Rectal Indomethacin as Early Treatment for Acute Pancreatitis (INDOMAP Trial) (INDOMAP)

Rectal Indomethacin as Early Treatment for Acute Pancreatitis (INDOMAP Trial): Study Protocol for a Multi-center, Double-blinded, Placebo-controlled, Randomized Clinical Trial

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: Recruiting
• Conditions: Complication; Acute Pancreatitis; Mortality Rate; Organ Failure, Multiple
• Intervention / Treatment: Drug: Indomethacin SR; Drug: Placebos

• Study Type: Interventional
• Enrollment (Estimated): 1504
• Phase: Phase 4

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.
    • Beijing, Beijing, China, 100191
      • Recruiting
      • Peking University Sixth Hospital
      • Contact: Zuoyan Wu, MD
    • Beijing, Beijing, China, 102401
      • Recruiting
      • Liangxiang Hospital
      • Contact: Yanfeng Wang, M.D.
  • Guizhou
    • Guiyang, Guizhou, China, 550005
      • Recruiting
      • Guiyang Second People's Hospital
      • Contact: Shanshan Yu, M.D.
  • Hebei
    • Baoding, Hebei, China, 071000
      • Recruiting
      • Baoding Seventh Hospital
      • Contact: Zhitao Lu, M.D.
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Recruiting
      • Fourth Affiliated Hospital of Harbin Medical University
      • Contact: Ruifeng Wang, MD
  • Henan
    • Dengzhou, Henan, China, 411381
      • Recruiting
      • Dengzhou People's Hospital
      • Contact: Na Wu, M.D.
    • Nanyang, Henan, China, 473012
      • Recruiting
      • Second People Hospital of Nanyang
      • Contact: Xiao Fan, M.D.
  • Jiangsu
    • Huaian, Jiangsu, China, 223300
      • Recruiting
      • The Second People's Hospital of Huai'an
      • Contact: Yan Shi, MD
    • Nantong, Jiangsu, China, 226001
      • Recruiting
      • Nantong First People's Hospital
      • Contact: Baofeng Zhu, MD
    • Suqian, Jiangsu, China, 223800
      • Recruiting
      • Suqian People's Hospital
      • Contact: Ming Sun, MD
    • Wuxi, Jiangsu, China, 214043
      • Recruiting
      • Wuxi Third People's Hospital
      • Contact: Wei Huang, MD
  • Qinghai
    • Xining, Qinghai, China, 810001
      • Recruiting
      • Qinghai University Affiliated Hospital
      • Contact: Mei Liu, M.D.
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Longquan Hospital Sichuan University
      • Contact: Shicheng Zheng, MD
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830054
      • Recruiting
      • The First Affiliated Hospital of Xinjiang Medical University
      • Contact: Jianzhong Yang, MD
  • Zhejiang
    • Jinhua, Zhejiang, China, 321000
      • Recruiting
      • Jinhua Municipal Central Hospital
      • Contact: Daoyuan Jing, MD
    • Lishui, Zhejiang, China, 323000
      • Recruiting
      • Lishui Municipal Central Hospital
      • Contact: Hong Liu, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All patients ages 18-80 years 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 >24 hours
• Presence of renal dysfunction (serum creatinine > 1.5 *normal upper limit)
• Severe liver dysfunction
• Active peptic ulcer disease or GI bleeding
• Pregnancy or breast-feeding
• 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
• Malignancy-associated acute pancreatitis
• Post-ERCP pancreatitis
• Informed consent not signed

Study Plan

How is the study designed?

Design Details

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

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 caused by acute pancreatitis	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: Study Chair: Dong Wu, M.D., Peking Union Medical College Hospital; Principal Investigator: Zhitao Lu, M.D., Baoding Seventh Hospital; Principal Investigator: Yanfeng Wang, M.D., Liangxiang Hospital; Principal Investigator: Shanshan Yu, M.D., Guiyang Second People's Hospital; Principal Investigator: Na Wu, M.D., Dengzhou People's Hospital; Principal Investigator: Mei Liu, M.D., Affiliated Hospital of Qinghai University; Principal Investigator: Xiao Fan, M.D., Second People Hospital of Nanyang; Principal Investigator: Zuoyan Wu, MD, Peking University Sixth Hospital; Principal Investigator: Ruifeng Wang, MD, Harbin Medical University; Principal Investigator: Baofeng Zhu, MD, Nantong First People's Hospital; Principal Investigator: Yan Shi, MD, The Second People's Hospital of Huai'an; Principal Investigator: Ming Sun, MD, Suqian People's Hospital; Principal Investigator: Wei Huang, MD, Wuxi Third People's Hospital; Principal Investigator: Shicheng Zheng, MD, West China Longquan Hospital Sichuan University; Principal Investigator: Jianzhong Yang, MD, First Affiliated Hospital of Xinjiang Medical University; Principal Investigator: Daoyuan Jing, MD, Jinhua Municipal Central Hospital; Principal Investigator: Hong Liu, MD, Lishui Municipal Central 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): December 1, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028

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): June 15, 2025
• Last Update Submitted That Met QC Criteria: June 11, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Prognosis; Organ dysfunction; Acute pancreatitis; Indomethacin
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Pancreatic Diseases; Shock; Pancreatitis; Multiple Organ Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Gout Suppressants; Antirheumatic Agents; Reproductive Control Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Tocolytic Agents; Indomethacin
• Other Study ID Numbers: I-23PJ1671

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