Clinical Trial Results:
Intravenous Granisetron (Kytril) in the Prevention of Post-operative Nausea and Vomiting (PONV) in Pediatric Subjects Undergoing Tonsillectomy or Adenotonsillectomy
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Summary
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EudraCT number |
2016-003260-39 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
20 Dec 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Jul 2017
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First version publication date |
15 Jul 2017
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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 |
ML16633
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00231478 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Jun 2008
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Dec 2007
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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 |
To evaluate the effectiveness of two dose levels of intravenous (IV) granisetron (20 and 40 micrograms per kilogram [mcg/kg]) in preventing PONV, defined as total control (i.e., no nausea, no vomiting, no use of rescue medication) during the 2-hour interval following the time of extubation (end of surgery) in children aged 2 to 16 years.
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Protection of trial subjects |
The study was conducted in full conformance with the principles of the Declaration of Helsinki or with the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual. The study was fully adhere to the principles outlined in "guideline for Good Clinical Practice" of International Conference on Harmonisation (ICH) Tripartite Guideline (January 1997) or with local law if it afforded greater protection for the participants.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Apr 2007
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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 |
United States: 157
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Worldwide total number of subjects |
157
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EEA total number of subjects |
0
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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) |
145
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Adolescents (12-17 years) |
12
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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 |
- | ||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 171 pediatric participants undergoing elective tonsillectomy or adenotonsillectomy were randomized, 8 participants in the granisetron 20 mcg/kg dose group and and 6 participants in the 40 mcg/kg dose group did not receive study medication. Results are reported for 157 treated participants only. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (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, Carer | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Granisetron 20 mcg/kg | ||||||||||||||||||
Arm description |
Granisetron, 20 mcg/kg IV injection 15 minutes prior to end of surgery on Day 1. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Granisetron
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Investigational medicinal product code |
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Other name |
Kytril
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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 |
A single 30-second IV injection of granisetron solution.
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Arm title
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Granisetron 40 mcg/kg | ||||||||||||||||||
Arm description |
Granisetron, 40 mcg/kg IV injection 15 minutes prior to end of surgery on Day 1. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Granisetron
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Investigational medicinal product code |
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Other name |
Kytril
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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 |
A single 30-second IV injection of granisetron solution.
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Baseline characteristics reporting groups
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Reporting group title |
Granisetron 20 mcg/kg
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Reporting group description |
Granisetron, 20 mcg/kg IV injection 15 minutes prior to end of surgery on Day 1. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Granisetron 40 mcg/kg
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Reporting group description |
Granisetron, 40 mcg/kg IV injection 15 minutes prior to end of surgery on Day 1. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Granisetron 20 mcg/kg
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Reporting group description |
Granisetron, 20 mcg/kg IV injection 15 minutes prior to end of surgery on Day 1. | ||
Reporting group title |
Granisetron 40 mcg/kg
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Reporting group description |
Granisetron, 40 mcg/kg IV injection 15 minutes prior to end of surgery on Day 1. | ||
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End point title |
Percentage of Participants With Total Control of PONV Over the 2 hours Following Extubation [1] | ||||||||||||
End point description |
Percentage of participants with total control of PONV was defined as having no vomiting, no nausea, and no use of rescue medication after surgery.
Evaluable population included all randomized participants who received their single dose of study treatment and had a postdose assessment of nausea, vomiting, or use of rescue medication in the 24 hours following extubation.
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End point type |
Primary
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End point timeframe |
0-2 hours following extubation (end of surgery) on Day 1
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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: There was no formal hypothesis for this exploratory trial. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With Total Control of PONV Over the 24 hours Following Extubation | ||||||||||||
End point description |
Percentage of participants with total control was defined as no vomiting, no nausea, and no use of rescue medication after surgery.
Evaluable population.
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End point type |
Secondary
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End point timeframe |
0-24 hours following extubation (end of surgery) on Day 1
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With No Vomiting Over the 2 hours Following Extubation | ||||||||||||
End point description |
Percentage of participants with no vomiting is described as no emesis up to 2 hours after surgery.
Evaluable population.
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End point type |
Secondary
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End point timeframe |
0-2 hours following extubation (end of surgery) on Day 1
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With No Vomiting From the Time of Extubation Until Postanesthesia Care Unit (PACU) Discharge | ||||||||||||
End point description |
Any occurrence from the the time of extubation to PACU discharge were to be recorded at the PACU discharge assessment along with the time of PACU discharge.
Evaluable population.
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End point type |
Secondary
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End point timeframe |
0 hour following extubation (end of surgery) up to PACU discharge (up to 24 hours) on Day 1
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With No Vomiting Over the 24 hours Following Extubation | ||||||||||||
End point description |
Percentage of participants with no vomiting is described as no emesis up to 24 hours after surgery.
