Clinical Trial Results:
Effect of High-dose Target-controlled Naloxone Infusion on Pain and Hyperalgesia in Patients following Groin-Hernia-Repair.
A companion study to: Pharmacokinetics of High-dose Target-controlled Naloxone Infusion.
Summary
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EudraCT number |
2015-000793-36 |
Trial protocol |
DK |
Global end of trial date |
14 Dec 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
20 May 2021
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First version publication date |
20 May 2021
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Other versions |
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 |
HighNxGHR
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Multidisciplinary Pain Center 7612, Neuroscience Center
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Sponsor organisation address |
Blegdamsvej 9, Copenhagen, Denmark, 2100
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Public contact |
Mads U. Werner, Multidisciplinary Pain Center 7612, Neuroscience Center, Rigshospitalet, 0045 28257703, mads.u.werner@gmail.com
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Scientific contact |
Mads U. Werner, Multidisciplinary Pain Center 7612, Neuroscience Center, Rigshospitalet, 0045 28257703, mads.u.werner@gmail.com
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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 |
11 May 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Dec 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Dec 2015
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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 |
The principal aim of the study was to investigate the pharmacokinetic construct validity of a target-controlled-infusion (TCI) of naloxone.
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Protection of trial subjects |
During infusion of naloxone, participants will be monitored with ECG and measurements of pulse oximetry, blood pressure and respiratory rate. When naloxone is given, a physician and a nurse will be present if potential side effects should need any kind of treatment.
If requested by the participant, the rapid-onset, analgesic, rescue-opioid, alfentanil, will be administered, which, in less than one min completely will antagonize the effects of naloxone. Alfentanil is a well- known drug used in anaesthesia for immediate relief of acute pain. Alfentanil is initially given 7-15 microg/kg (1-2 ml/70 kg) and is administered in a titrated fashion until the desired analgesic effect is achieved. Common dose-dependent side effects are nausea, vomiting and sedation (> 10%). During the naloxone-infusion, the participant’s resting pain is monitored. The naloxone-infusion is immediately stopped if the participant experiences pain levels > 5 (NRS 0-10).
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Nov 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 8
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Worldwide total number of subjects |
8
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EEA total number of subjects |
8
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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) |
8
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The PK-participants will be recruited from our registry of volunteers who previously have participated in experimental pain studies at the Multidisciplinary Pain Center 7612, Rigshospitalet. | ||||||
Pre-assignment
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Screening details |
Evaluation by a physician. | ||||||
Pre-assignment period milestones
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Number of subjects started |
8 | ||||||
Number of subjects completed |
8 | ||||||
Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Arms
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Arm title
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Naloxone | ||||||
Arm description |
All subjects receiving naloxone infusion | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Naloxone
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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 |
Intravenous use
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Dosage and administration details |
Naloxone 4 mg/ml is delivered in glass ampoules of 100 ml (total content 400 mg). Naloxone is dissolved in a 0.9% NaCl solution: 1 liter of solution contains 9 grams of sodium chloride in sterile water (sodium-chloride 154 mmol/l; osmolarity 308 mmol/l).
A total dose of 3.25 mg/kg of naloxone will be administered in a step-wise approach for 75 minutes as follows: In the first minute (0-1 min) a bolus of 0.02 mg/kg will be given followed by an infusion of 0.23 mg/kg during 24 minutes (1-25 min). Afterwards (25-26 min) a bolus of 0.06 mg/kg will be administered followed by a 24-minute infusion of 0.69 mg/kg (min 26-50). Finally, a bolus of 0.18 mg/kg (50-51 min) will be given followed by a 24-minute infusion of 2.07 mg/kg (51-75 min).
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Final analysis
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All subjects in the study adhered to the same analysis set.
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End points reporting groups
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Reporting group title |
Naloxone
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Reporting group description |
All subjects receiving naloxone infusion | ||
Subject analysis set title |
Final analysis
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All subjects in the study adhered to the same analysis set.
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End point title |
Plasma concentration of naloxone [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Time-points during the TCI-infusion 17,20,23,41,44,47,67,70 and 75 min, and after 76,77,78, 79,80,82,86,94,110,142,206 and 334 min.
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analyses made in the current study was by population pharmacokinetics. This cannot be described by the terms provided here. No pairwise comparisons were made. |
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Attachments |
Concentration-time profiles for naloxone |
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No statistical analyses for this end point |
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End point title |
Plasma concentration of naloxone-3-glucuronide [2] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Time-points during the TCI-infusion 17,20,23,41,44,47,67,70 and 75 min, and after 76,77,78, 79,80,82,86,94,110,142,206 and 334 min.
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analyses made in the current study was by population pharmacokinetics. This cannot be described by the terms provided here. No pairwise comparisons were made. |
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Attachments |
Concentration-time profiles for naloxone |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From time 0 min when the infusion starts to time 340 min when the participant is discharged.
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Assessment type |
Systematic | ||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||
Dictionary version |
22
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Reporting groups
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Reporting group title |
Naloxone
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Reporting group description |
All subjects receiving naloxone infusion | ||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
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. | |||
The values for the endpoints given as mean (95%CI) do not provide valuable information, since the main objective of the current study is to measure concentrations of naloxone. We refer to the attached chart under the endpoints section. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/30915992 |