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

Sponsor

Universitätsklinikum Hamburg-Eppendorf (Other)

Overall Status

Recruiting

CT.gov ID

NCT05029934

Collaborator

(none)

440

Enrollment

Locations

Arms

27.4

Anticipated Duration (Months)

110

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Wound Endoscopical, Colon After Polyp Resection, Colon	Procedure: use of EndoClot	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

440 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

use of EndoClot adhesive after resection vs no use of any preventive action against delayed bleeding (conrol group)use of EndoClot adhesive after resection vs no use of any preventive action against delayed bleeding (conrol group)

Masking:

Single (Participant)

Masking Description:

Patients will not be informed about the use of EndoClot adhesive

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Aug 18, 2021

Anticipated Primary Completion Date :

Aug 30, 2023

Anticipated Study Completion Date :

Nov 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: EndoClot group patients who are being provided with EndoClot adhesive spray after polyp resection	Procedure: use of EndoClot deployment of EndoClot adhesive spray
Sham Comparator: Conrol group no further prophylactic bleeding prevention after polyp resection	Procedure: use of EndoClot deployment of EndoClot adhesive spray

Arm

Intervention/Treatment

Active Comparator: EndoClot group

patients who are being provided with EndoClot adhesive spray after polyp resection

Procedure: use of EndoClot

deployment of EndoClot adhesive spray

Sham Comparator: Conrol group

no further prophylactic bleeding prevention after polyp resection

Procedure: use of EndoClot

deployment of EndoClot adhesive spray

Outcome Measures

Primary Outcome Measures

delayed bleeding complication: hospitalization [30 days]
hospitalization after subsequent return to unit / health care facility for evaluation of rectal bleeding
delayed bleeding complication: transfusion [30 days]
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
delayed bleeding complication: repeat endoscopy [30 days]
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
delayed bleeding complication: [30 days]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 89 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 INR (International Normalized Ratio) ≥1.5, or platelets <50
Poor bowel preparation
pregnancy or breastfeeding
Intervention planned using ORISE™ (Boston Medical) or LIFTUP™ (Ovesco) as lifting agents

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Vivantes Auguste-Viktoria-Klinikum	Berlin	Germany	12099
2	University Hospital Hamburg Eppendorf	Hamburg	Germany	20246
3	UKGM Marburg, Klinik für Gastroenterologie	Marburg	Germany	35043
4	Klinikum Südstadt Rostock	Rostock	Germany	18059