) using a digital en-block randomization system (block size of four).
Data analysis
Statistical analysis:  Statistical analysis would be done by using statistical package for 
social sciences (SPSS, IBM, NY, USA). Chi-square/Fisher's exact test was used to 

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compare categorical variables and Mann-Whitney test would used to compare contin-
uous variables between the two groups.P-value <0.05 would be considered statistical-
ly significant
Timeline: 2 years 
Recruitment of 100 CD patients with stenosis requiring EBD or EST over 1 years: 
follow up over 1 year. 
Patient privacy 
An organized database for the purpose of this study will be formed based on google 
form with anonymize data set (i.e. name, address, and full post code will be removed, 
together with any other information which, in conjunction with other data held by or 
disclosed to the recipient, could identify the patient) which would be entered by clini-
cal research assistant.
Study design 
Study type: Interventional (clinical trial)
Estimated enrolment: 100 patients 
Allocation: Randomized 
Intervention model:  Parallel assignment 
Masking: none (open label) 
Primary purpose: Therapeutic  
Official title: Randomized controlled trial comparing endoscopic balloon dilation 
versus endoscopic stricturotomy for short strictures (< 3 cm) related to Crohn’s dis-
ease (the BEST-CD trial)
Estimated start date : August - September 2022 (after ethical approval) 

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Estimated recruitment completion: July - August  2023
Estimated study completion date: July - August  2023
Arms and interventions: 
Arm 
Intervention/treatment 
Active comparator: 
Confirmed Crohn’s disease 
with gastro-duodenal or ileo-
colonic short (<3 cm) 
strictures (both de novo and 
anastomotic) without prior 
history of endoscopic 
stricture therapy 
Intervention: Endoscopic balloon dilation 
EBD procedures will be performed with wire 
guided CRE pneumatic balloon (controlled radial 
expansion balloon, Boston scientific, Marlborough, 
MA, USA 0of various sizes based on tightness of 
the stricture (10-12 mm, 12-15 mm, 15-18 mm, 
18-20 mm) with graded dilations with inflation 
pressures varying from 3-8 ATM pressure. Balloon 
was inflated for at least 2 minutes and slowly 
deflated. A maximum of two sessions of dilation 
will be allowed with a minimum interval of 15-30 
days between them.

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Outcome measures 
Primary outcome measures 
To compare sustained clinical improvement post EBD and ES (%) (time frame : 
Active comparator 
Confirmed Crohn’s disease 
with gastro-duodenal or ileo-
colonic short (<3 cm) 
strictures (both de novo and 
anastomotic) without prior 
history of endoscopic 
stricture therapy
Intervention: Endoscopic stricturotomy with or 
without stricturoplasty 
Endoscopic stricturotomy would be done using 
either a tri- ple-lumen needle-knife (Boston 
Scientific, Marlborough, MA) or with a 
electrosurgical IT knife2 (Olympus Medical 
Systems, Tokyo, Japan) in the setting of ERCP 
Endocut on ERBE (USA Incorporated Surgical 
Systems, Marietta, GA) with the following 
electrocautery settings: Endocut Q (effect 3, cut 
duration 1, cut interval 3). Strictures will be incised 
in a circumferential or radial fashion until an 
adequate passage of the scope. Endoclips may be 
applied post stricturotomy to act as keep treated 
stricture open and to prevent delayed bleeding 
(referred as stricturoplasty). Choice of endoclips 
and decision to perform stricturoplasty would be at 
the discretion of endoscopist.

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1year): percentage of patients having no obstructive symptoms due to CD related 
stenosis for which EBD/ES was performed for a period of 1 year  
Secondary outcome measures 
1. To compare need for additional intervention (EBD/EST/Surgery) between EST and 
EBD arm (%) : the percentage of patients who require additional interventions for 
CD related stenosis over period of 1 year 
2. To compare technical success between EBD and ES (%): Percentage of patients in 
whom endoscope is passable after EBD/ES 
2. To compare stricture related visit to the emergency department after EST versus 
EBD: percentage of patients visiting the emergency department for CD stenosis relat-
ed symptoms post EBD/ES over period of 1 year  
3. To compare structure related hospitalization with EST versus EBD: percentage of 
patients visiting undergoing hospitalization for CD stenosis related symptoms post 
EBD/ES over period of 1 year  
4. To compare complications related to EST versus EBD: Major adverse events will 
be defined as perforation, bleeding requiring transfusion or any procedure related pro-
longation of hospitalization period or an endoscopic, radio logic or surgical interven-
tion. Minor adverse events were bleeding not requiring blood transfusion, post pro-
cedural pain and any other self limiting complication which does not warrant prolon-
gation of hospital stay. Adverse events were considered associated to be with the pro-
cedure when a causal association was possible, probable, or definite.
Eligibility criteria 
Ages eligible for the study : 18 Years to 65 Years   (Adult, Older Adult)
Sexes eligible for the study: all

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Accepts healthy volunteer: no 
Criteria

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Inclusion Criteria:
	 Primary confirmed diagnosis of CD with obstructive symptoms 
1) Gastro-duodenal and ileo-colonic strictures (both de novo and anastomotic stric-
tures)

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2) Short strictures (<3 cm) 
3) Fibrotic or mixed stricture (predominantly fibrotic)
4)  Strictures treated with either EST or EBD. 
Exclusion Criteria:
1. No established diagnosis of CD; 
2. No endoscopic therapy; and 
3. A combination therapy of EST and EBD at the onset
4. Small bowel CD related stricture requiring enteroscopy guided dilation
5. Predominantly ulcerated strictures (mixed or pure ulcerated strictures)   
6. Long strictures (>3 cm) 
7. Pediatric Patients (<18 years) 
8. Pregnant or lactating mother 
7. Not willing to participate
Studies on ESTST vs EBD CD related anastomotic strictures 

Experience of the key project personnel
Dr. PARTHA PAL, MD, DNB, MRCP (UK)) : Consultant Gastroenterologist with 
special interest in IBD research at IBD Center, Asian Institute of Gastroenterology, 

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Hyderabad India. He runs the IBD Clinic at the AIG, Somajiguda unit with an estab-
lished IBD registry and is actively involved in research in the field of IBD with nu-
merous publications. He is also a co-investigator of numerous clinical trials in IBD.
Declaration of Investigator 
I have read and understood all sections of the protocol entitled “Randomized con-
trolled trial comparing endoscopic balloon dilation versus endoscopic stricturotomy 
for short strictures (< 3 cm) related to Crohn’s disease (the BEST-CD trial)” in  the 
accompanying investigator’s brochure. I agree to supervise all aspects of the protocol 
and to conduct the clinical investigation in accordance with the Final Protocol Version 
including country specific dated    the International Council for Harmonization har-
monized tripartite guideline E6(R2): Good Clinical Practice and the Declaration of 
Helsinki (WMA2013), and all applicable government regulations. I will not make 
changes to the protocol before consulting implement protocol changes without inde-
pendent ethics committee approval except to eliminate an immediate risk to patients. I 
agree to perform the procedure only to patients under my personal supervision or the 
supervision of a sub-investigator. Confidentiality will be protected. Patient identity 
will not be disclosed to third parties or appear in any study reports or publications.
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Signature of Principal Investigator                                                               Date 
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Printed Name of Principal Investigator