Clinical Trial Results:
Xenon as an adjuvant to sevoflurane anaesthesia in children undergoing interventional or diagnostic cardiac catheterization: a randomized controlled clinical trial
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Summary
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EudraCT number |
2014-002510-23 |
Trial protocol |
BE |
Global end of trial date |
12 Dec 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Dec 2019
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First version publication date |
18 Dec 2019
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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 |
SR062014
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University Hospitals Leuven
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Sponsor organisation address |
Herestraat 49, Leuven, Belgium, 3000
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Public contact |
Anesthesia research, University Hospitals Leuven, 0032 16344620, christel.huygens@uzleuven.be
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Scientific contact |
Anesthesia research, University Hospitals Leuven, 0032 16344620, christel.huygens@uzleuven.be
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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 Feb 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Dec 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Dec 2017
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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 |
As a primary study aim we hypothesized that the administration of 50% Xenon as an adjuvant to general anesthesia with sevoflurane is safe and feasible.
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Protection of trial subjects |
The interventional treatment was administered to patients with standard haemodynamic monitoring in the setting of a fully equipped cardiac catheterization room. This enabled immediate detection and treatment of adverse events. Xenon inhalation was to be immediately stopped in case that the study patient would show a life-threatening deterioration. Also after leaving the operation room, all patients were closely monitored by the study team for the occurrence of eventual (S)AE’s, first on the PACU, later on the normal ward. Moreover, the inclusion of each individual patient into the study was indicated in the electronic hospital information system and hence visible to all physicians and nurses involved in the care of this patient. This facilitated reporting of (S)AE’s to the principal investigator.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Sep 2014
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Scientific research | ||
Long term follow-up duration |
12 Months | ||
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 |
Belgium: 62
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Worldwide total number of subjects |
62
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EEA total number of subjects |
62
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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) |
62
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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 |
From November 2014 to November 2016, 40 children aged between 4 and 12 years old were included in this trial and random- ized to receive either xenon‐augmented sevoflurane or mono‐sevoflurane for the maintenance of the anesthesia. 22 age‐ and gender‐matched healthy and nonhospitalized children underwent the at comparable time intervals. | |||||||||
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Pre-assignment
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Screening details |
72 children were assessed for eligibility. A screening failure occurred in 32 children (7 refused, 14 met exclusion criteria, 11 had other reasons for exclusion). | |||||||||
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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 |
Randomised - controlled
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Blinding used |
Single blind | |||||||||
Roles blinded |
Subject | |||||||||
Blinding implementation details |
Subjects were allocated based on a closed envelope method [1:1 ratio, stratified by age (stratum I: age 4‐7 years; stratum II: 8‐12 years)]. 2 types of investigators conducted the trial. Inves- tigator I accomplished the enrollment on the day before the inter- vention and performed all postoperative visits. He was, as the patient and his parents, blinded to treatment allocation. Investigator II conducted the GA and was necessarily unblinded to the treatment due to the treatment conditions.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Xenon | |||||||||
Arm description |
General anesthesia with 50%‐65% xenon (LENOXeTM, AirLiquide Santé International, Paris, France) in oxygen (FiO2 = 0.25‐0.4) as an adjuvant to sevoflurane | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Xenon
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Investigational medicinal product code |
N01AX15
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Other name |
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Pharmaceutical forms |
Inhalation vapour
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Routes of administration |
Inhalation use
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Dosage and administration details |
50%‐65% xenon in oxygen (FiO2 = 0.25‐0.4) as an adjuvant to sevoflurane applied via inhalation by means of an endotracheal tube
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Investigational medicinal product name |
Sevoflurane
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation vapour
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Routes of administration |
Inhalation use
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Dosage and administration details |
EEG-titrated dosing, application via inhalation via endotracheal tube
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Arm title
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Sevoflurane | |||||||||
Arm description |
Sevoflurane (Sevorane, AbbVie, Wavre, Belgium) alone (FiO2 = 0.25‐0.4) | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Sevoflurane
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation vapour
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Routes of administration |
Inhalation use
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Dosage and administration details |
EEG-titrated dosing, application via inhalation via endotracheal tube
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: We included 62 children in total. 40 of them were randomized to receive general anesthesia. Twenty‐two additional healthy children matched for age and gender were included as control group for the neurocognitive assessments but received no treatment, neither with the IMP nor the active comparator. |
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Baseline characteristics reporting groups
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Reporting group title |
Xenon
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Reporting group description |
General anesthesia with 50%‐65% xenon (LENOXeTM, AirLiquide Santé International, Paris, France) in oxygen (FiO2 = 0.25‐0.4) as an adjuvant to sevoflurane | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sevoflurane
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Reporting group description |
Sevoflurane (Sevorane, AbbVie, Wavre, Belgium) alone (FiO2 = 0.25‐0.4) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Xenon
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Reporting group description |
General anesthesia with 50%‐65% xenon (LENOXeTM, AirLiquide Santé International, Paris, France) in oxygen (FiO2 = 0.25‐0.4) as an adjuvant to sevoflurane | ||
Reporting group title |
Sevoflurane
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Reporting group description |
Sevoflurane (Sevorane, AbbVie, Wavre, Belgium) alone (FiO2 = 0.25‐0.4) | ||
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End point title |
Hemodynamic instability | |||||||||
End point description |
Incidence of intraprocedural hemody- namic adverse events (not caused by obvious interventional manipulation), defined by a > 20% change from baseline for HR or MAP or by the need for fluid boluses, vasopressors, inotropes, or chronotropes.
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End point type |
Primary
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End point timeframe |
During administration of IMP
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Statistical analysis title |
Categorical endpoints | |||||||||
Statistical analysis description |
Statistical analysis was performed using SPSS 24 software (SPSS Statistics version 24 for Windows, IBM, Armonk, New York, United states) according to the intention‐to‐treat principle. Categorical data are summa- rized by observed frequencies and percentages and compared using Fisher's exact test.
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Comparison groups |
Xenon v Sevoflurane
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Number of subjects included in analysis |
40
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
= 1 | |||||||||
Method |
Fisher exact | |||||||||
Confidence interval |
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End point title |
Anesthetic depth | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
During administration of IMP
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Statistical analysis title |
Continuous variables | ||||||||||||
Statistical analysis description |
Continuous variables are reported using median and interquartile range (IQR) and were com- pared using the Mann‐Whitney U test.
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Comparison groups |
Sevoflurane v Xenon
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Number of subjects included in analysis |
40
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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| Notes [1] - Continuous variables are reported using median and interquartile range (IQR) and were compared using the Mann‐Whitney U test. |
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Adverse events information
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Timeframe for reporting adverse events |
From enrollment (the day before the intervention) until the first post-interventional day.
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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 |
23
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Reporting groups
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Reporting group title |
Xenon
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Reporting group description |
General anesthesia with 50%‐65% xenon (LENOXeTM, AirLiquide Santé International, Paris, France) in oxygen (FiO2 = 0.25‐0.4) as an adjuvant to sevoflurane | ||||||||||||||||||||||||||||||
Reporting group title |
Sevoflurane
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Reporting group description |
Sevoflurane (Sevorane, AbbVie, Wavre, Belgium) alone (FiO2 = 0.25‐0.4) | ||||||||||||||||||||||||||||||
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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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23 Nov 2015 |
20 healthy children will undergo the neuropsychological testing on three consecutive days in order to evaluate the effect of repeated testing. |
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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/30004615 http://www.ncbi.nlm.nih.gov/pubmed/31287192 |
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