Closure of Mucosal and Submucosal Defects in the Gastrointestinal Tract Using the Novel X-Tack Endoscopic Suturing Device
Phase: NA
Conditions: Polyp of Colon, Fistula
Sponsor: Thomas Jefferson University

RESEARCH PROTOCOL 
INVESTIGATOR INITIATED TREATMENT TRIALS 
Document date 4/8/2021 
 
Title of Project: Closure of mucosal and submucosal defects in the gastrointestinal 
tract using the novel X-Tack endoscopic suturing device 
 
Principal Investigator: 
Anand Kumar MD MPH, Department of Gastroenterology and 
Hepatology   
Co-Investigators:  
Thomas Kowalski MD, Department of Gastroenterology and Hepatology 
 
 
 
 
David Loren MD, Department of Gastroenterology and Hepatology 
 
 
 
 
Alexander Schlachterman MD, Department of Gastroenterology and Hepatology 
 
 
 
 
Austin Chiang MD MPH, Department of Gastroenterology and Hepatology 
 
 
 
 
Ian Holmes MD, Department of Gastroenterology and Hepatology 
 
 
 
 
Muhammad Bashir, Department of Gastroenterology and Hepatology   
 
 
 
 
 
Abstract 
 
Background: Perforation rates following endoscopic submucosal dissection (ESD) of 
colonic lesions can be as high as 4% with delayed bleeding rates of up to 8%, resulting 
in significant patient morbidity. Endoscopic closure of resection defects is the least 
invasive method for closure of perforations or fistulas and has been shown to reduce 
delayed bleeding rates. The X-Tack is a new system for endoscopic suturing that has 
been designed to be use through the operating channel of standard endoscopes, as 
opposed to the previous standard of care (the Overstitch system) which needed to be 
loaded onto a separate endoscope. 
Methods: Adult patients presenting for endoscopic closure of a gastrointestinal luminal 
defect will be enrolled and randomized 1:1 to closure of the defect with either the X-Tack 
system (the study group) or the Overstitch system (the control group.) Demographics, 
comorbidities, laboratory values, size of defect, time to close the defect, and the number 
of sutures to close the defect will be recorded. The primary outcome will be the time to 
closure of the defect. Secondary outcomes will include the rate of incomplete closures 
(as defined as either crossover to the other study group per endoscopist’s discretion, or 
the need for additional modalities to close the defect such as endoscopic clips) as well as 
complications (bleeding, infection, perforation) and costs. Time to closure will be 
compared using the student T-test. To detect a 5-minute mean difference between the 
two groups at 80% power with an alpha of 0.05 and 1:1 randomization, 16 patients will be 
required in each group. Anticipating loss of subjects or data for technical or unanticipated 
reasons after randomization, we expect that 50 patients will need to be enrolled. 
 
 
 
A. Specific Aims 
 
The primary objective of the study is to compare the time required to close a defect or 
fistula in the gastrointestinal tract between the X-Tack system and the current standard 
of care (suturing with the Overstitch system.) The secondary objectives of the study will 
be to compare the rate of incomplete closures (as defined as either crossover to the other 

study group per endoscopist’s discretion, or the need for additional modalities to close 
the defect such as endoscopic clips) as well as complications (bleeding, infection, 
perforation) and costs between the X-Tack system and the current standard of care. We 
hypothesize that the X-Tack system will permit faster closure of endoscopic defects 
compared to the current standard, because the X-Tack does not require a different 
endoscope to use. 
 
B.  Background and Significance 
 
Perforation rates with endoscopic submucosal dissection (ESD) of colonic lesions and 
early cancers can be as high as 4% with delayed bleeding rates up to 8%. Endoscopic 
closure of resection defects has been shown to reduce delayed bleeding rates in the colon 
and is the least invasive method for closure of perforations or fistulas. Current options for 
closure include through-the-scope (TTS) clips, over-the-scope clips (OTSC,) and 
endoscopic suturing with the Overstitch system. TTS clips frequently misdeploy or are 
dislodged during complex closures and are cumbersome for the closure of large defects. 
OTSC are limited to closure of ~2 cm defects but are unable to capture the entirety of 
larger defects. The Overstitch system can close defects of any size but requires the use 
of a double-channel endoscope that is wide in diameter and is often too short to reach 
the right colon. It also requires removal of the endoscope that is being used for the 
resection from the patient in order to introduce the double-channel scope for closure. The 
X-Tack system offers the ability to close large defects with endoscopic sutures but can 
be introduced through the instrument channel of any standard endoscope, filling the gap 
between clips and suturing. 
 
