Phase IIb, randomised, double-blind, placebo-controlled, multi-centre trial of infliximab with transcriptomic biomarker and mechanism evaluation in patients with acute pancreatitis
Acute pancreatitis
Current interventions: Participants will be randomised using an online web randomisation system, by a delegated member of the research team to receive a single, 2-hour infusion of either: Arm A: 5 mg/kg infliximab Arm B: 10 mg/kg infliximab (Following the recommendation of the Independent Data and Safety Monitoring Committee, the 10 mg/kg infliximab arm was stopped on 19/05/2026 owing to a lack of efficacy) Arm C: placebo (0.9% sodium chloride) Participants will be randomised to treatment allocations in a ratio of 1:1:1, stratified by individual research sites. Patients will only receive a single, 2-hour infusion of their treatment allocation. Infliximab is given within half a day of a patient arriving in hospital, much earlier than with other drugs tested in acute pancreatitis. Whilst the patient is in hospital, information will be recorded and blood samples will be taken. Patients will be followed up until Day 90 (Day 1 beginning from when the patient receives the trial infusion). Previous interventions: Participants will be randomised using an online web randomisation system, by a delegated member of the research team to receive a single, 2-hour infusion of either: Arm A: 5 mg/kg infliximab Arm B: 10 mg/kg infliximab Arm C: placebo (0.9% sodium chloride) Participants will be randomised to treatment allocations in a ratio of 1:1:1, stratified by individual research sites. Patients will only receive a single, 2-hour infusion of their treatment allocation. Infliximab is given within half a day of a patient arriving in hospital, much earlier than with other drugs tested in acute pancreatitis. Whilst the patient is in hospital, information will be recorded and blood samples will be taken. Patients will be followed up until Day 90 (Day 1 beginning from when the patient receives the trial infusion).
Current participant inclusion criteria as of 01/07/2026: 1. Adult patients attending A&E at or admitted to recruiting hospitals via a General Practitioner with a new diagnosis of AP established by two of: 1.1. Typical continuous upper abdominal pain 1.2. Amylase and/or lipase three or more times the upper limit of normal 1.3. Characteristic findings on abdominal imaging (if undertaken urgently by CT or magnetic resonance imaging, MRI);↲ and 2) Patients in whom trial treatment can be started as soon as possible and within 36 hours of admission, allowing 120 min within the 36-hour period for preparation of trial medication; and 3) Patients from whom appropriate consent is obtained (consent to be given by the patient or their legal representative). Previous participant inclusion criteria as of 14/08/2018: 1. Adult patients attending A&E at or admitted to recruiting hospitals via a general practitioner with a new diagnosis of AP established by two of: 1.1. Typical continuous upper abdominal pain 1.2. Amylase and/or lipase three or more times the upper limit of normal; 1.3. Characteristic findings on abdominal imaging (if undertaken urgently by CT or magnetic resonance imaging, MRI); 2. Patients in whom trial treatment can be started within 12 hours of recorded admission and allowing 120 min for pharmacy to prepare trial medication 3. Patients from whom appropriate consent is obtained (consent to be given by the patient or their legal representative). Previous participant inclusion criteria: 1. Adult patients attending A&E at recruiting centres from whom appropriate consent is obtained (consent to be given by the patient or their legal representative) 2. Patients in whom trial treatment can be started within 12 hours of admission (allowing 120 min for Pharmacy to prepare trial medication) 3. A new diagnosis of AP (all severity levels) as established by two of: 3.1. Typical continuous upper abdominal pain 3.2. Amylase and/or lipase three or more times the upper limi
Current exclusion criteria as of 01/07/2026: 1. Age <18 or >85 2. Patients with a body weight of over 200 kilograms 3. Known previous AP diagnosed within the last 30 days or known chronic pancreatitis 4. Known multiple sclerosis, systemic vasculitis, Guillain-Barré syndrome or other demyelinating disorder 5. Known epilepsy 6. Moderate to severe heart failure and/or coronary heart disease (New York Heart Association (NYHA) Functional Class III/IV) 7. Known severe respiratory conditions, including cystic fibrosis, severe asthma and severe chronic obstructive pulmonary disease (COPD), on home oxygen or home mechanical ventilation 8. Jaundice (serum bilirubin >50 µmol/L), and/or known advanced liver disease, on waiting list for liver transplantation or considered unsuitable for transplantation 9. Known cancer for which chemotherapy and/or radiotherapy is ongoing or was completed within less than 6 months from admission 10. Known haematological malignancy 11. Known cancer that is end-stage with ongoing palliative care or for which palliative care is appropriate 12. Known established infection prior to or suspected infection, including COVID-19§, at the time of AP onset 13. Known history of (including that identified on chest x-ray) or household contact with individuals who have tuberculosis or opportunistic infection 14. Known history of infective hepatitis (unless recovered from previous hepatitis A) 15. Known rare diseases or inborn errors of metabolism that significantly increase the risk of infections, including severe combined immunodeficiency (SCID) and homozygous sickle cell disease 16. Known immunosuppressive or biologic therapy within one month of admission 17. Known live vaccines or therapeutic infectious agents within one month of admission 18. Known hypersensitivity to infliximab or to inactive components of infliximab or to any murine proteins 19. Known pregnancy or lactation at the time of admission 20. Women of childbearing potential who do not agree to u