Efficacy of EndoClot™ Spraying After Endoscopic Resection of Large Colorectal Polyps

Study Overview
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Brief Summary
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The effectiveness of colonoscopy in reducing colorectal cancer mortality relies on the detection and removal of neoplastic polyps. Effective and safe resection of larger polyps is particularly important due to their higher potential of malignancy. Large polyps ≥20mm are removed by so-called endoscopic mucosal resection (EMR) (and occasionally endoscopic submucosal dissection (ESD)) using electrocautery snares. Resection of these large polyps is associated with a risk of severe complications that may require hospitalization and additional interventions. The most common risk is delayed bleeding which is observed in approximately 2-10% of patients. In a recent randomized trial, clipping has been shown to reduce bleeding esp. on the right colonic side. However, clipping of larger areas is time consuming and may add to costs in several ways. Our primary aim is to examine whether EndoClot™ application (a special form of longer lasting spray on the mucosal defect after EMR/ESD of large non-pedunculated colorectal polyps (≥20mm) will reduce the risk of delayed bleeding. We hypothesize that EndoClot™ application will reduce the risk of delayed bleeding by at least 3/4 (i.e. from 7.5% to 1.5%) based on an initial assumption of a 7.5% delayed bleeding rate.

Detailed Description
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Colorectal cancer is the second most common cause of cancer death in the United States and Europe. The effectiveness of colonoscopy in reducing the risk of dying from colorectal cancer relies on the detection and safe resection of neoplastic polyps to prevent incident cancers. Most polyps are small and can be easily removed using snare with or without electrocautery. Because the risk of prevalent cancer or transition to cancer increases with polyp size, effective and safe resection of large polyps is particularly important. Endoscopic mucosal resection (EMR) is evolving as the primary endoscopic technique to remove large non-pedunculated polyps. These flat or sessile polyps are defined as lateral spreading tumors with a low vertical axis that extend laterally along the luminal wall. Several mostly retrospective studies from Europe, the U.S. and Japan, have demonstrated a high cure rate, with results lending credence to the shift from surgical resection to endoscopic management of these lesions. Of concern, however, is 1) a fairly high overall complication rate of 8-26% in prospective studies3-7, and 2) as well the persistence of residual neoplasia on follow-up endoscopy ranging from 16% to 46%3, 6, 8. The former is the main topic of the present study. Severe complications including bleeding associated with a standard diagnostic or screening colonoscopy, which may include resection of predominantly smaller polyps, are uncommon. Significant bleeding occurs in 0.2 to 0.5% of patients (defined as a 2mg drop in Hemoglobin) 9, 10. The risk of severe complications increases with polyp size; here, again, the most common complication is bleeding reported in 2 to 24% of polyp resections. In one recent analysis the rate of delayed bleeding in colonic EMR was 7.5%1. In addition to size, other factors may affect complications. These include type of resection (piecemeal versus en-bloc), polyp location (right colon with a thinner wall than the left colon), age and comorbidities, especially those that affect clotting abilities (e.g. renal insufficiency, liver disease, use of anticoagulation). Studies that have examined variables, which may directly decrease the risk of complications associated with large polyp resection, are limited. It is apparent that resection of a large polyp leaves behind a large mucosal defect. The mucosal ulcer that forms after polyp resection can take several weeks to heal. Bleeding complications typically occur within 7 to 10 days, requiring often admission, a repeat colonoscopy to stop bleeding, and possible blood transfusions. The rates depend on size, and have been shown to be around 1.5%-2.6% overall. It is significantly higher in larger adenomas of 2 cm and more, namely 6.5% in another recent meta analysis. To reduce the risk of bleeding various measures have been proposed which also have been summarized in several recent meta analyses. These include coagulation, clipping and others, but only few randomized trials are available: Coagulation not effective in a recent meta analysis14, but only 4 of the 12 studies were randomized and these included all mostly smaller polyps or polyps of all sizes or pedunculated polyps. In a recent randomized trial, clipping has been shown to reduce bleeding esp. on the right colonic side. However, clipping of larger areas is time consuming and may add to costs in several ways. Our primary aim is to examine whether EndoClot™ application (a special form of longer lasting spray on the mucosal defect after EMR/ESD of large non-pedunculated colorectal polyps (≥20mm) will reduce the risk of delayed bleeding. We hypothesize that EndoClot™ application will reduce the risk of delayed bleeding by at least 3/4 (i.e. from 7.5% to 1.5%) based on an initial assumption of a 7.5% delayed bleeding rate.

Official Title
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Efficacy of EndoClot™ Spraying After Endoscopic Resection of Large Colorectal Polyps: A Randomized Trial.

Conditions
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Wound Endoscopical, Colon, After Polyp Resection, Colon

Intervention / Treatment
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* Procedure: use of EndoClot


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a ≥20mm colon non-pedunculated polyp who are undergoing an ESD or EMR resection signed Informed Consent Exclusion Criteria: Patients with known (biopsy proven) or strongly suspected invasive carcinoma in a potential study polyp Pedunculated polyps (as defined by Paris Classification type Ip or Isp) ulcerated depressed lesions (as defined by Paris Classification type III) polyposis syndromes inflammatory bowel disease emergency colonoscopy Poor general health (ASA (American Society of Anaesthesiologists) class>3) Patients with coagulopathy with an elevated International Normalized Ratio (INR )≥1.5, or platelets <50 Poor bowel preparation pregnancy or breastfeeding Intervention planned using ORISE™ (Boston Medical) or LIFTUP™ (Ovesco) as lifting agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: use of EndoClot adhesive after resection vs no use of any preventive action against delayed bleeding (control group)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EndoClot group<br>patients who are being provided with EndoClot adhesive spray after polyp resection | Procedure: use of EndoClot<br>* deployment of EndoClot adhesive spray<br>|
| Sham Comparator: Control group<br>no further prophylactic bleeding prevention after polyp resection | Procedure: use of EndoClot<br>* deployment of EndoClot adhesive spray<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| delayed bleeding complication: hospitalization | hospitalization after subsequent return to unit / health care facility for evaluation of rectal bleeding | 30 days | 
| delayed bleeding complication: transfusion | a patient who subsequently had to return to the unit and/or any health care facility for evaluation of rectal bleeding AND who required transfusion | 30 days | 
| delayed bleeding complication: repeat endoscopy | a patient who subsequently had to return to the unit and/or any health care facility for evaluation of rectal bleeding AND who required a repeat colonoscopy or sigmoidoscopy for examination of the polypectomy site or control of bleeding | 30 days | 
| delayed bleeding complication: | a patient who subsequently had to return to the unit and/or any health care facility for evaluation of rectal bleeding AND who required surgery | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Technical handling | product deployment assumed quantity of entire vial: < 50%/50-70%/100% | 20 minutes (assumed deployment time) | 
| Overall complications | an aggregate of all complications that occur at the time of the procedure or during follow-up | procedure to day 30 | 
| Factors associated with complications: polyp size | Factors that may be associated with complications, esp. bleeding | 30 days | 
| Factors associated with complications: polyp location | Factors that may be associated with complications, esp. bleeding: location of the polyp in the colon (right, left, rectum) | 30 days | 
| Factors associated with complications: polyp histology | Factors that may be associated with complications, esp. bleeding | 30 days | 
| Factors associated with complications: polyp morphology | Factors that may be associated with complications, esp. bleeding | 30 days | 
| Factors associated with complications: polyp resection time | Factors that may be associated with complications, esp. bleeding | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colon endoscopic mucosa resection (EMR), delayed bleeding, colonoscopy, polyp resection