Clinical Trial Results:
Paracetamol and setrons : drug interactions in the management of pain after tonsillectomy in children
|
Summary
|
|
EudraCT number |
2011-002213-12 |
Trial protocol |
FR |
Global end of trial date |
12 Jun 2012
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
27 May 2021
|
First version publication date |
27 May 2021
|
Other versions |
|
Summary report(s) |
Article |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
I10 005
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01432977 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
CHU de Limoges
|
||
Sponsor organisation address |
2 Avenue Martin Luther King, Limoges, France,
|
||
Public contact |
Principal Investigator, Pr Nathan-Denisot, nathan@unilim.fr
|
||
Scientific contact |
Principal Investigator, Pr Nathan-Denisot, 33 5 55 05 63 00, nathan@unilim.fr
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
11 Oct 2012
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
12 Jun 2012
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The main objectif of this study is to demonstrate that the association paracetamol / ondansetron is not as effective as the association paracetamol / droperidol in the treatment of pain in children following tonsillectomy.
|
||
Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable french regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research. The following additional measure(s) were in place for the protection of trial subjects:
All patients will receive injectable paracetamol at a dose of 15 mg / kg slowly from the start of surgery, then 15 mg / kg every 6 hours for the first 24 hours. The patient will therefore receive a total dose of 60 mg / kg per day in 4 administrations. In addition, Nifluril®, intra-rectally started in the operating room, at a dose of 400 mg / 10 kg in two doses per day will be administered to all patients for 24 hours.
During surgery, the anesthesiologist will administer an IV bolus of morphine of 75 µg / kg. Then in SSPI, a morphine titration at a dose of 25 μg / kg i.v. every ten minutes for a CHEOPS scale <8 at rest will be used.
If pain persists (CHEOPS scale> 8 at rest) after discharge from the SSPI in the department, codeine syrup (Codenfan®) will be administered at a dose of 0.5 mg / kg every 4 hours. If the pain persists (CHEOPS scale> 8 at rest), the dose of codeine administered will then be 0.75 mg / kg. Finally, in case of still persistent pain, a dose of codeine of 1 mg / kg will be administered. In case of persistent pain despite these treatments, a doctor will be contacted to decide on the patient's management.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 2011
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
France: 69
|
||
Worldwide total number of subjects |
69
|
||
EEA total number of subjects |
69
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
69
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
The study was carried out in the Hôpital Mère-Enfant of the Limoges University Hospital Center between October 2011 and June 2012. A total of 70 patients aged between 2 and 7 years scheduled for tonsillectomy ± adenoidectomy were included. | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
Patients aged between 2 and 7 years scheduled for tonsillectomy ± adenoidectomy were enrolled Exclusion criteria included a hospital stay of less than 24 hours, patients already on pain medication, and allergic patients with a contraindication to one of the study drugs. | |||||||||
|
Period 1
|
||||||||||
Period 1 title |
Overal trial (overall period)
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
|
|||||||||
Blinding used |
Single blind | |||||||||
Roles blinded |
Subject | |||||||||
Blinding implementation details |
The protocol will be carried out in simple blind. The two anti-emetics to be administered will not be known to the patient included, nor to the person collecting the CHEOPS and PONV scores, but may be known by the anesthesiologist or the nurse of the SSPI or the department.
This is because the first dose of ondansetron or droperidol will be administered during the surgery by the anesthesiologist or anesthesia nurse; but the person collecting the scores will not be able to know which substance.
|
|||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
Ondansetron | |||||||||
Arm description |
Patient will receive intravenously ondansetron at a dose of 0.1 mg / kg (dose1) along with betamethasone. After surgery, if the ANCOVA score is> 1, then the patient will receive a new ondansetron dose at a dose of 0.1 mg / Kg IV (dose 2). Thereafter, if the ANCOVA score is still> 1 droperidol dose at 0.05mg/kg will be administered (dose3). | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
ondansetron
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Solution for injection/infusion
|
|||||||||
Routes of administration |
Intravenous use
|
|||||||||
Dosage and administration details |
Patient will receive intravenously ondansetron at a dose of 0.1 mg / kg (dose1) along with betamethasone. After surgery, if the ANCOVA score is> 1, then the patient will receive a new ondansetron dose at a dose of 0.1 mg / Kg IV (dose 2).
|
|||||||||
|
Arm title
|
dorperidol | |||||||||
Arm description |
Patient will receive intravenously dorperidol at a dose of 0.05 mg / kg (dose1) along with betamethasone. After surgery, if the ANCOVA score is> 1, then the patient will receive again droperodol at a dose of 0.05 mg / kg (dose 2). Thereafter, if the ANCOVA score is still> 1 ondesetron at a dose of 0.1mg/kg will be administered (dose3). | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
dorperidol
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Solution for injection
|
|||||||||
Routes of administration |
Intravenous use
|
|||||||||
Dosage and administration details |
Patient will receive intravenously dorperidol at a dose of 0.05 mg / kg (dose1) along with betamethasone. After surgery, if the ANCOVA score is> 1, then the patient will receive again droperodol at a dose of 0.05 mg / kg (dose 2).
