Randomised Treatment of Acute Pancreatitis With Infliximab: Double-blind Multi-centre Trial (RAPID-I)
Randomised Treatment of Acute Pancreatitis With Infliximab: Double-blind Multi-centre Trial (RAPID-I)
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.
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.
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 the onset of
 abdominal pain 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

 -  Onset of abdominal pain over 24 h before admission

 -  Previous AP 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

 -  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.