Clinical Trial Results:
The effects of opioid receptor antagonism on acute pancreatitis: An investigator initiated, randomized, placebo-controlled, double-blind clinical trial
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Summary
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EudraCT number |
2020-002313-18 |
Trial protocol |
DK |
Global end of trial date |
20 Apr 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Nov 2024
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First version publication date |
15 Nov 2024
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Other versions |
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Summary report(s) |
primary results publication |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
PAMORA-AP_2020
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04743570 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Aalborg University Hospital
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Sponsor organisation address |
Mølleparkvej 10, Aalborg, Denmark, 9000
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Public contact |
Asbjørn Mohr Drewes, Mech-Sense, Aalborg University Hospital, +45 97663520, amd@rn.dk
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Scientific contact |
Asbjørn Mohr Drewes, Mech-Sense, Aalborg University Hospital, +45 97663520, amd@rn.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
28 Feb 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Apr 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Apr 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
In patients admitted with acute pancreatitis, 5 days treatment with intravenous methylnaltrexone will significantly reduce the disease severity compared to placebo.
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Protection of trial subjects |
Most examinations (CT, blood samples, calculation of PASS-score) were adjusted to the standard of care so that subjects did not have to undergo additional examinations during acute illness. Furthermore, the study medication was administered continuously instead of as a bolus, to minimize side effects.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 May 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 105
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Worldwide total number of subjects |
105
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EEA total number of subjects |
105
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
71
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From 65 to 84 years |
34
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients admitted with AP were identified and contacted in the emergency department by study personnel upon or during admission. Information regarding current and previous medical conditions were passed on by the treatment-responsible physician from medical records to study personnel in order to identify eligible patients. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
We screened 748 patients and included 105 patients. The most common reason for screening failure was not meeting inclusion criteria (n = 584), most of these were due to less than 2 SIRS criteria (n = 414). Other reason for exclusion were: declining to participate (n = 25) or other reasons (e.g. early discharge or transfer to other hospital, n= 34) | |||||||||||||||||||||
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Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Assessor | |||||||||||||||||||||
Blinding implementation details |
Study medication was packaged and labeled into vials with methylnaltrexone and placebo having a similar appearance. Participants, study personnel, and treatment-responsible medical personnel were blinded to the allocation.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Methylnaltrexone | |||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
methylnaltrexone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Participants were randomized (1:1) to receive a daily amount of either 0.15 mg/kg methylnaltrexone or a corresponding volume of placebo (lactated Ringer). This dosage aligned with the approved subcutaneous use of methylnaltrexone for opioid-induced constipation14 and previous intravenous use for research purposes.18 The daily dose of methylnaltrexone or placebo was mixed in 1000 ml of lactated Ringer and delivered by continuous intravenous infusion over 24 hours, which was repeated daily for a maximum of five days. Daily doses were reduced by 50% for severe renal impairment (estimated glomerular filtration rate < 30 mL/min) during study participation, but otherwise, the daily doses were fixed based on admission weight.
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Arm title
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Lactated Ringer | |||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Lactated Ringer
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Participants were randomized (1:1) to receive a daily amount of either 0.15 mg/kg methylnaltrexone or a corresponding volume of placebo (lactated Ringer). This dosage aligned with the approved subcutaneous use of methylnaltrexone for opioid-induced constipation14 and previous intravenous use for research purposes.18 The daily dose of methylnaltrexone or placebo was mixed in 1000 ml of lactated Ringer and delivered by continuous intravenous infusion over 24 hours, which was repeated daily for a maximum of five days. Daily doses were reduced by 50% for severe renal impairment (estimated glomerular filtration rate < 30 mL/min) during study participation, but otherwise, the daily doses were fixed based on admission weight.
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End points reporting groups
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Reporting group title |
Methylnaltrexone
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Reporting group description |
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Reporting group title |
Lactated Ringer
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Reporting group description |
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End point title |
PASS-score | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
after 48 hours of treatment
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Statistical analysis title |
Mixed Model of Random Effects | |||||||||
Statistical analysis description |
For the primary outcome, differences between treatment groups were tested using a robust linear mixed model of repeated measures. We included terms for the assessment timepoint, treatment group, and interaction between the assessment timepoints and treatment group. From this model, we extracted point estimates for the mean PASS score, standard error of the mean (SEM), and the mean difference with a 95% confidence interval (CI) after 48 hours (primary endpoint).
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Comparison groups |
Methylnaltrexone v Lactated Ringer
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Number of subjects included in analysis |
91
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.87 | |||||||||
Method |
Mixed models analysis | |||||||||
Parameter type |
Mean difference (net) | |||||||||
Point estimate |
3.8
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
-40.1 | |||||||||
upper limit |
47.6 | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From time of screening until 45 hours after last administration of study treatment
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
SNOMED CT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Methylnaltrexone
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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18 Nov 2021 |
Until December 2021, we excluded patients with symptoms for more than 48 hours, but this criterion was omitted due to the lack of scientific rationale for 48 hours cut-off and stagnant enrollment |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