Thereafter, if the ANCOVA score is still> 1 ondesetron at a dose of 0.1mg/kg will be administered (dose3).
|
|||||||||
|
||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ondansetron
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patient will receive intravenously ondansetron at a dose of 0.1 mg / kg (dose1) along with betamethasone. After surgery, if the ANCOVA score is> 1, then the patient will receive a new ondansetron dose at a dose of 0.1 mg / Kg IV (dose 2). Thereafter, if the ANCOVA score is still> 1 droperidol dose at 0.05mg/kg will be administered (dose3). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
dorperidol
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patient will receive intravenously dorperidol at a dose of 0.05 mg / kg (dose1) along with betamethasone. After surgery, if the ANCOVA score is> 1, then the patient will receive again droperodol at a dose of 0.05 mg / kg (dose 2). Thereafter, if the ANCOVA score is still> 1 ondesetron at a dose of 0.1mg/kg will be administered (dose3). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Ondansetron
|
||
Reporting group description |
Patient will receive intravenously ondansetron at a dose of 0.1 mg / kg (dose1) along with betamethasone. After surgery, if the ANCOVA score is> 1, then the patient will receive a new ondansetron dose at a dose of 0.1 mg / Kg IV (dose 2). Thereafter, if the ANCOVA score is still> 1 droperidol dose at 0.05mg/kg will be administered (dose3). | ||
Reporting group title |
dorperidol
|
||
Reporting group description |
Patient will receive intravenously dorperidol at a dose of 0.05 mg / kg (dose1) along with betamethasone. After surgery, if the ANCOVA score is> 1, then the patient will receive again droperodol at a dose of 0.05 mg / kg (dose 2). Thereafter, if the ANCOVA score is still> 1 ondesetron at a dose of 0.1mg/kg will be administered (dose3). | ||
|
|||||||||||||
End point title |
postoperative pain score | ||||||||||||
End point description |
Assessed using CHEOPS (Children’s Hospital of Eastern Ontario Pain Scale)
It's a behavioural scale for evaluating post-operative pain in young children (McGrath et al., 1985). It has been validated
for children aged between 1 and 7 years [scores of 4 (normal) to 13 (maximum pain)] and it was used in this study.Pain scores were recorded by research nurses 30 min after admission and when leaving the recovery room, and then on the ward at 4 h after acetaminophen administration
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
4 h after the intraoperative co-administration of acetaminophen and ondansetron or droperidol,
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Wilcoxon | ||||||||||||
Comparison groups |
Ondansetron v dorperidol
|
||||||||||||
Number of subjects included in analysis |
69
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.2355 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||||
End point title |
Analysis of morphine and codeine consumption for 24 hours post intervention | ||||||||||||
End point description |
Comparison of the averages of morphine titrations in SSPI between group 1 and group 2.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
24 hours post intervention
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Wilcoxon | ||||||||||||
Comparison groups |
Ondansetron v dorperidol
|
||||||||||||
Number of subjects included in analysis |
69
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.0041 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
|
||||||||||
End point title |
Comparison of the cumulative incidences of nausea and vomiting 24 hours after surgery between group 1 and group 2 | |||||||||
End point description |
Comparison of the cumulative incidences of nausea and vomiting 24 hours after surgery between group 1 and group 2
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At 24 h after suirgery
|
|||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Until 24 h after the last patient visit
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ondansetron
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patient will receive intravenously ondansetron at a dose of 0.1 mg / kg (dose1) along with betamethasone. After surgery, if the ANCOVA score is> 1, then the patient will receive a new ondansetron dose at a dose of 0.1 mg / Kg IV (dose 2). Thereafter, if the ANCOVA score is still> 1 droperidol dose at 0.05mg/kg will be administered (dose3). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
dorperidol
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patient will receive intravenously dorperidol at a dose of 0.05 mg / kg (dose1) along with betamethasone. After surgery, if the ANCOVA score is> 1, then the patient will receive again droperodol at a dose of 0.05 mg / kg (dose 2). Thereafter, if the ANCOVA score is still> 1 ondesetron at a dose of 0.1mg/kg will be administered (dose3). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
