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

Официальное название

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

Обзор

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.

Подробное описание

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 higher dose arm was dropped on 19th May 2026, see Study Design), the trial will determine size of any effect and safety of this treatment.

Вмешательства

• Препарат 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).
• Препарат 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).
• Другое 0.9% Sodium Chloride (Placebo)
  250 ml (500 ml if patient weighs over 100 kg) of 0.9% Sodium Chloride

Первичные конечные точки

• Difference in mean serum CRP measured on days 2, 4 and 14 [Срок оценки: Days 2, 4 (+/- 1 day), and 14 (+/- 2 days)]

Вторичные конечные точки (12)

• Pain scores [Срок оценки: First 14 Days]
• Opiate requirements [Срок оценки: First 14 days]
• Nutritional deficit [Срок оценки: First 14 days]
• Decline in serum albumen [Срок оценки: First 14 days]
• Rise in neutrophils [Срок оценки: First 14 days]
• Sequential organ failure assessment (SOFA) score [Срок оценки: First 14 days]
• Local pancreatic injury [Срок оценки: Day 14 +/- 7 days]
• Revised Atlanta Classification (RAC) [Срок оценки: 90 days after admission]
• Infective complications [Срок оценки: First 90 days]
• Length of hospital stay [Срок оценки: Up to 90 days]
• Mortality [Срок оценки: Within the first 90 days]
• Patient reported outcome [Срок оценки: Day 4, Day 14 and Day 90]

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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 (serum bilirubin >50 µmol/L), and/or known advanced liver disease, on waiting list for liver transplantation or considered unsuitable for transplantation
• Known cancer for which chemotherapy and/or radiotherapy ongoing/completed in last 6 months
• Known haematological malignancy
• Known end-stage cancer requiring 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Великобритания · 14 центров

• Aberdeen Royal Infirmary — Aberdeen
• University Hospital of Wales — Cardiff
• Royal Cornwall Hospital — Truro
• Royal Devon and Exeter Hospital — Exeter
• University College London Hospital — London
• St Mary's Hospital — London
• Charing Cross Hospital — London
• Royal Liverpool University Hospital — Liverpool
• … и ещё 6 центров

Идентификаторы

NCT: NCT03684278 · UoL001326 · 2017-003840-19 · 15/20/01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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