Clinical Trial Results:
Intraoperative clonidine for prevention of postoperative
agitation in children anaesthetised with sevoflurane
(PREVENT AGITATION): a randomised, placebo-controlled,
double-blind trial
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Summary
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EudraCT number |
2014-001466-10 |
Trial protocol |
DK |
Global end of trial date |
08 Dec 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Nov 2018
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First version publication date |
24 Nov 2018
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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 |
MY-clonidin-1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02361476 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
National Committee on Biomedical Research Ethics: H-2-2014-072, Danish Data Protection Agency: 30-1348 | ||
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Sponsors
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Sponsor organisation name |
Copenhagen University Hospital, Rigshospitalet, Juliane Marie Centre, Department of Anaesthesiology
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Sponsor organisation address |
Blegdamsvej 9, Copenhagen, Denmark, 2100
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Public contact |
Mogens Ydemann, Copenhagen University Hospital, Rigshospitalet, Juliane Marie Centre, Department of Anaesthesiology, mogens@ydemann.dk
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Scientific contact |
Mogens Ydemann, Copenhagen University Hospital, Rigshospitalet, Juliane Marie Centre, Department of Anaesthesiology, mogens@ydemann.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 |
08 Dec 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
08 Dec 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
08 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 |
We aimed to assess the effects of intravenous clonidine administered
intraoperatively on the incidence of postoperative agitation, pain, and adverse events.
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Protection of trial subjects |
All patients received the same protocol-based care.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jan 2015
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
1 Months | ||
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: 379
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Worldwide total number of subjects |
379
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EEA total number of subjects |
379
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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) |
89
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Children (2-11 years) |
290
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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 |
We recruited children between January and December, 2015, from: Rigshospitalet, Copenhagen University Hospital, Copenhagen; Vejle Hospital, Vejle, and Zealand University Hospital, Køge | |||||||||
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Pre-assignment
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Screening details |
Children aged 1–5 years, with an American Society of Anesthesiologists physical classification score of 1–2, who were scheduled for anaesthesia with sevoflurane and fentanyl. | |||||||||
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Period 1
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Period 1 title |
inclusion (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, Data analyst, Carer, Assessor | |||||||||
Blinding implementation details |
Vials were identical, we masked the trial to all participants,
investigators, other health-care providers, and statisticians. Additionally,
we extended the masking to the authors of the abstract for
this Article who initially drafted two versions
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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intervention | |||||||||
Arm description |
3 μg/kg of intravenous clonidine - around 20 min before the end of surgery. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
clonidine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
3 μg/kg of intravenous clonidine
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Arm title
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placebo | |||||||||
Arm description |
equal quantity of intravenous isotonic saline - around 20 min before completion of surgery | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
NaCl
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
equal quantity of intravenous isotonic saline
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Baseline characteristics reporting groups
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Reporting group title |
intervention
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Reporting group description |
3 μg/kg of intravenous clonidine - around 20 min before the end of surgery. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
placebo
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Reporting group description |
equal quantity of intravenous isotonic saline - around 20 min before completion of surgery | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
intervention
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Reporting group description |
3 μg/kg of intravenous clonidine - around 20 min before the end of surgery. | ||
Reporting group title |
placebo
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Reporting group description |
equal quantity of intravenous isotonic saline - around 20 min before completion of surgery | ||
Subject analysis set title |
Postoperative agitation
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Nine were excluded from the primary outcome analysis because of missing data points.
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End point title |
Postoperative agitation | ||||||||||||
End point description |
A Watcha score of more than 2 was considered as postoperative agitation.
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End point type |
Primary
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End point timeframe |
measured every 15 min in the POCU
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Statistical analysis title |
intention-to-treat | ||||||||||||
Statistical analysis description |
The proportion of patients with one or more incidence of agitation measured on the Watcha-Scale (scores 3 or 4).
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Comparison groups |
placebo v intervention
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Number of subjects included in analysis |
370
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
generalised linear models (GLM) | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
until discharge
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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 |
10
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Reporting groups
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Reporting group title |
intervention
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Reporting group description |
3 μg/kg of intravenous clonidine - around 20 min before the end of surgery. | ||||||||||||||||||||||||||||||
Reporting group title |
placebo
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Reporting group description |
equal quantity of intravenous isotonic saline - around 20 min before completion of surgery | ||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||
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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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09 Jul 2015 |
We increased the number of participants from 304 to 380. |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/30169192 |
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