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

University of Liverpool

Status and phase: Enrolling; Phase 2

Conditions: Acute Pancreatitis

Treatments: Drug: Infusion of 10 mg/kg Infliximab; Other: 0.9% Sodium Chloride (Placebo); Drug: Infusion of 5 mg/kg Infliximab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03684278

UoL001326

2017-003840-19 (EudraCT Number)

15/20/01 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 290 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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290 participants in 3 patient groups, including a placebo group

Infusion of 5 mg/kg Infliximab

Active Comparator group

Description:

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.

Treatment:

Drug: Infusion of 5 mg/kg Infliximab

Infusion of 10 mg/kg Infliximab

Active Comparator group

Description:

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.

Treatment:

Drug: Infusion of 10 mg/kg Infliximab

0.9% Sodium Chloride (Placebo)

Placebo Comparator group

Description:

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.

Treatment:

Other: 0.9% Sodium Chloride (Placebo)