Acute pancreatitis (AP) is a growing cause of morbidity and mortality for which there is no licensed disease-modifying pharmacotherapy. Tumour necrosis factor alpha (TNF-α) has been implicated in the inflammatory cascade of AP. On this mechanistic basis, neutralising TNF-α with the monoclonal antibody infliximab could modify systemic and local inflammatory responses and thereby improve clinical outcomes. The RAPID-I trial is designed to evaluate the efficacy, safety, cost-effectiveness and mechanism of action of infliximab in hospitalised patients with AP.
RAPID-I is a phase 2b, double-blind, placebo-controlled, multi-centre randomised trial. The planned sample size is 240 participants. Eligible patients with AP will be randomised in a 1:1:1 ratio to receive a single intravenous infusion of either 5 mg/kg infliximab, 10 mg/kg infliximab, or matched placebo. Treatment must be initiated within 36 hours of hospital admission. The protocol specifies outcome assessments at early time points and at day 14 and day 90 to capture both acute inflammation and recovery.
Participants will receive a single weight-based infusion of infliximab at one of two dose levels (5 mg/kg or 10 mg/kg) or placebo, with allocation concealed and investigators, participants, and outcome assessors blinded to treatment assignment. Randomisation is in equal thirds (1:1:1). The trial focuses on early intervention, with the infusion required within 36 hours of admission to address the early inflammatory phase of AP.
The primary outcome is mean serum C-reactive protein (CRP) measured on trial days 2, 4 (±1 day) and 14 (±2 days), summarised as the area under the curve (AUC) across these time points. A reduction of 25% in the CRP AUC in either active infliximab arm compared with placebo is pre-specified as clinically meaningful. Using CRP AUC as the primary endpoint targets systemic inflammation as a marker of disease activity and potential treatment effect.
Secondary outcome measures are broad and encompass symptom burden, organ dysfunction, local pancreatic injury, infections, resource use, and patient-reported health. They include:
These secondary endpoints aim to characterise clinical benefit, complications, and recovery trajectory beyond systemic inflammation.
Potential safety signals will be adverse events related to infliximab administration. The protocol includes monitoring for such events. In parallel with clinical outcomes, mechanistic studies will measure transcriptomic signatures, cytokine concentrations and leukocyte profiles at baseline and at the same time points used for CRP. These biomarker assessments are intended to clarify the immunological effects of infliximab in AP and to explore potential predictors of response or harm.
The trial incorporates two planned adaptive interim analyses. Details of adaptation rules, stopping criteria, or statistical thresholds were specified in the full protocol; the summary reports only that two adaptive analyses are planned. The primary analysis compares CRP AUC between each active infliximab arm and placebo, with a 25% reduction considered clinically meaningful. Secondary analyses will examine the range of clinical, imaging, laboratory and patient-reported endpoints.
Cost-effectiveness will be evaluated over a 90-day (±7 days) time horizon. The economic analysis will combine healthcare costs incurred during follow-up with quality-adjusted life years (QALYs) to estimate cost per QALY for infliximab versus placebo. This assessment is intended to inform whether any clinical benefits translate into value for healthcare systems.
The protocol has Research Ethics Committee approval from South Central - Oxford C Research Ethics Committee (reference 18/SC/0262). The trial is registered with ClinicalTrials.gov under number NCT03684278. The investigators plan dissemination of findings via peer-reviewed publication and presentation at national and international conferences and meetings.
Note: This summary reflects the details provided in the trial protocol abstract. Specific operational details, statistical plans, eligibility criteria and full safety monitoring procedures are described in the full protocol but are not reported in the source abstract.