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.

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.