Randomised treatment of acute pancreatitis with infliximab: protocol for a double-blind, placebo-controlled, multi-centre, adaptive, phase 2 superiority trial (RAPID-I)
TL;DR
The efficacy, safety, cost-effectiveness and mechanism of action of the anti-TNF antibody infliximab in patients with AP is tested and potential safety signals will be adverse events related to infliximab.
Abstract
Abstract Introduction Acute pancreatitis (AP) is an increasingly common cause of substantial morbidity and risk of mortality without licensed specific drug therapy. Because tumour necrosis factor α (TNF-α) contributes to AP, anti-TNF therapy may improve outcome from AP. This trial aims to test the efficacy, safety, cost-effectiveness and mechanism of action of the anti-TNF antibody infliximab in patients with AP. Methods and analysis Randomised treatment of Acute Pancreatitis with Infliximab: Double-blind, placebo-controlled, multi-centre trial (RAPID-I) is a phase 2b trial designed to randomise 240 patients with AP to receive a single 5 mg/kg or 10 mg/kg infliximab or placebo infusion in a 1:1:1 ratio, initiated within 36 hours of hospital admission. The primary outcome is mean serum C-reactive protein (CRP) on trial days 2, 4 (±1 day) and 14 (±2 days) summated as area under the curve (AUC), with 25% reduction in either active arm compared with placebo considered clinically meaningful. Secondary outcomes include cumulative pain scores, opiate requirements, nutritional deficit (days without solid food), decline in serum albumin (negative AUC), rise in neutrophils (AUC), cumulative selective serial organ failure assessment (SOFA-2) scores, local pancreatic injury on contrast-enhanced CT scan (CECT day 14±7 days), infections, length of stay, mortality and patient reported outcome on days 4 (±1 day), 14 (±2 days) and 90 (±7 days). Cost-effectiveness will be based on costs and quality-adjusted life years over 90 (±7) days. Potential safety signals will be adverse events related to infliximab. Transcriptomic, cytokine and leucocyte profiles will be assessed at baseline and the same time points as CRP. Two adaptive interim analyses are planned. Ethics and dissemination The protocol has received Research Ethics Committee approval (South Central – Oxford C Research Ethics Committee 18/SC/0262). The findings will be disseminated through peer reviewed publication, national and international conferences and meetings. Trial registration number NCT03684278.