Randomised Treatment of Acute Pancreatitis With Infliximab: Double-blind, Placebo-controlled, Multi-centre Trial (RAPID-I) (RAPID-I)

Phase IIb, Randomised, Double-blind, Placebo-controlled, Multi-centre Trial of Infliximab With Transcriptomic Biomarker and Mechanism Evaluation in Patients With Acute Pancreatitis.

This study evaluates the effectiveness and safety of infliximab in the treatment of acute pancreatitis in adults. A third of participants will receive one single dose of infliximab via infusion, another third will receive a higher dose of infliximab via infusion and the final third of participants will receive a placebo infusion.

Study Overview

• Status: Recruiting
• Conditions: Acute Pancreatitis
• Intervention / Treatment: Drug: Infusion of 5 mg/kg Infliximab; Drug: Infusion of 10 mg/kg Infliximab; Other: 0.9% Sodium Chloride (Placebo)

Detailed Description

Acute pancreatitis (AP) is an inflammatory disorder of the pancreas causing excruciating pain, gastrointestinal dysfunction and pronounced systemic inflammatory responses with circulatory and respiratory disturbances that can lead to organ failure and death.

Tumour necrosis factor alpha (TNFα) has a major role in the pathogenesis and severity of acute pancreatitis. TNFα levels rise early and remain elevated for days in human AP, proportional to severity, presenting a suitable drug target to inhibit the amplified immune responses that further damage the pancreas and drive widespread organ dysfunction.

Infliximab is a chimeric monoclonal antibody biologic drug that blocks the actions of tumor necrosis factor alpha (TNF-α) and is normally used to treat autoimmune diseases. Infliximab has been selected as it is given via intravenous infusion, which will ensure rapid bioavailability to treat AP. This is different from most other biologics, which are given subcutaneously.

This trial will determine the efficacy of early initiation of anti-TNF treatment in AP, setting new standards for trials in AP. Using a randomised, double-blind, placebo-controlled adaptive design, with two doses of a single intravenous infusion of infliximab at 5 mg/kg or 10 mg/kg, the trial will determine size of any effect and safety of this treatment.

• Study Type: Interventional
• Enrollment (Estimated): 290
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Matt Smyth, BSc; Phone Number: (0) 151 794 9774; Email: rapid.one@liverpool.ac.uk
• Study Contact Backup: Name: Catherine E Spowart, BSc; Phone Number: (0) 151 794 9776; Email: catherine.spowart@liverpool.ac.uk