Evaluable population.
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End point type |
Secondary
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End point timeframe |
0-24 hours following extubation (end of surgery) on Day 1
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Time to First Vomiting Episode | ||||||||||||
End point description |
Time to first vomiting is described as the first event of emesis in hours. Participants not having a vomiting episode were censored at the total length of time (in hours) between the time of extubation and time of the 24 hour follow-up. Mean and standard error were estimated using Kaplan-Meier Survival Analysis.
Evaluable population.
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End point type |
Secondary
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End point timeframe |
0-24 hours following extubation (end of surgery) on Day 1
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With No Complaints of Nausea Over the 2 hours Following Extubation | ||||||||||||
End point description |
Percentage of participants with no complaints of nausea up to 2 hours after surgery were reported. Evaluable population.
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End point type |
Secondary
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End point timeframe |
0-2 hours following extubation (end of surgery) on Day 1
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With No Complaints of Nausea From the Time of Extubation Until PACU Discharge | ||||||||||||
End point description |
Any occurrence of nausea from the time of extubation until PACU discharge were to be recorded at the PACU discharge assessment along with the time of PACU discharge.
Evaluable population.
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End point type |
Secondary
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End point timeframe |
0 hour following extubation (end of surgery) up to PACU discharge (up to 24 hours) on Day 1
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With No Complaints of Nausea Over the 24 hours Following Extubation | ||||||||||||
End point description |
Percentage of participants with no complaints of nausea over 24 hours following the extubation were reported.
Evaluable population.
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End point type |
Secondary
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End point timeframe |
0-24 hours following extubation (end of surgery) on Day 1
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With No Rescue Medication Use | ||||||||||||
End point description |
Percentage of participants who did not require rescue medication from extubation until PACU discharge were reported.
Evaluable population.
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End point type |
Secondary
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End point timeframe |
0 hour following extubation (end of surgery) up to PACU discharge (up to 24 hours) on Day 1
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Time to First Use of Rescue Medication | ||||||||||||
End point description |
Any rescue medication used from the time of extubation up to 24 hours after extubation were to be recorded. If a rescue medication does not have any time indication, the time was set to equal the time of the earliest nausea episode or vomiting episode prior to discharge from the PACU. If a rescue medication does not have any time indication and no nausea or vomiting episodes are reported, the time of first rescue medication use was imputed as 1 minute following the time of extubation.
Participants not using rescue medication were censored at the total length of time (in hours) between the time of extubation and time of discharge from the PACU. Mean and standard error were estimated using Kaplan-Meier Survival Analysis.
Evaluable population.
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End point type |
Secondary
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End point timeframe |
0-24 hours following extubation (end of surgery) on Day 1
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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 |
Baseline up to 16 days
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.0
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Reporting groups
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Reporting group title |
Granisetron 20 mcg/kg
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Reporting group description |
Granisetron, 20 mcg/kg IV injection 15 minutes prior to end of surgery on Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Granisetron 40 mcg/kg
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Reporting group description |
Granisetron, 40 mcg/kg IV injection 15 minutes prior to end of surgery on Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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26 Jan 2007 |
Amendment 1: The primary and secondary objective and endpoint was clarified as the proportion of study participants with total control over the 2 and 24 hours following extubation, respectively. Secondary objectives and endpoints regarding the proportion of study participants who required granisetron 10 mcg/kg rescue due to prophylaxis failure and the response to granisetron rescue therapy were removed, secondary endpoints regarding the use of rescue medication no longer specified that rescue medication was granisetron 10 mcg/kg. Procedures regarding the use of rescue treatment were changed so as to specify that with the exception of 5-HT3 antagonists (prohibited). Additional secondary endpoints (proportions of study participants with vomiting and with/without complaints of nausea over different time periods) were provided to better support the secondary objective regarding the effectiveness of the two dose levels of granisetron. The exploratory objectives and endpoints regarding QT intervals and Chem-21 laboratory assessments were added. The maximum allowable granisetron dose of 3 milligrams (mg) was removed. |
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08 May 2007 |
Amendment 2: The intraoperative and post-operative dose of IV hydromorphone to be given as PACU analgesia was corrected (from 0.05 milligrams per kilogram [mg/kg] with a maximum dose of 1 mg to 0.005 mg/kg [no maximum dose provided]). |
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02 Jul 2007 |
Amendment 3: Clarified that intraoperative neuromuscular blockade was optional and that study participants who received it would also receive a neuromuscular blockade reversal agent. |
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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 | |||
