A Trial on Prophylactic Clipping to Prevent Post-polypectomy Bleeding After Colonoscopy in Direct Oral Anticoagulant Users (PROCLIP)

A Double Blinded Randomized Controlled Trial on Prophylactic Clipping to Prevent Post-polypectomy Bleeding After Colonoscopy in Direct Oral Anticoagulant Users

The investigators hypothesize that prophylactic clipping after colonoscopic polypectomy can reduce risk of delayed PPB among DOAC users. The investigators also hypothesize that pre-endoscopy drug level can predict the risk of hemorrhagic complications after the procedure.

Study Overview

• Status: Recruiting
• Conditions: Post Polypectomy Bleeding
• Intervention / Treatment: Procedure: Endoclip

Detailed Description

Despite the clinical benefit of colonoscopic polypectomy, post-polypectomy bleeding (PPB) occurs in up to 6.5% of patients. Current international guidelines classify polypectomy as one of the endoscopic procedures with high risk of hemorrhage.

Risk factors for PPB include advanced age, cardiovascular or renal diseases, large polyp size, pedunculated morphology, proximal location in right colon, and the use of antithrombotic medications. Among them, the use of oral anticoagulants such as warfarin and direct oral anticoagulants (DOAC) is associated with a substantially higher risk of PPB up to 13.7%.

While prophylactic clipping is often performed by endoscopists to reduce the PPB risk in clinical practice, the available evidence on its efficacy has been heterogenous and conflicting. A number of studies reported the efficacy of prophylactic clip closure after endoscopic resection to prevent PPB. On the contrary, several randomized trials did not demonstrate any significant benefit of prophylactic clipping. In recent meta-analyses, routine use of prophylactic clipping was not shown to decrease PPB risk, except in a subgroup of colonic lesion larger than 20mm and proximal to the hepatic flexure. However, the proportion of patients on oral anticoagulants was low (5.1%-26%) in the above studies, limiting the generalizability of results to this high-risk patient group. Our preliminary data involving >500 patients on oral anticoagulants showed a lower PPB risk in prophylactic clipping group among DOAC users.

Also, although the consensus is that DOAC users do not require routine drug level monitoring, studies have shown a positive correlation between plasma drug level and bleeding risks. In special circumstances, the measurement of anticoagulant effect would provide management guide, including patients with extreme body weight or renal impairment, imminent need of antidote reversal or before invasive surgical procedures. Diluted thrombin time and anti-factor Xa assays demonstrated a reasonable linear correlation with the plasma drug concentration, yet they are indirect tests. Specific DOAC drug level can be checked to provide direct measurement of anticoagulant effect. In the setting of elective invasive procedures, a pre-operative cutoff level (≦30 ng/mL) for dabigatran and rivaroxaban has been proposed. Patients undergoing interventions with high bleeding risks may benefit from drug level measurement by informing the operators to perform prophylactic measures to reduce hemorrhagic complications.

In this randomized controlled trial, we aim to evaluate the efficacy of prophylactic clipping in preventing PPB in colonoscopy among DOAC users. We also wish to investigate the correlation of pre-endoscopy DOAC drug level and the risk of hemorrhagic complications after the procedure.

• Study Type: Interventional
• Enrollment (Anticipated): 584
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Louis Ho Shing Lau; Phone Number: 35052211; Email: louishslau@cuhk.edu.lhk

Study Locations

• Hong Kong
  • New Territories
    • Shatin, New Territories, Hong Kong
      • Recruiting
      • Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• They are active users of any DOAC
• They require elective colonoscopy for colorectal cancer screening, polyp surveillance, or investigation of symptoms such as anemia or past gastrointestinal bleeding
• Aged 18 years old or above;
• Written informed consent obtained.

Exclusion Criteria:

• Absolute contraindications to colonoscopy
• Any medical conditions precluding interruption of DOAC for procedure
• Any medical conditions requiring concomitant uninterrupted dual antiplatelet drugs (single antiplatelet drug users will not be excluded)
• Active gastrointestinal bleeding
• Clinically significant bleeding tendency (decompensated cirrhosis or severe thrombocytopenia)
• Severe renal impairment (defined as creatinine clearance < 15 ml/min)
• Pregnancy or lactation;
• Advanced comorbid conditions (defined as American Society of Anesthesiologists grade 4 or above)
• Unable to obtain informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intervention group; In the intervention arm, one or more endoclips will be used to completely close the mucosal defect after polypectomy. Prophylactic clipping will be applied to all post-polypectomy sites. The total number of endoclips used will be recorded.	Procedure: Endoclip; In the intervention arm, one or more endoclips will be used to completely close the mucosal defect after polypectomy. Prophylactic clipping will be applied to all post-polypectomy sites. The total number of endoclips used will be recorded.
NO_INTERVENTION: Control group; In the control arm, no endoclip will be applied to all post-polypectomy sites, with the exceptions of uncontrolled immediate PPB or pre-treatment in very large pedunculated polyps as specified above. The subjects with endoclips applied due to safety reasons will be included in the subsequent intention-to-treat analysis, but not the per-protocol analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically significant delayed post-polypectomy bleeding	The primary endpoint is clinically significant delayed post-polypectomy bleeding.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall delayed post-polypectomy bleeding rate and cardio-thrombotic event rate	Secondary endpoints are overall delayed post-polypectomy bleeding rate, cardio-thrombotic event rate within 30 days after procedure and pre-endoscopy DOAC drug levels. Overall delayed post-polypectomy bleeding is defined as occurrence of any gastrointestinal bleeding within 30 days after index colonoscopy (including those not fulfilling the criteria of primary endpoint). Cardio-thrombotic events are defined according to the Antithrombotic Trialists' criteria (non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular cause). [44] The baseline and trough DOAC drug levels measured before colonoscopy would also be analyzed and correlated with clinical bleeding or thrombotic events.	2 years

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 15, 2021
• Primary Completion (ANTICIPATED): December 14, 2024
• Study Completion (ANTICIPATED): December 31, 2024

Study Registration Dates

• First Submitted: September 9, 2021
• First Submitted That Met QC Criteria: December 8, 2021
• First Posted (ACTUAL): December 23, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: 2021.381

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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