A randomized phase 2 study of the 5-HT4 receptor agonist felcisetrag for postoperative gastrointestinal dysfunction after bowel surgery

Am J Surg. 2024 Aug:234:162-171. doi: 10.1016/j.amjsurg.2024.04.030. Epub 2024 Apr 27.

Abstract

Background: Felcisetrag (5-hydroxytryptamine-4 receptor [5-HT4] agonist) is under investigation as prophylaxis or active treatment for accelerating resolution of gastrointestinal function post-surgery.

Methods: Phase 2, randomized, placebo-controlled, parallel five-arm, double-blind, multicenter study (NCT03827655) in 209 adults undergoing open or laparoscopic-assisted bowel surgery. Patients received intravenous placebo, felcisetrag 0.1 mg/100 ​mL or 0.5 mg/100 ​mL pre-surgery only, or pre-surgery and daily post-surgery until return of gastrointestinal function or for up to 10 days.

Primary endpoint: time to recovery of gastrointestinal function.

Results: Median time to recovery of gastrointestinal function was 2.6 days for both felcisetrag 0.5 ​mg daily and 0.5 ​mg pre-surgery versus 1.9 days for placebo (p ​> ​0.05). There were no notable differences in adverse events between treatment arms.

Conclusions: Felcisetrag was well tolerated with no new safety concerns. However, no clinically meaningful difference in time to recovery of gastrointestinal function versus placebo was observed. Further investigation of the utility of 5-HT4 agonists in complicated, open abdominal surgeries may be warranted.

Keywords: 5-HT(4) agonist; Clinical trial; Postoperative complications; Postoperative gastrointestinal dysfunction; Postoperative ileus.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Digestive System Surgical Procedures / adverse effects
  • Double-Blind Method
  • Female
  • Gastrointestinal Diseases / surgery
  • Humans
  • Laparoscopy / adverse effects
  • Male
  • Middle Aged
  • Postoperative Complications* / prevention & control
  • Recovery of Function / drug effects
  • Serotonin 5-HT4 Receptor Agonists* / therapeutic use
  • Treatment Outcome

Substances

  • Serotonin 5-HT4 Receptor Agonists