Effects of Peripherally Acting µ-opioid Receptor Antagonists on Acute Pancreatitis

NCT04743570 | Completed Phase 2 DMC

• 3 other identifiers: PAMORA_AP, PAMORA-12020-002313-18N-20200060
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 4

Brief Summary

This study will investigate the effect of peripheral acting opioid antagonist (PAMORA) on the disease course of patients with acute inflammation of the pancreas (acute pancreatitis). The study will be conducted by treating hospitalized patients with acute pancreatitis with a PAMORA (methylnaltrexone).

Conditions

Acute Pancreatitis

Outcome Measures

Primary Outcomes (1)

• Pancreatitis activity scoring system

  Difference in Pancreatitis activity scoring system (PASS) score between the methylnaltrexone group and the placebo group. The PASS-score is a weighted score of presence of organ failure, number of criterias of Systemic Inflammatory Response Syndrome fulfilled, abdominal pain (0-10), morphine equivalent dose (mg) and tolerance to solid food. Minimum value is 0 and higher score is equal to higher disease activity. Documentation for the PASS can be found on the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519418/

  48 hours after randomization

Secondary Outcomes (16)

• Pancreatitis activity scoring system

  24 hours after randomization and every 24 hours untill end of study at day 5 (after 120 hours) and again at the day 14 follow-up visit

• Difference in assessments of circulating proinflammatory marker

  24 hours after randomization and every 24 hours untill end of study at day 5 (after 120 hours) and again at the day 14 follow-up visit

• Difference in assessments of circulating pro- and anti-inflammatory markers

  24 hours after randomization and every 24 hours untill end of study at day 5 (after 120 hours) and again at the day 14 follow-up visit

• Intestinal permeability

  From 48 to 72 hours after randomization

• Intestinal motility

  5 (+/- 1 day) after randomization

Study Arms (2)

Placebo treatment

PLACEBO COMPARATOR

Placebo consisting of Ringer's lactate in matched volume to active drug is added to 1000 mL Ringer's lactate solution and given as a continues infusion over 24 hours using an infusion pump.

Drug: Placebo treatment

Methylnaltrexone treatment

ACTIVE COMPARATOR

0.15 mg/kg methylnaltrexone will be dissolved in 1000 mL Ringer's lactate solution and given as a continues infusion over 24 hours using an infusion pump.

Drug: Methylnaltrexone treatment

Interventions

Placebo treatment DRUG

Active drug/placebo is given for the first 5 days of admission.

Placebo treatment

Methylnaltrexone treatment DRUG

Active drug/placebo is given for the first 5 days of admission.

Methylnaltrexone treatment

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent before any study specific procedures
• Able to read and understand Danish
• Male or female age between 18 and 80 years
• The researcher believes that the participant understands what the study entails, is capable of following instructions, can attend when needed, and is expected to complete the study
• The investigator will ensure that fertile female participants have a negative pregnancy test before treatment initiation and use contraception during the study period. The following methods of contraception, if properly used, are generally considered reliable: oral contraceptives, patch contraceptives, injection contraceptives, vaginal contraceptive ring, intrauterine device, surgical sterilization (bilateral tubal ligation), vasectomized partner, double barrier (condom and pessary), or sexual abstinence. Methods of contraception will be documented in the source documents
• At least two of the following criteria need to be fulfilled to establish a diagnosis of AP (according to the revised Atlanta criteria (16)): i) abdominal pain consistent with AP (acute onset of a persistent, severe, epigastric pain often radiating to the back); ii) serum amylase activity at least three times greater than the upper limit of normal; and iii) characteristic findings of AP on diagnostic imaging
• Predicted moderate or severe AP based on 2 or more systemic inflammatory response syndrome criteria upon admission

You may not qualify if:

• Definitive chronic pancreatitis according to the M-ANNHEIM criteria
• Known allergy towards study medication
• Known or suspected major stenosis or perforation of the intestines
• Known or suspected abdominal cancer (incl. intestine, pancreas and the biliary tree)
• Pre-existing renal insufficiency (defined as habitual estimated glomerular filtration rate below 45)
• Severe non-pancreaticobiliary infections or sepsis caused by non-pancreaticobiliary disease
• Child-Pugh class B or C liver cirrhosis
• Females that are currently lactating

Sponsors & Collaborators

• Asbjørn Mohr Drewes: lead
• Odense University Hospital: collaborator
• Hvidovre University Hospital: collaborator
• University Hospital Bispebjerg and Frederiksberg: collaborator

Study Sites (4)

Mech-Sense, Department of Medical Gastroenterology, Aalborg University Hospital

Aalborg, Jutland, 9000, Denmark

Location

Digestive Disease Center K, Bispebjerg University Hospital

Bispebjerg, Denmark

Location

Gastrounit, Hvidovre University Hospital

Hvidovre, Denmark

Location

Odense Pancreas Center

Svendborg, Denmark

Location

Related Publications (2)

• Knoph CS, Cook ME, Novovic S, Hansen MB, Mortensen MB, Nielsen LBJ, Hogsberg IM, Salomon C, Neergaard CEL, Aajwad AJ, Pandanaboyana S, Sorensen LS, Thorlacius-Ussing O, Frokjaer JB, Olesen SS, Drewes AM. No Effect of Methylnaltrexone on Acute Pancreatitis Severity: A Multicenter Randomized Controlled Trial. Am J Gastroenterol. 2024 Nov 1;119(11):2307-2316. doi: 10.14309/ajg.0000000000002904. Epub 2024 Jun 25.

  PMID: 38916223 DERIVED

• Knoph CS, Cook ME, Fjelsted CA, Novovic S, Mortensen MB, Nielsen LBJ, Hansen MB, Frokjaer JB, Olesen SS, Drewes AM. Effects of the peripherally acting mu-opioid receptor antagonist methylnaltrexone on acute pancreatitis severity: study protocol for a multicentre double-blind randomised placebo-controlled interventional trial, the PAMORA-AP trial. Trials. 2021 Dec 19;22(1):940. doi: 10.1186/s13063-021-05885-3.

  PMID: 34924020 DERIVED

MeSH Terms

Conditions

Pancreatitis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases

Study Officials

• Asbjørn M. Drewes, Professor

  Mech-Sense, Department of Medical Gastroenterology, Aalborg Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Chief Physician, MD, PhD, DMSc

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: February 8, 2021
• Study Start: May 14, 2021
• Primary Completion: April 9, 2023
• Study Completion: April 20, 2023
• Last Updated: April 21, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

DK (4)