Randomized Controlled Trial of Over-the-Scope Clip as Initial Treatment of Severe Nonvariceal Upper Gastrointestinal Bleeding

Abstract

Background and aims: No prior randomized controlled trial (RCT) has reported patient outcomes of large over-the-scope clip (OTSC) compared to standard hemostasis as initial endoscopic treatment of severe NVUGIB. This was our study aim.

Methods: Patients with bleeding ulcers or Dieulafoy's lesions and major stigmata of hemorrhage - SRH (active spurting bleeding, visible vessel, or clot) - or lesser SRH (oozing bleeding or flat spots - with arterial blood flow by Doppler probe) were randomized to OTSC or standard endoscopic hemostasis (with hemoclips or multipolar electrocoagulation - MPEC). Patients and their healthcare providers were blinded to treatments and made all post-randomization management decisions. Ulcer patients received high dose intravenous infusions of proton pump inhibitors (PPI) for 3 days, then 27 days of oral PPI. 30 day outcomes were prospectively recorded; data management was with SAS; and data analysis was by a statistician.

Results: 53 patients (25 OTSC, 28 Standard) were randomized, with similar baseline risk factors. However, there were significant differences in OTSC vs. Standard groups in rates of rebleeding (4% vs. 28.6%; p = .017; relative risk 0.10, 95% confidence intervals 0.01, 0.91; number needed to treat 4); severe complications (0 % vs. 14.3%); and post-randomization units of red cell transfusions (0.04 vs. 0.68). All rebleeds occurred in patients with major SRH and none with lesser SRH.

Conclusion: 1. OTSC significantly reduced rates of rebleeding, severe complications, and post-randomization red cell transfusions. 2. Patients with major stigmata benefited significantly from hemostasis with OTSC, but those with lesser stigmata did not. (ClinicalTrials.gov, Number: NCT03065465).

Keywords: Dieulafoy’s Lesion; Hemoclips; Nonvariceal UGI Hemorrhage; Ulcer Bleeding.

Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.. Proportion of All Patients (with Ulcers or Dieulafoy’s Lesions) Without Further Bleeding (Rebleed Free) During 30 Days After Randomization

All 53 patients are included – 25 OTSC and 28 Standard hemostasis. This is a Kaplan-Meier plot of time to further bleeding, with log rank test p = 0.016. The cumulative further bleeding rate to 30 days was 4.0% (1/25) in the OTSC group vs. 28.6% (8/28) in the Standard treatment group. The number needed to treat is 4.0.

Figure 2.. Proportion of Peptic Ulcer Patients without Further Bleeding (Rebleed free) During 30 Days of Follow-up After Randomization.

This is a Kaplan-Meier plot of time to further bleeding, with log rank test p = 0.026. The cumulative 30-day further bleeding rate was 4.3% (1/23) in the OTSC group vs. 28% (7/25) in the Standard hemostasis group. The NNT is 4.2.

Figure 3.. Proportion of Patients with Major Stigmata of Hemorrhage (SRH) without Further Bleeding (Rebleed Free) During 30 Days After Randomization

Legend: Proportion of patients with major stigmata of hemorrhage (active arterial bleeding, non-bleeding visible vessel, or adherent clot) without further bleeding during 30 days after randomization. There are 17 OTSCand 23 Standard treatment patients with these SRH. This is a Kaplan-Meier plot of time to further bleeding of these high risk patients. By log rank test, p = 0.029. The cumulative further bleeding rate was 5.9% (1/17) in the OTSC group vs. 34.8% (8/23) in the Standard treatment group. The number needed to treat is 3.S.