Clinical Trial Results:
Remifentanil tapering and post-adenotonsillectomy pain in children: a randomised, placebo controlled, double blind study
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Summary
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EudraCT number |
2019-001677-81 |
Trial protocol |
NO |
Global end of trial date |
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Nov 2023
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First version publication date |
03 Nov 2023
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Other versions |
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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 |
PTRS01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03994146 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Akershus Universitetssykehus
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Sponsor organisation address |
Sykehusveien 25, Lørenskog, Norway, 1478
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Public contact |
Principal Investigator, Akershus Universitetssykehus, william.james.morton@ahus.no
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Scientific contact |
Principal Investigator, Akershus Universitetssykehus, william.james.morton@ahus.no
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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 |
Interim
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Date of interim/final analysis |
18 Oct 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
No
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General information about the trial
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Main objective of the trial |
Tonsillectomy is the commonest operation of childhood and results in considerable pain.
Remifentanil is a potent, ultra short acting opiod with a long- established safety record in paediatric anaesthesia that is used to provide intraoperative analgesia.
There is evidence from adult studies that remifentanil paradoxically increases postoperative pain, although this may be ablated if propofol (rather than inhalational anaesthesia) is used or if the remifentanil is tapered rather than abruptly discontinued at the end of surgery.
The analgesic effect of gradual withdrawl of remifentanil at the end of surgery has not been studied in children and may have significant clinical implications.
The primary measure of efficacy will be the dose of fentanyl rescue analgesia in the perioperative period (1 mcg.kg-1 bolus for >20% increase in pulse, blood pressure or movement intraoperatively or a FLACC(Face, Legs, Arms, Cry, Consolablity) score of >5 in the recovery unit.
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Protection of trial subjects |
Independent clinician.
National data handling agreement.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Jan 2020
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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 |
Norway: 12
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Worldwide total number of subjects |
12
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EEA total number of subjects |
12
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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) |
12
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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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 |
Trial prematurely terminated due to poor recruitment. | |||||||||
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Pre-assignment
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Screening details |
American Society Anaesthesiology I-II children (1 to 10 years) Weight over 10.0 kg Presenting for tonsillectomy / tonsillotomy or adenotonsillectomy / tonsillotomy at Akershus Universitetssykehus, Lørenskog, or Lovisenberg Diakonale Hospital, Oslo, Norway | |||||||||
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Period 1
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Period 1 title |
Baseline (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 | |||||||||
Blinding implementation details |
Blinding conducted by sealed envelop.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Remifentanil tapering / Placebo abrupt cessation | |||||||||
Arm description |
Syringe one contains Remifentanil 2 mg in 40 ml NaCl 9 mg.ml-1 = 50 µg.ml-1 which will be infused at a rate of 0.9 µg.kg-1.min-1 and Syringe two contains 40 ml NaCl 9 mg.ml-1 at an identical infusion rate. According to randomisation syringe one will then be tapered towards the end of surgery and syringe two abruptly stopped. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Remifentanil
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravascular use
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Dosage and administration details |
Remifentanil 2 mg in 40 ml NaCl 9 mg.ml-1 = 50 µg.ml-1
infused at a rate of 0.9 µg.kg-1.min-1
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Arm title
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Placebo Tapering / Remifentanil Abrupt cessation. | |||||||||
Arm description |
Syringe one contains 40 ml NaCl 9 mg.ml-1 and Syringe two contains Remifentanil 2 mg in 40 ml NaCl 9 mg.ml-1 = 50 µg.ml-1 which will be infused at a rate of 0.9 µg.kg-1.min-1. According to randomization syringe one will be tapered towards the end of surgery and syringe two abruptly stopped | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Normal Saline 0.9%
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravascular use
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Dosage and administration details |
40 ml NaCl 9 mg.ml-1
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End points reporting groups
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Reporting group title |
Remifentanil tapering / Placebo abrupt cessation
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Reporting group description |
Syringe one contains Remifentanil 2 mg in 40 ml NaCl 9 mg.ml-1 = 50 µg.ml-1 which will be infused at a rate of 0.9 µg.kg-1.min-1 and Syringe two contains 40 ml NaCl 9 mg.ml-1 at an identical infusion rate. According to randomisation syringe one will then be tapered towards the end of surgery and syringe two abruptly stopped. | ||
Reporting group title |
Placebo Tapering / Remifentanil Abrupt cessation.
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Reporting group description |
Syringe one contains 40 ml NaCl 9 mg.ml-1 and Syringe two contains Remifentanil 2 mg in 40 ml NaCl 9 mg.ml-1 = 50 µg.ml-1 which will be infused at a rate of 0.9 µg.kg-1.min-1. According to randomization syringe one will be tapered towards the end of surgery and syringe two abruptly stopped | ||
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End point title |
Premature trial termination due to poor recruitment | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
06.01-2020 to 22.12.2021
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| Notes [1] - Premature trial termination due to poor recruitment |
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Statistical analysis title |
Premature trial termination | |||||||||
Statistical analysis description |
No statistical analysis due to premature trial termination due to poor recruitment.
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Comparison groups |
Remifentanil tapering / Placebo abrupt cessation v Placebo Tapering / Remifentanil Abrupt cessation.
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Number of subjects included in analysis |
12
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Analysis specification |
Pre-specified
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Analysis type |
superiority [2] | |||||||||
P-value |
< 0.05 [3] | |||||||||
Method |
Kruskal-wallis | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
10
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Confidence interval |
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level |
95% | |||||||||
sides |
1-sided
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lower limit |
5 | |||||||||
upper limit |
- | |||||||||
Variability estimate |
Standard deviation
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Dispersion value |
10
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| Notes [2] - No statistical analysis due to premature trial termination due to poor recruitment. [3] - No statistical analysis due to premature trial termination due to poor recruitment. |
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Adverse events information
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Timeframe for reporting adverse events |
06.01.2020 to 22.12.2021
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Assessment type |
Systematic | ||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||
Dictionary version |
2.1
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Reporting groups
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Reporting group title |
Remifenatil Tapering
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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? 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. | |||
| None reported | |||
