A Trial of Indomethacin in Acute Pancreatitis

A Randomized Controlled Trial of Indomethacin in Acute Pancreatitis- Effectiveness and Safety

Acute pancreatitis (AP) is an inflammatory condition of the pancreas following the activated pancreatic enzymes induced by varied causes, with or without other organ(s) dysfunction. The production and release of inflammatory factors is generally considered as the key factor of pathogenesis. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly applied agents for inflammatory diseases. A series studies have proved that indomethacin can reduce the risk of post-endoscopic retrograde cholangiopancreatography (ERCP), but high-quality evidence is still lacking in the field of effectiveness of NSAIDs to treat, rather than prevent, other types of AP. Majority of animal experiments showed that NSAIDs had protective effects for organ functions, but the results of several preliminary clinical studies were inconsistent. Randomized controlled trials are eagerly awaited to elucidate its effects on AP.

Study Overview

• Status: Unknown
• Conditions: Complication; Acute Pancreatitis
• Intervention / Treatment: Drug: Indomethacin SR; Drug: Placebos

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dong Wu, M.D.; Phone Number: 8618612671010; Email: dongwu@pumc.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Dong Wu, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients ages 18-75 years admitted to Peking Union Medical College Hospital (PUMCH) with a diagnosis of AP based on at least 2 of the following criteria:
• Abdominal pain characteristic of AP
• Serum amylase and/or lipase ≥ 3 times the upper limit of normal
• Characteristic findings of AP on abdominal CT scan will be screened for study enrollment.

Exclusion Criteria:

• Onset time >48 hours
• Presence of renal dysfunction (serum creatinine > 1.5 *normal upper limit)
• Active peptic ulcer disease or GI bleeding
• Pregnancy or breast-feeding
• Use of daily antiplatelet or anticoagulant drug(s) within 2 week of presentation
• Hypersensitivity to NSAIDs
• New-onset, exacerbation or uncontrolled hypertension
• Presence of serious cardiovascular events, including severe heart failure, myocardial infarction (MI) and stroke
• Mental disability

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Indomethacin group; Indomethacin SR 50mg q12h from day1 to day 7 plus standard treatment for acute pancreatitis including adequate intravenous fluids, analgesics and early enteral nutrition support if possible.	Drug: Indomethacin SR; Indomethacin SR 50mg given q12h from admission day 1 to day 7; Other Names: YINDUOMEIXIN
Sham Comparator: Standard group; Similar shape and size suppositories without indomethacin (Placebos) given q12h from admission day 1 to day 7, plus standard treatment for acute pancreatitis including adequate intravenous fluids, analgesics and early enteral nutrition support if possible.	Drug: Placebos; Similar shape and size suppositories (Placebos) without indomethacin given q12h from admission day 1 to day 7; Other Names: sham

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurence rate of organ dysfunction	Accumulation of varied organ dysfunction, especially the cardiovascular, renal and respiratory systems	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurence rate of pancreatic necrosis	Accumulation of the key local complication of acute pancreatitis	1 month
Incidence rate of ICU admission	Evaluation of critical severe acute pancreatitis	1 month
Mortality	The number of deaths during a particular period of time	1 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization cost	Expense of acute pancreatitis	1 month

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: DONG WU, M.D., Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Gorsky VA, Agapov MA, Khoreva MV, Leonenko IV. The effect of lornoxicam on TLR2 and TLR4 messenger RNA expression and tumor necrosis factor-alpha, interleukin-6, and interleukin-8 secretion in patients with systemic complications of acute pancreatitis. Pancreas. 2015 Jul;44(5):824-30. doi: 10.1097/MPA.0000000000000344.

Helpful Links

• A small sample study of NSAIDs for treatment of acute pancreatitis

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Anticipated): July 1, 2020
• Study Completion (Anticipated): July 30, 2020

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (Actual): June 6, 2018

Study Record Updates

• Last Update Posted (Actual): December 14, 2018
• Last Update Submitted That Met QC Criteria: December 12, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Prognosis; Organ dysfunction; Acute pancreatitis; Indomethacin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Reproductive Control Agents; Gout Suppressants; Tocolytic Agents; Indomethacin
• Other Study ID Numbers: ZS-1413

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No