A 4-arm Randomized Controlled Trial of Fuse®, EndoCuff™, EndoRings™ and Standard Colonoscopy
Phase: NA
Conditions: Colorectal Neoplasms
Sponsor: Indiana University

Protocol for 4-arm study 
 
NCT02345889 
Version 3; 4/9/2015 
 
A 4-arm randomized controlled trial of Fuse, EndoCuff, EndoRings and standard colonoscopy for 
improving adenoma detection rates. 
Protocol: 
Introduction: 
ADR (Adenoma detection rate or percentage of patients with at least one adenoma among all 
colonoscopies performed by a doctor) was first proposed as a quality indicator 12 years ago. It has now 
been validated as an excellent marker for the risk of interval colorectal cancer (cancer occurring after 
colonoscopy). Although colonoscopy offers protection from colorectal cancer for at least a decade and 
more, this protection has been shown to vary depending on the location and type of pre-cancerous 
lesions and the training and skill of the doctor performing the procedure. A recent large study of more 
than 200,000 colonoscopies found that every 1% increase in ADR resulted in a decrease of interval CRC 
by 3% and fatal interval CRC by 5%. Although the increase was linear the effect was more pronounced 
once the ADR reaches 28% and continued beyond till 52%. 
Measures to improve ADR are therefore a worthy goal to study. Recent studies indicate that continuing 
medical education, time of colonoscopy during the day, forced longer withdrawal time, use of high 
definition colonoscopes all result in improving ADR although the gains have only been modest. To this 
end, adding novel devices to the tip of colonoscope may improve the ability of doctors to perform a 
better procedure. We therefore propose to identify the increase in ADR with 3 of these devices 
compared to standard colonoscopy. Fuse colonoscopy (2 cameras embedded at the side of the 
colonoscope tip providing an increased angle of view), EndoCuff (a plastic cap to fit the tip with flexible 
arms which hold the mucosa back aiding in inspection), EndoRings (similar to EndoCuff but the arms are 
wider) have been shown in tandem colonoscopy studies to improve the adenoma miss rates to 7-15% 

Protocol for 4-arm study 
 
NCT02345889 
Version 3; 4/9/2015 
 
instead of the miss rates seen with standard colonoscopy which is usually about 40%. All these devices 
are FDA approved and are distributed in the United States. 
Methods: 
Persons scheduled for a standard screening, surveillance or diagnostic colonoscopy at the Glen Lehman 
Endoscopy Suite will be invited to participate in the study after a member of the research team explains 
the risks, benefits and the choice of not participating in research. 
If the patient qualifies after being screened for exclusion criteria as listed below, they will be given an 
informed consent document and an authorized HiPAA form to sign. Once both documents are signed, a 
copy will be provided to the patient and then the patient is randomized to undergo a standard 
colonoscopy, a Fuse colonoscopy, colonoscopy with EndoCuff or a colonoscopy with EndoRings. 
Study procedures: 
Patients will undergo a split dose bowel preparation starting the evening before the procedure day and 
ending at least 4 hrs. prior to the procedure.  Patients with medical indicators of inadequate bowel 
preparation are given a more intensive regimen sometimes doubling the dose of preparation drug. 
Patients agreeing to participate will be randomized to one of the four study arms prior to initiation of 
colonoscopy.  
A colonoscope will be introduced and advanced to the cecum at which time a research assistant will 
note the time taken to achieve this. Once the withdrawal starts, the same assistant will start a stop 
watch which will be stopped for any cleaning of the bowel or polypectomy procedures. In this way 
inspection time can be monitored for all arms of the study.  

Protocol for 4-arm study 
 
NCT02345889 
Version 3; 4/9/2015 
 
After randomization, a patient can be withdrawn due to condition discovered during colonoscopy which 
places the patient in the exclusion criteria, an inadequate bowel preparation as determined by the 
performing doctor or a request from the patient to be withdrawn. 
 
Inclusion criteria: 
Screening colonoscopy, Surveillance colonoscopy or diagnostic colonoscopy and >=50 years of age 
Exclusion criteria: 
Any personal h/o large bowel resection, inflammatory bowel disease, or polyposis syndromes 
Any family h/o polyposis syndromes 
Referral for an incomplete exam or polyp clearance 
Referral for a FOBT+ testing in the last 6 months 
Anticipated difficult colonoscopy 
 
Statistical analyses: 
We will perform analyses on the data after randomization and prior to withdrawal (intention to treat) 
and on data of patients completing the study (excluding the withdrawal patients, per protocol). 
The primary aim of increased ADR detection will be tested using a chi-square test among the four 
groups. 

Protocol for 4-arm study 
 
NCT02345889 
Version 3; 4/9/2015 
 
The secondary aims of cecal intubation rates, cecal insertion time and detection of serrated and flat 
lesions will be tested using chi-square, t-test, and chi-square respectively. 
All analyses will be performed on SPSS Version 20 (IBM, NY). 
Sample size: 
The ADR of the principal investigator has averaged about 40% in published studies. We hope to achieve 
a 10% increase in the ADR with these newer devices when compared to standard colonoscopy. 
Using a 4-arm RCT, to detect a 10% increase from a baseline of 40%, we require 388 patients in each 
arm at an ἀ level of 0.05 with 80% power (n=1552). To account for the withdrawals after randomization, 
which would amount to an average of 6% per our recent studies, we will need to enroll 412 patients in 
each arm (n=1648). 
Ethical considerations: 
 All protocols will be approved by the local IRB before starting the research study. An informed consent 
document will be provided to each patient to review for participating in the study. An express 
authorization to review medical data for research purposes will be obtained before randomizing any 
patient. All patients will be provided with a contact number in case of questions or if they wish to inform 
of their intent to be withdrawn. 
Adverse events:  
The primary investigator will monitor any adverse event reported to the study staff and determine if it’s 
related to the study procedures including standard colonoscopy. All adverse events will be monitored 
until a satisfactory resolution and will be reported to the IRB within 5 days of knowledge. 

Protocol for 4-arm study 
 
NCT02345889 
Version 3; 4/9/2015 
 
A table will be maintained for the adverse events in each arm and in case of any statistically significant 
adverse event rate in any arm, the primary investigator will make the decision to remove the treatment 
arm or stop the study. 
 
Data integrity and safety: 
 All paper charts pertaining to the patient will be kept under lock and key in coordinators office away 
from the endoscopy area. The data entry will be performed into an excel file which will be stored on an 
internal network drive with encryption and password security. Only approved personnel by the IRB will 
have access to the file storage. This file will also not have any identifiable information (name, DOB or 
mrn). A study log with the identifiable information will be kept in a separate folder (also encrypted) to 
enable the investigators to assist in any research audit. No procedural data except the date of 
examination will be entered into this log.