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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
290
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).
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).
Aberdeen Royal Infirmary
Aberdeen, Aberdeenshire, United Kingdom
RECRUITINGUniversity Hospital of Wales
Cardiff, Cardiff, United Kingdom
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.
Time frame: Days 2, 4 (+/- 1 day), and 14 (+/- 2 days)
Pain scores
Patient will complete a Numerical Rating Scale.The scale is from 0-10 (0= no pain and 10 = worst pain possible)
Time frame: First 14 Days
Opiate requirements
Recording of daily morphine equivalents by research team
Time frame: First 14 days
Nutritional deficit
Number of days without solid food for first 14 days
Time frame: First 14 days
Decline in serum albumen
Albumen measured via blood samples
Time frame: First 14 days
Rise in neutrophils
Neutrophils measured in blood samples
Time frame: 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
Time frame: First 14 days
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250 ml (500 ml if patient weighs over 100 kg) of 0.9% Sodium Chloride
Royal Cornwall Hospital
Truro, Cornwall, United Kingdom
NOT_YET_RECRUITINGRoyal Devon and Exeter Hospital
Exeter, Devon, United Kingdom
NOT_YET_RECRUITINGUniversity College London Hospital
London, Greater London, United Kingdom
RECRUITINGSt Mary's Hospital
London, Greater London, United Kingdom
SUSPENDEDCharing Cross Hospital
London, Greater London, United Kingdom
SUSPENDEDRoyal Liverpool University Hospital
Liverpool, Merseyside, United Kingdom
RECRUITINGAintree University Hospital
Liverpool, Merseyside, United Kingdom
RECRUITINGWhiston Hospital
Whiston, Merseyside, United Kingdom
RECRUITING...and 3 more locations
Local pancreatic injury
Contrast-enhanced CT scan assessed by a central panel
Time frame: Day 14 +/- 7 days
Revised Atlanta Classification (RAC)
RAC severity classification (mild, moderate or severe)
Time frame: 90 days after admission
Infective complications
Infective complications reported
Time frame: First 90 days
Length of hospital stay
Length of time patient remains within hospital as an inpatient
Time frame: Up to 90 days
Mortality
Patient death
Time frame: Within the first 90 days
Patient reported outcome
EuroQol EQ-5D-5L
Time frame: Day 4, Day 14 and Day 90
Potential safety signals
Adverse events relating to infliximab including infusion reactions and delayed serum sickness reactions
Time frame: Up to 90 days
Anti-infliximab antibody concentration
Blood sample analysis to determine the concentration of anti-infliximab antibodies
Time frame: Day 14
Incremental cost per quality adjusted life years (QALY) gained by trial treatment
QALYs using data from the EQ-5D-5L questionnaire
Time frame: Days 4, 14 and 90
Infliximab concentration
Infliximab measured in blood samples
Time frame: Day 14