C.  Preliminary Studies/Progress Report   
 
The X-Tack is currently FDA cleared on the basis of similarity to previous suturing 
devices, though human data is pending. Preclinical animal data primarily compared the 
X-Tack to through-the-scope (TTS) clips. In the 24 X-Tack cases, 21 could be closed with 
just one X-Tack device, while a second device was used in 3 cases. Technical closure of 
defects in the animal model was successful in 24/24 cases using the X-Tack, versus just 
13/16 cases using TTS clips. On necropsy, the time to complete healing of the defects 
was comparable between the X-Tack and TTS clip cases. On this basis, the investigators 
concluded that the X-Tack achieved expected levels of tissue healing and higher technical 
success rates than the current standard of care. 
 
D.  Research Design and Methods 
 
Currently, the community standard is that gastroenterologists who are familiar with 
Overstitch start using the X-Tack without additional training. However, a hands-on 
demonstration session with the X-Tack device in a “dry lab” has been conducted with 
each endoscopist in the trial prior to the study in order to familiarize them with device 
before enrollment. Each endoscopist has also participated in a “wet lab” using an explant 
(porcine stomach) to simulate in vivo closure of defects using the X-Tack system. The 
device operates in a similar fashion compared to previous suturing devices, which are 

used frequently by all endoscopists involved in this study. On this basis, all endoscopists 
in the study report comfort and familiarity with the X-Tack system, and the “break-in” 
period is not anticipated to affect safety or results during the study. The primary study visit 
will be comprised of the endoscopic procedure at the time of defect closure and a 
telephone call 48-72 hours later to assess for complications. Patient will be enrolled in the 
pre-procedure area. If the patient has a pre-procedure visit, they may be notified of their 
potential for enrollment in the study at that time, though not all patients have a pre-
procedure visit in our practice. Patients will be randomized to closure with the X-Tack 
system versus closure with the Overstitch system prior to their procedure using a 
centralized computer-generated randomization. Technical success of closure, time of 
closure, number of sutures required, need for alternative modalities for closure, and any 
intraprocedural complications (bleeding, perforation) will be recorded. Any patient with 
possible periprocedural perforation will receive antibiotics at the endoscopist’s discretion. 
At the endoscopist’s discretion, the patient may cross over during the procedure to the 
other group if they believe that their current closure strategy is failing to safely close the 
defect. Alternate methods of closure (TTS clips, over-the-scope clips) may be used in 
either group if required by the endoscopist for safe closure of the defect. After the 
procedure, most patients are observed in the recovery area for 1-2 hours for any signs of 
complications before they are discharged home. 
 
 
 
 
 
E.  Statistical Methods   
 
Time to closure will be compared using the student T-test. To detect a 5-minute 
mean difference between the two groups at 80% power with an alpha of 0.05 and 
1:1 randomization, 16 patients will be required in each group (32 patients in total.) 
Anticipating loss to follow-up and patient dropout, we expect that a total of 50 
patients will be required. Categorical variables will be compared using the chi 
squared test. 
 
F.  Gender/Minority/Pediatric Inclusion for Research 
 
Women and minorities will be included in the research protocol. 
 
G.  Human Subjects 
1.  Provide number, age range, and health status of the subject population.  List 
criteria for inclusion or exclusion.  
 
Enrollment in 
pre-procedure 
area 
Endoscopic 
closure 
X-Tack (n = 16) 
Standard (n = 16) 
Follow-up 
telephone call 
in 48-72 hours 

We anticipate enrolling 50 patients in total. 
Inclusion criteria: Patients > 18 years of age undergoing closure of a 
gastrointestinal luminal defect for which a suturing device would be 
otherwise indicated. 
Exclusion criteria: INR > 2, platelets < 150, ongoing anticoagulation not meeting 
ASGE Antithrombotic Guidelines (Acosta RD et al, The Management of 
Antithrombotic Agents for Patients Undergoing GI Endoscopy, Gastrointest 
Endosc, 2016; 83(1): 3-16,) hemodynamic instability, ongoing or anticipated 
pregnancy 
 
2.  Identify sources of research material in the form of specimens, records or data.  
 
Records and data will include chart data including demographics and 
comorbidities, laboratory values, endoscopy reports, and video acquired 
during endoscopy. 
 
3.  Describe plans for recruitment and consent procedures to be followed. 
 
The endoscopist performing the procedure will meet the potential subject in the 
pre-procedure holding area. The endoscopist will review the consent documents 
with the potential subject. The subject will be provided time to review the entirety 
of the document and ask any questions of the endoscopist that they have. If they 
are amenable to proceeding, they will sign the consent and the procedure will be 
performed. No additional recruitment or inducement (i.e. advertising) is 
anticipated. 
 
