A peptide-first hemostatic strategy for oozing-type postsphincterotomy bleeding during endoscopic retrograde cholangiopancreatography: a multicenter noninferiority randomized controlled trial (PROTECT-EST).

BACKGROUND AND AIMS: Immediate bleeding after endoscopic sphincterotomy (EST) is a common adverse event during ERCP. However, the optimal first-line hemostatic strategy remains undefined because comparative randomized trials are lacking. We aimed to evaluate the noninferiority of a self-assembling peptide (SAP)-first strategy compared with conventional balloon tamponade for oozing-type immediate post-EST bleeding, with superiority testing performed as a prespecified exploratory analysis.

METHODS

PROTECT-EST (A peptide-first hemostatic strategy for oozing-type postsphincterotomy bleeding during endoscopic retrograde cholangiopancreatography: a multicenter noninferiority randomized controlled trial) was a multicenter, investigator-initiated, parallel-group randomized controlled trial conducted at tertiary referral centers in Japan. Adults with oozing-type bleeding persisting for ≥180 seconds after EST without spontaneous hemostasis were randomly assigned (1:1) to SAP application or balloon tamponade as the initial hemostatic strategy. The primary end point was successful initial hemostasis, defined as the absence of active oozing for ≥3 minutes after the assigned intervention. Noninferiority was tested first, and superiority was assessed as a prespecified exploratory analysis.

RESULTS

A total of 130 patients were randomized (SAP group, n = 65; balloon group, n = 65). SAP met the prespecified noninferiority criterion. In the prespecified exploratory superiority analysis, successful initial hemostasis occurred in 60 of 65 patients (92.3%) in the SAP group and 50 of 65 patients (76.9%) in the balloon group (risk difference, 15.4 percentage points; 95% CI, 3.1-27.7; P = .027). The mean time to completion of the initial hemostatic intervention was shorter in the SAP group, and rescue hemostatic devices were required less frequently (7.7% vs 23.1%; P = .033). Adverse events and delayed hemorrhage were similar between groups. In supportive bootstrap-based economic analyses, the SAP-first strategy was generally more effective and not more costly.

CONCLUSIONS

In this noninferiority trial, a SAP-first strategy was noninferior to balloon tamponade for oozing-type immediate post-EST bleeding and, in exploratory analyses, was associated with higher initial hemostasis, shorter procedure time, and less rescue device use. SAP may represent a practical first-line option, although external validation is warranted.