Clinical trial NCT05029934: Efficacy of EndoClot™ Spraying After Endoscopic Resection of Large Colorectal Polyps
Official title: Efficacy of EndoClot™ Spraying After Endoscopic Resection of Large Colorectal Polyps: A Randomized Trial.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Wound Endoscopical, Colon
After Polyp Resection, Colon
Keywords: colon endoscopic mucosa resection (EMR)
delayed bleeding
colonoscopy
polyp resection
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
First posted: 2021-09-01
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: use of EndoClot adhesive after resection vs no use of any preventive action against delayed bleeding (control group)
Primary purpose: PREVENTION

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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: delayed bleeding complication: hospitalization
timeFrame: 30 days
measure: delayed bleeding complication: transfusion
timeFrame: 30 days
measure: delayed bleeding complication: repeat endoscopy
timeFrame: 30 days
measure: delayed bleeding complication:
timeFrame: 30 days
Secondary outcomes:
measure: Technical handling
timeFrame: 20 minutes (assumed deployment time)
measure: Overall complications
timeFrame: procedure to day 30
measure: Factors associated with complications: polyp size
timeFrame: 30 days
measure: Factors associated with complications: polyp location
timeFrame: 30 days
measure: Factors associated with complications: polyp histology
timeFrame: 30 days
measure: Factors associated with complications: polyp morphology
timeFrame: 30 days
measure: Factors associated with complications: polyp resection time
timeFrame: 30 days
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Vivantes Auguste-Viktoria-Klinikum
city: Hamburg
country: Germany
facility: University Hospital Hamburg Eppendorf
city: Hamburg
country: Germany
facility: Evangelisches Amalie Sieveking Krankenhaus
city: Marburg
country: Germany
facility: UKGM Marburg, Klinik für Gastroenterologie
city: Rostock
country: Germany
facility: Klinikum Südstadt Rostock
Study officials:
References:
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