Clinical Study to Compare Cold Snare Underwater Polypectomy to Cold Snare Conventional Polypectomy for Colon Polyps [COLDWATER Study] (COLDWATER)

Randomized Clinical Trial to Compare Underwater Cold Snare Polypectomy (UCSP) to Conventional Cold Snare Polypectomy (CCSP) for Non Pedunculated Colon Polyps of Size 5-10mm [COLDWATER Study]

Colon cancer is internationally the third cause of deaths from a malignant disease. Screening colonoscopy in adults >45 years of age aims at the early diagnosis and treatment colon polyps that are precancerous lesions. Endoscopic polyp removal (polypectomy) can be done with various techniques depending on the size, morphology, location of the polyp etc. According to updated guidelines, non-pedunculated polyps of small size are treated with a cold snare in air dilated intestinal lumen (conventional cold snare polypectomy - CCSP).In recent years, several studies have described the benefits of water aided colonoscopy, as well as safety and efficacy of underwater polypectomy in large colon polyps. However, there is not enough data on small polyps which are the most commonly diagnosed.This is a prospective randomized double-blind clinical trial to compare the safety and efficacy of CCSP to underwater cold snare polypectomy (UCSP)for non-pedunculated polyps of size of 5-10 mm. A total of 398 polyps will be randomized and randomization will be performed via random numbers method of Microsoft Excel 2016. Primary outcome of this study is to determine muscularis mucosa resection rate. Secondary outcomes are the depth and percentage of R0 excisions and possible complications.

The investigators expect UCSP to ensure a higher muscularis mucosa resection rate and they attempt to examine the resection depth in the submucosal layer.These results will provide useful data for the development of guidelines in polypectomy techniques for non-pedunculated polyps 5-10mm.

Study Overview

• Status: Active, not recruiting
• Conditions: Polypectomy; Colon Polyps
• Intervention / Treatment: Procedure: Underwater Cold Snare Polypectomy; Procedure: Conventional Cold Snare Polypectomy

• Study Type: Interventional
• Enrollment (Actual): 396
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 15126
    • Sismanogleio General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age > 20years
2. Non pedunculated polyps (Paris classification Isp, Is, IIa, IIb)
3. Polyp size: diameter of 5 to 10mm
4. Endoscopic diagnosis of mucosal lesions - must not present malignant submucosal infiltration evidence like deepening, ulceration / ulcer, abnormal vessels, irregular surface, (NICE 1, NICE 2A, BASIC)
5. Informed consent
6. Patients who receive antiplatelet / anticoagulant therapy are included in the study only if their therapy has been modified according to ESGE guidelines

Exclusion Criteria:

1. Age <20 years old
2. Pedunculated polyps
3. Lesions with macroscopic elements of high-grade dysplasia or submucosal infiltration
4. Sites with previous polypectomy
5. Patients with idiopathic inflammatory bowel disease
6. Patients with coagulation disorders
7. Patients with severe organ failure

7.Patients who during endoscopy will undergo any technique using electrocautery / electrocoagulation will not be eligible for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Underwater cold snare polypectomy group; Cold snare polypectomy after complete immersion of the polyp in the water	Procedure: Underwater Cold Snare Polypectomy; The procedure of Underwater Cold Snare Polypectomy (UP) will be as follows: Complete suction of air from the intestinal tract; Partial opening of the intestinal lumen by using sterile room temperature water via a water pump; Complete immersion of the lesion in water; Snaring of the lesion and a small amount of surrounding healthy tissue (1-2mm); Excision The objective will be the en bloc resection of the lesion including healthy tissue (about 2mm). If the en bloc resection fails, a piecemeal will be performed on as few specimens as possible
Active Comparator: Conventional cold snare polypectomy group; Cold snare polypectomy in colon lumen dilated with air	Procedure: Conventional Cold Snare Polypectomy; The procedure of Conventional Cold Snare Polypectomy (CCSP) will be as follows: If the entry during the endoscopy has been made with water, the water will be aspirated, and the intestinal lumen will be re-stretched using air / CO2; Snaring of the lesion and a small amount of surrounding healthy tissue (1-2mm); Excision The objective will be the en bloc resection of the lesion including healthy tissue (about 2mm). If the en bloc resection fails, a piecemeal will be performed on as few specimens as possible

