No Effect of Methylnaltrexone on Acute Pancreatitis Severity: A Multicenter Randomized Controlled Trial

Cecilie Siggaard Knoph, Mathias Ellgaard Cook, Srdan Novovic, Mark Berner Hansen, Michael Bau Mortensen, Liv Bjerre Juul Nielsen, Irene Maria Høgsberg, Celina Salomon, Celine Emilie Lindqvist Neergaard, Aseel Jabbar Aajwad, Sanjay Pandanaboyana, Lone Schmidt Sørensen, Ole Thorlacius-Ussing, Jens Brøndum Frøkjær, Søren Schou Olesen, Asbjørn Mohr Drewes

Abstract

INTRODUCTION: Opioids used to manage severe pain in acute pancreatitis (AP) might exacerbate the disease through effects on gastrointestinal and immune functions. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, may counteract these effects without changing analgesia.

METHODS: This double-blind, randomized, placebo-controlled trial included adult patients with AP and systemic inflammatory response syndrome at 4 Danish centers. Patients were randomized to receive 5 days of continuous intravenous methylnaltrexone (0.15 mg/kg/d) or placebo added to the standard of care. The primary end point was the Pancreatitis Activity Scoring System score after 48 hours of treatment. Main secondary outcomes included pain scores, opioid use, disease severity, and mortality.

RESULTS: In total, 105 patients (54% men) were randomized to methylnaltrexone (n = 51) or placebo (n = 54). After 48 hours, the Pancreatitis Activity Scoring System score was 134.3 points in the methylnaltrexone group and 130.5 points in the placebo group (difference 3.8, 95% confidence interval [CI] -40.1 to 47.6; P = 0.87). At 48 hours, we found no differences between the groups in pain severity (0.0, 95% CI -0.8 to 0.9; P = 0.94), pain interference (-0.3, 95% CI -1.4 to 0.8; P = 0.55), and morphine equivalent doses (6.5 mg, 95% CI -2.1 to 15.2; P = 0.14). Methylnaltrexone also did not affect the risk of severe disease (8%, 95% CI -11 to 28; P = 0.38) and mortality (6%, 95% CI -1 to 12; P = 0.11). The medication was well tolerated.

DISCUSSION: Methylnaltrexone treatment did not achieve superiority over placebo for reducing the severity of AP.

OriginalsprogEngelsk
TidsskriftThe American journal of gastroenterology
Vol/bind119
Udgave nummer11
Sider (fra-til)2307-16
Antal sider10
ISSN0002-9270
DOI
StatusE-pub ahead of print - 25 jun. 2024

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