Clinical trial NCT03309683: Clip Placement Following Colonic Endoscopic Mucosal Resection (EMR)
Official title: Clip Placement Following Colonic Endoscopic Mucosal Resection (EMR). The CLIPPER Study: A Nationwide Multi-center Randomized Clinical Trail
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Polyp, Colonic
Bleeding
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: UMC Utrecht
name: Maastricht University Medical Center
name: Erasmus Medical Center
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Maxima Medical Center
name: Jeroen Bosch Ziekenhuis
name: Bernhoven Hospital
name: Isala
name: Canisius-Wilhelmina Hospital
name: Maasstad Hospital
name: Noordwest Ziekenhuisgroep
name: Meander Medisch Centrum
name: Catharina Ziekenhuis Eindhoven
name: Elisabeth-TweeSteden Ziekenhuis
name: St Jansdal Hospital
name: Leiden University Medical Center
name: Dutch Digestive Diseases Foundation
name: Franciscus Gasthuis
name: Bravis Hospital
First posted: 2017-10-13
Enrollment: 356
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Study design: A national, multi-center, patient-blinded, randomized clinical trial.

Study population: Patients undergoing EMR with a moderate to severe risk (right sided colon, ≥2cm) of developing Delayed Bleeding (DB).

Intervention: PC will be compared to standard care (no PC).

Main study endpoints: Primary endpoint is the incidence of DB. Secondary endpoints are cost-effectiveness, quality of life and (severe) adverse events related to PC, adenoma recurrence and risk factors for DB.

Detailed description: Design

This is a multi-center, randomized, patient-blinded multicenter trial, comparing two treatment strategies in 356 patients undergoing EMR for a colonic lesion 2-6 cm. The study will be enrolled in a selection of academic and non-academic Dutch hospitals. Patients undergoing an EMR will be a randomly allocated by web-based randomization to:

A) PC treatment group: minimally 1 clip per 1 cm of the polyp resection plane: OR B) Control group: standard care: only clip placement in case of uncontrollable bleeding (not successfully managed by coagulation) AND/OR perforation.

Population The target population in this proposal includes patients of 18 years and older, who gave written informed consent, undergoing EMR of a colonic polyp with a moderate to severe risk of developing DB. Moderate-severe risk of DB is defined as a laterally spreading or sessile polyp morphology proximal to the splenic flexure, measuring 2-6cm. Given the significantly increased risk of bleeding in the cecum, ascending and transverse colon, clip placement at this location may have the greatest benefit.

Inclusion Gastroenterologists from participating hospitals of the Dutch EMR Study Group will be asked to recruit patients for the trial. They will provide written information about the trial to potential participants, i.e., all patients scheduled for an EMR of a (right-sided) colonic polyp 2-6 cm, and 18 years or older. Members of the study group will contact potentially eligible patients at the outpatient clinic, hospital wards or by phone and give detailed information about the trial. In- and exclusion criteria will be checked and questions about the trial will be answered. Eligible patients will be invited to participate. After both the patient and the study physician or nurse practitioner have signed the informed consent form, in- and exclusion criteria will be checked again and baseline measurements will be performed, which include disease specific questionnaires including risk-factors for DB (AC use, restarting AC, polyp size, visible vessel, etc) and generic and disease specific quality of life questionnaires (see below). Patient's contact details will be provided to the study center for randomization.

Standard of care (usual care) In Dutch common practice, PC is not standard of care. PC is used, based on the personal preference of the endoscopist, mostly in case of intra-procedural bleeding/(possible)perforation. In our study group the minority of endoscopists applies PC after EMR in case of high risk patients, defined as right-sided flat polyps of at least 2cm and on AC or AP therapy.

Definition clinical significant delayed bleeding (DB)

DB is defined as any bleeding occurring after the completion of the procedure necessitating blood transfusion, hospitalization, or re-intervention (either repeat endoscopy, angiography, or surgery). Self-limiting bleeding managed on an outpatient basis is not included. Severity of DB Severity of bleeding is defined according to the ASGE working party document for adverse events in colonoscopy:

1. Mild DB: any post-EMR medical consultation, unplanned hospital admission, or prolongation of hospital stays for 3 days or fewer.
2. Moderate DB: unplanned hospital admission of 4 to 10 days, transfusion, repeat endoscopy, any interventional radiology procedure, or intensive care unit (ICU) admission for 1 night.
3. Severe DB: admission to the ICU for more than 1 night, unplanned admission for more than 10 nights, surgery, or permanent disability.

Treatment of DB DB is primarily treated by resuscitation. In case of resuscitation failure, colonoscopy, angiography with coiling and eventually surgery may be applied to control the bleeding site.

Follow-up After the EMR patients are contacted at 30, 90 and 180 days (short-term and long-term effects). At 180 days a colonoscopy is scheduled to access the adenoma recurrence rate (standard of care).

Eligibility criteria: Inclusion Criteria:

* laterally spreading or sessile polyp morphology (Paris classification 0-IIa/b/c) proximal to the splenic flexure, measuring 2-6 cm
* All patients aged \>18 years undergoing an EMR
* Written informed consent

Exclusion Criteria:

* Previous resection or attempted resection of a lesion less than 30 days ago or in the same session,
* Clip deployed prior to the completion of the EMR for a perforation or a major intra-procedural bleeding not treatable by coagulation,
* Endoscopic appearance of invasive malignancy (non-lifting Kato D, Kudo V pit pattern),
* Pregnancy,
* Active inflammatory colonic conditions (e.g. inflammatory bowel disease),
* Insufficiently corrected anticoagulants AND/OR a clotting disorder (platelet count \<50x109/l, INR \> 1,5),
* American Society of Anesthesiology (ASA) Grade IV-V,
* Macroscopic non-radical resection,
* \>1 lesion in 1 session,
* Involvement of valvula Bauhin or appendiceal orificium

Primary outcomes:
measure: Delayed bleeding
timeFrame: 30 days
Secondary outcomes:
measure: Adenoma recurrence
timeFrame: 180 days
measure: Cost-effectiveness
timeFrame: 180 days
measure: EMR scar evaluation
timeFrame: 180 days
Other outcomes:
Locations:
city: Harderwijk
country: Netherlands
facility: Ziekenhuis St Jansdal
state: Gelderland
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Erwin JM Van Geenen, dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Turan AS, Moons LMG, Schreuder RM, Schoon EJ, Terhaar Sive Droste JS, Schrauwen RWM, Straathof JW, Bastiaansen BAJ, Schwartz MP, Hazen WL, Alkhalaf A, Allajar D, Hadithi M, van der Spek BW, Heine DGDN, Tan ACITL, de Graaf W, Boonstra JJ, Voogd FJ, Roomer R, de Ridder RJJ, Kievit W, Siersema PD, Didden P, van Geenen EJM; Dutch EMR Study Group. Clip placement to prevent delayed bleeding after colonic endoscopic mucosal resection (CLIPPER): study protocol for a randomized controlled trial. Trials. 2021 Jan 18;22(1):63. doi: 10.1186/s13063-020-04996-7.