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of muscularis mucosa included in specimen (%)	Determination of percentage of muscularis mucosa included in specimen. The determination of the percentage of the area containing muscularis mucosa layer will be done by measuring the length of muscularis mucosa mm / length of specimen mm x100%. Using an ocular and stage micrometer, the length of the muscularis mucosa underlining a neoplastic lesion was measured, along with the specimen's maximum diameter (mm)	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence or absence of submucosal in the specimen and its depth (if present)	Presence or absence of submucosa - Measurement of submucosa depth in μm (when submucosa is present in the specimen)	through study completion, an average of 1 year
Percentage of R0 Resections	Vial 1 : Determination of polypectomy margin according to Residual Tumor Classification Vial 1A : Determination of horizontal margins: presence of residual damage or not In order to determine the horizontal margins, 2-4 biopsies will be taken from the resection area (2 biopsies antidiametrically in polyps of 5-7 mm size, 4 biopsies in polyps of 8-10 mm size). One cup of forceps will be placed in the defect and the second in the macroscopically normal mucosa. The received tissue pieces will be placed in a new vial with formol (Vial 1A) A microscopically margin-negative resection will be characterized as "R0 resection" The determination of R0 Resection Rate will be done by measuring the number of R0 resections / number of all the resections regardless R classification	through study completion, an average of 1 year
Complication rate	intraprocedural bleeding, post-procedural bleeding, perforation, abdominal pain not due to perforation. These complications will be evaluated by a study physician of the Gastroenterology Department with a phone call and clinical examination if needed	30 days after the polypectomy (treatment procedure)
Recurrence lesion rate during repeat colonoscopy in 6-12months	A subgroup of the sample size will undergo a follow up colonoscopy in 6-12 months in order to identify lesion recurrence	6-12 months after polypectomy (treatment procedure)

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Investigators: Principal Investigator: Maria Zachou, MD,Msc, Department of Gastroenterology, General Hospital of Athens Sismanogleio, Greece; Study Director: Stylianos Kykalos, Assist.Prof, 2nd Department of Propaedeutic Surgery, National and Kapodistrian University of Athens, General Hospital Laiko, Athens, Greece; Study Chair: Evangelos Kalaitzakis, Assist.Prof, Department of Gastroenterology, University Hospital of Heraklion, University of Crete, Heraklion, Greece; Study Chair: Stavros Sougioultzis, Gastroenterology Unit, Department of Pathophysiology, School of Medicine, National and Kapodistrian University Athens, Greece

Publications and helpful links

General Publications

• Zachou M, Varytimiadis K, Androutsakos T, Katsaras G, Zoumpouli C, Lalla E, Nifora M, Karantanos P, Nikiteas N, Sougioultzis S, Kalaitzakis E, Kykalos S. Protocol design for randomized clinical trial to compare underwater cold snare polypectomy to conventional cold snare polypectomy for non-pedunculated colon polyps of size 5-10 mm (COLDWATER study). Tech Coloproctol. 2022 Nov 18. doi: 10.1007/s10151-022-02731-9. [Epub ahead of print]

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2022
• Primary Completion (Actual): December 11, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: February 9, 2022
• First Submitted That Met QC Criteria: March 9, 2022
• First Posted (Actual): March 10, 2022

Study Record Updates

• Last Update Posted (Estimate): December 13, 2022
• Last Update Submitted That Met QC Criteria: December 11, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: polypectomy; cold snare polypectomy; cold snare; colon polyps; underwater polypectomy
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Intestinal Polyps; Polyps; Colonic Polyps
• Other Study ID Numbers: PN61759

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Available from the corresponding author on reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No