Racecadotril Versus Loperamide in Acute Radiation Enteritis: A Randomized, Double-Masked, Phase 3, Noninferiority Trial

Int J Radiat Oncol Biol Phys. 2024 Mar 1;118(3):616-625. doi: 10.1016/j.ijrobp.2023.09.021. Epub 2023 Sep 22.

Abstract

Purpose: There is currently no gold standard for the management of acute radiation enteritis. We compared the efficacy and safety of Racecadotril, an anti-hypersecretory drug, versus Loperamide, an anti-motility agent, in acute radiation enteritis.

Methods and materials: We conducted a randomized, double-masked, non-inferiority trial at a single research institute. Patients receiving curative radiation for pelvic malignancies, who developed grade 2 or 3 diarrhea (as per Common Terminology Criteria for Adverse Events, v 4.0) were included in the study. Patients in the intervention arm received Racecadotril and placebo. Patients in the control arm received Loperamide and placebo. The primary outcome was the resolution of diarrhea, 48 hours after the start of treatment.

Results: 162 patients were randomized between 2019 and 2022. On intention-to-treat analysis, 68/81 patients, 84%, (95% CI, 74.1%-91.2%) in the Racecadotril arm and 70/81, 86.4%, (95% CI, 77.0%-93.0%) in the Loperamide arm improved from grade 2 or 3 diarrhea to grade 1 or 0, (P= .66, χ2 test). The difference in proportion was 2.4% (95% CI: -8.5% to 13.4%). Since the upper boundary of the 95% CI crossed our non-inferiority margin of 10% (13.4%) we could not prove the non-inferiority of Racecadotril over Loperamide. Rebound constipation was more in the Loperamide arm compared to Racecadotril (17.3% vs 6.2%; P = .028) CONCLUSIONS: The non-inferiority of Racecadotril to Loperamide in acute radiation enteritis could not be demonstrated. However, Racecadotril can be the preferred drug of choice in acute radiation enteritis because Racecadotril does not affect bowel motility, achieved a high clinical success rate similar to that of Loperamide, and was associated with lesser side effects.

Publication types

  • Clinical Trial, Phase III
  • Equivalence Trial
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Acute Radiation Syndrome* / drug therapy
  • Antidiarrheals / adverse effects
  • Diarrhea / drug therapy
  • Diarrhea / etiology
  • Double-Blind Method
  • Enteritis* / chemically induced
  • Enteritis* / etiology
  • Humans
  • Loperamide / adverse effects
  • Thiorphan* / analogs & derivatives

Substances

  • Antidiarrheals
  • Loperamide
  • racecadotril
  • Thiorphan