4.  Describe risks and assess likelihood and seriousness. 
 
The primary potential risk of this research is device failure (i.e. failure to close 
defect or complications of closure, such as bleeding or perforation.) Device failure 
is expected to be uncommon. Most device failures are expected to be minor (i.e. 
perhaps requiring an additional device to complete closure of the rest of the defect, 
but no immediate harms or risks to the patient besides longer procedure time.) 
Serious complications (i.e. bleeding or perforation attributable to the device and 
requiring hospitalization) are expected to be very rare. 
 
5.  Describe procedures for protecting against or minimizing potential risks. 
 
 
Because the research device will be used for defect closure during the same period 
of sedation as the current standard of care, participants should not perceive any 
difference in their procedure beyond signing an additional consent form. Patients 
with a propensity for bleeding i.e. thrombocytopenia or coagulopathy will be 
excluded to avoid adverse events. 
 
6.  Describe potential benefits and importance to the subjects and others.   
 

Participants could potentially benefit from a faster defect closure with reduced 
anesthesia time. The ease of deployment of the X-Tack device also might make 
clinical success more likely. If the X-Tack device proves to be a faster, safer way 
to close mucosal defects or fistulas, future patients undergoing endoscopic 
submucosal dissection or fistula closure could benefit from less anesthesia time 
and a better chance at clinical and technical success. 
 
 
7.  Discuss why risks are reasonable in relation to benefits.  
 
The risks and side effects of closure with the X-Tack system are anticipated to be 
identical to those of the Overstitch system. Given that the Overstitch is the current 
standard of care, and the X-Tack is anticipated to be faster and more user-friendly, 
the benefits of introducing the X-Tack outweigh the risks. 
 
 
H.  Data and Safety Monitoring Plan   
 
1.  Data and Safety Monitoring Plan (DSMP) 
a. reporting mechanisms for adverse events to the IRB, FDA, and NIH. 
Adverse events will be tracked and reported to the IRB at the time of interim 
analysis and final analysis (anticipated study time is less than one year.) Adverse 
events will be defined as bleeding, infection, or perforation occurring within 72 
hours of the procedure. Severe adverse events will be reported to the IRB at the 
time of occurrence. Adverse events will be defined using the ASGE Adverse Event 
Lexicon (Cotton PB et al, A lexicon for endoscopic adverse events: report of an 
ASGE workshop. Gastrointest Endosc, 2010; 71(3): 446-454.) Severe adverse 
events in this lexicon are considered any adverse events resulting in hospital 
admission >10 days, ICU admission > 1 night, surgery for an adverse event or 
permanent disability. Severe adverse events will be reported using the OHR online 
portal. 
 
 
 
b. adverse event (AE) grading  
Adverse events will be graded according to the ASGE adverse event 
lexicon. 
 
 
 
c. plan for unanticipated AE reporting 
 
 
Severe adverse events will be reported to the IRB at the time of occurrence. 
 
 
 
d. plan for annual reporting of AEs 
The anticipated study time is less than one year, thus all reporting will occur 
at the time of interim analysis and final analysis. 
 
 
 
e. interim efficacy analysis where appropriate  
Perforation rate and complications related to inadequate closure (leak, 
fistula, peritonitis, bleeding) will be monitored. Perforation or complications 
related to inadequate closure > 50% compared to control group will lead to 

stoppage of the trial. Interim analysis will be performed at the midpoint of 
enrollment (25 patients.) For instance, if after 25 patients have enrolled, 2 
patients in the control group experience a complication, yet 4 experience a 
complication in the X-Tack group, the results will be reviewed with the 
independent safety monitor for possible stoppage of the trial pending 
discussion with the IRB. 
 
2.  If applicable, describe the Data and Safety Monitoring Board (DSMB) that will 
be responsible for monitoring the study.  
An independent reviewer has been selected within the Jefferson Division of 
Gastroenterology who is outside of the investigator group who will review the 
interim analysis. 
 
 
I.  Literature Cited 
 
1. Kothari ST., Huang RJ, Shaukat A et al. ASGE review of adverse events in 
colonoscopy. Gastrointest Endosc 2019;90:863-76 
2. Pohl H, et al. Clip Closure Prevents Bleeding After Endoscopic Resection of Large 
Colon Polyps in a Randomized Trial. Gastroenterology 2018;157:977-984.     
3. Qumseya BJ, Wolfsen C, Wang Y, et al. Factors associated with increased 
bleeding post endoscopic mucosal resection. J Dig Dis 2013;14:140–146.  
 
4. Cotton PB et al. A lexicon for endoscopic adverse events: reports of an ASGE 
workshop. Gastrointest Endosc 2010;71(3):446-454. 
 
Date   
 
 
 
Version  
 
 
 
Research Protocol Template, 11/15/2010