Study Locations

• United Kingdom
  • Aberdeenshire
    • Aberdeen, Aberdeenshire, United Kingdom, AB25 2ZN
      • Recruiting
      • Aberdeen Royal Infirmary
      • Contact: Jamie Cooper, MD; Email: jamie.cooper2@nhs.scot
  • Cardiff
    • Cardiff, Cardiff, United Kingdom, CF14 4XW
      • Not yet recruiting
      • University Hospital of Wales
      • Contact: David O'Reilly, MD, FRCS; Email: David.O'reilly@wales.nhs.uk
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Not yet recruiting
      • Royal Cornwall Hospital
      • Contact: James Clark, MD, FRCS; Email: james.clark10@nhs.net
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Not yet recruiting
      • Royal Devon and Exeter Hospital
      • Contact: Antonio Manzelli, MD, BSc, PhD; Email: antonio.manzelli@nhs.net
  • Greater London
    • London, Greater London, United Kingdom, NW1 2BU
      • Recruiting
      • University College London Hospital
      • Contact: Samer Elkhodair, MD; Email: samer.elkhodair@nhs.net
    • London, Greater London, United Kingdom, W2 1NY
      • Suspended
      • St Mary's Hospital
    • London, Greater London, United Kingdom, W6 8RF
      • Suspended
      • Charing Cross Hospital
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L7 8XP
      • Recruiting
      • Royal Liverpool University Hospital
      • Contact: Robert Sutton, DPhil, FRCS; Email: r.sutton@liverpool.ac.uk
    • Liverpool, Merseyside, United Kingdom, L9 7AL
      • Recruiting
      • Aintree University Hospital
      • Contact: Rajarshi Mukherjee, MB, BChir, FRCS (Gen), PhD; Email: rishim@liverpool.ac.uk
    • Whiston, Merseyside, United Kingdom, L35 5DR
      • Recruiting
      • Whiston Hospital
      • Contact: Sunjay Kanwar, MB, BS, MD; Email: Sunjay.Kanwar@sthk.nhs.uk
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • Recruiting
      • Queen's Medical Centre
      • Contact: Dileep Lobo, MB, BS, DM, FRCS; Email: Dileep.Lobo@nottingham.ac.uk
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Recruiting
      • John Radcliffe Hospital
      • Contact: Giles Bond-Smith, MB, BS, BSc, FRCS; Email: Giles.Bond-smith@ouh.nhs.uk
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF
      • Not yet recruiting
      • St James's University Hospital
      • Contact: Andrew M Smith, MB, BS, MD, FRCS; Email: andrewmsmith@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients attending Accident and Emergency (A&E) at or admitted to recruiting hospitals via a GP with a new diagnosis of AP established by two of the following three criteria: (1) typical continuous upper abdominal pain; (2) amylase and/or lipase three or more times the upper limit of normal; (3) characteristic findings on abdominal imaging (if undertaken urgently by CT or MRI)
• Patients in whom trial treatment can be started within 36 hours of admission to hospital with a new diagnosis of acute pancreatitis allowing 120 min for preparation of trial medication
• Patients from whom appropriate consent is obtained (from the patient or their legal representative).

Exclusion Criteria:

• Age <18 or >85
• Patients with a bodyweight over 200 kg
• Known previous AP within the last 30 days or chronic pancreatitis
• Multiple sclerosis, systemic vasculitis, Guillain-Barré syndrome or other demyelinating disorder
• Known epilepsy
• Moderate to severe heart failure and/or coronary disease (NYHA III/IV)
• Severe respiratory conditions including cystic fibrosis, severe asthma and severe chronic obstructive pulmonary disease (COPD)
• On home oxygen or home mechanical ventilation
• Jaundice and/or known advanced liver disease
• Known cancer for which chemotherapy and/or radiotherapy ongoing/completed in last 6 months
• Known haematological malignancy
• Known cancer with palliative care
• Known established infection prior to or suspected infection, including COVID-19, at the time of AP onset
• Known history of tuberculosis, or household contact with those with tuberculosis or opportunistic infection
• Known history of infective hepatitis
• Rare diseases or inborn errors of metabolism that significantly increase the risk of infections, including severe combined immunodeficiency (SCID) and homozygous sickle cell disease
• Known live vaccine or infectious agent within one month of admission
• Known immunosuppressive or biologic therapy within one month of admission
• Known hypersensitivity to infliximab or to inactive components of REMICADE® or to any murine proteins
• Known pregnancy or lactation at admission
• Females of childbearing potential who do not agree to use adequate contraception up to 6 months after infliximab infusion
• Known participation in investigational medicinal product study within last three months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Infusion of 5 mg/kg Infliximab; Infliximab (Remicade) to be administered as a one time intravenous infusion in 250 ml (500 ml if patient weighs over 100 kg) 0.9% sodium chloride solution over a period of 2 hours. Dosage calculated at 5 mg of Infliximab, per kg of patient body weight.	Drug: Infusion of 5 mg/kg Infliximab; Infliximab is a prescription drug with marketing authorisation for the treatment of rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis and psoriasis. In the RAPID-I trial infliximab will be used outside the manufacturer's indication for the treatment of AP, and it is classed as an investigational medicinal product (IMP).; Other Names: Remicade
Active Comparator: Infusion of 10 mg/kg Infliximab; Infliximab (Remicade) to be administered as a one time intravenous infusion in 250 ml (500 ml if patient weighs over 100 kg) 0.9% sodium chloride solution over a period of 2 hours. Dosage calculated at 10 mg of Infliximab, per kg of patient body weight.	Drug: Infusion of 10 mg/kg Infliximab; Infliximab is a prescription drug with marketing authorisation for the treatment of rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis and psoriasis. In the RAPID-I trial infliximab will be used outside the manufacturer's indication for the treatment of AP, and it is classed as an investigational medicinal product (IMP).; Other Names: Remicade
Placebo Comparator: 0.9% Sodium Chloride (Placebo); 250 ml (500 ml if patient weighs over 100 kg) 0.9% Sodium Chloride to be administered as a one time intravenous infusion over a period of 2 hours.	Other: 0.9% Sodium Chloride (Placebo); 250 ml (500 ml if patient weighs over 100 kg) of 0.9% Sodium Chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in mean serum CRP measured on days 2, 4 and 14	Difference in mean serum CRP measured on (summated as AUC) in the active arms (5 mg/kg or 10 mg/kg) versus the placebo arm. CRP assays will be undertaken on blood samples centrally to ensure standardised measurement, and when central measurements of CRP at specific time points are not available for any patient, CRP measures from that patient's specific recruiting centre will be sought.	Days 2, 4 (+/- 1 day), and 14 (+/- 2 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Revised Atlanta Classification (RAC)	RAC severity classification (mild, moderate or severe)	90 days after admission
Infective complications	Infective complications reported	First 90 days
Length of hospital stay	Length of time patient remains within hospital as an inpatient	Up to 90 days
Mortality	Patient death	Within the first 90 days
Potential safety signals	Adverse events relating to infliximab including infusion reactions and delayed serum sickness reactions	Up to 90 days
Pain scores	Patient will complete a Numerical Rating Scale.The scale is from 0-10 (0= no pain and 10 = worst pain possible)	First 14 Days
Opiate requirements	Recording of daily morphine equivalents by research team	First 14 days
Nutritional deficit	Number of days without solid food for first 14 days	First 14 days
Decline in serum albumen	Albumen measured via blood samples	First 14 days
Rise in neutrophils	Neutrophils measured in blood samples	First 14 days
Sequential organ failure assessment (SOFA) score	Summed respiratory (0-4), cardiovascular (0-4) and renal (0-4) SOFA scores on each of the first 28 days after hospital admission	First 14 days
Local pancreatic injury	Contrast-enhanced CT scan assessed by a central panel	Day 14 +/- 7 days
Patient reported outcome	EuroQol EQ-5D-5L	Day 4, Day 14 and Day 90
Anti-infliximab antibody concentration	Blood sample analysis to determine the concentration of anti-infliximab antibodies	Day 14
Incremental cost per quality adjusted life years (QALY) gained by trial treatment	QALYs using data from the EQ-5D-5L questionnaire	Days 4, 14 and 90
Infliximab concentration	Infliximab measured in blood samples	Day 14

Collaborators and Investigators

• Sponsor: University of Liverpool
• Collaborators: Merck Sharp & Dohme LLC; Medical Research Council; Liverpool University Hospitals NHS Foundation Trust; National Institute for Health Research, United Kingdom; Bangor University
• Investigators: Principal Investigator: Robert Sutton, DPhil, FRCS, University of Liverpool

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: July 4, 2018
• First Submitted That Met QC Criteria: September 24, 2018
• First Posted (Actual): September 25, 2018

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Amino Acids, Peptides, and Proteins; Proteins; Substandard Drugs; Pharmaceutical Preparations; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Infliximab; Counterfeit Drugs; Sodium Chloride
• Other Study ID Numbers: UoL001326; 2017-003840-19 (EudraCT Number); 15/20/01 (Other Grant/Funding Number: MRC and NIHR EME)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No