Clinical Trial Results:
The use of xenon and dexmedetomidine for the prevention of postoperative emergence delirium after anaesthesia for pediatric cardiac catheterization: A randomized, controlled, observer-blinded pilot trial.
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Summary
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EudraCT number |
2018-002258-56 |
Trial protocol |
BE |
Global end of trial date |
10 Oct 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Dec 2021
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First version publication date |
13 Dec 2021
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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 |
SD-DXP
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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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 |
Department Anesthesiology-Research, University Hospitals Leuven, 32 16344620, christel.huygens@uzleuven.be
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Scientific contact |
Department Anesthesiology-Research, University Hospitals Leuven, 32 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 |
26 Feb 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 Oct 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Oct 2020
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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 |
The purpose of this pilot trial is to estimate the effect size for xenon-dexmedetomidine anaesthesia vs. sevoflurane anaesthesia with respect to the incidence of Emergency Delirium.
We hypothesize that in children undergoing cardiac catheterization, the use of dexmedetomidine as an adjunct to xenon-anesthesia reduces the incidence of ED when compared to the conventionally used anesthetic sevoflurane.
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Protection of trial subjects |
The interventional treatment was administered to patients with standard harm-dynamic monitoring in the setting of a fully equipped cardiac catheterisation room. This enabled immediate detection and treatment of adverse events. Xenon inhalation or dexmedetomidine infusion was to be immediately stopped in case that the pt showed a life-threatening deterioration. After leaving the operating room the patients were closely monitored by the study team for the occurrence of (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 facilitates reporting of (S)AE's to the principal investigator.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Dec 2018
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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 |
Belgium: 80
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Worldwide total number of subjects |
80
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EEA total number of subjects |
80
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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) |
56
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Children (2-11 years) |
24
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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 December 2018 to October 2020, 145 children scheduled for elective heart catheterization were screened. A total of 80 were included and randomized to receive GA either with xenon plus dexmedetomidine or sevoflurane. All patients received the allocated intervention. | |||||||||
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Pre-assignment
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Screening details |
We screened 145 consecutive children scheduled for heart catheterization under GA. Inclusion:children 1 mth-3 yrs.Exclusion criteria: lack of informed consent, cyanotic heart defect requiring FiO2> 50%, high-risk/complex interventional procedures,behavioural/cognitive deficit and contra-indication for studied drugs.We had screening failure of 65. | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
80 | |||||||||
Number of subjects completed |
80 | |||||||||
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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 |
Two investigator types conducted the trial. Investigator I accomplished all the postoperative visits and was, similar to the patient and his parents, blinded to treatment allocation. Investigator II performed randomization and general anesthesia and could not be blinded to the treatment due to the kind of intervention.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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dex/xenon | |||||||||
Arm description |
General anesthesia was maintained with xenon (50-65%)in oxygen and dexmedetomidine infusion (0.5-1.2µg/kg/uur) | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
xenon
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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 administration via inhalation via ET tube
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Investigational medicinal product name |
dexmedetomidine
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Investigational medicinal product code |
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Other name |
dexdor
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Pharmaceutical forms |
Injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
bolus dose was given 1µg/kg and continuous infusion was started at 0.5-11µg/kg/hr titrated following EEG
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Arm title
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sevoflurane | |||||||||
Arm description |
General anesthesia was maintained with sevoflurane (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 administration via inhalation via ET tube
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Baseline characteristics reporting groups
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Reporting group title |
dex/xenon
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Reporting group description |
General anesthesia was maintained with xenon (50-65%)in oxygen and dexmedetomidine infusion (0.5-1.2µg/kg/uur) | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
sevoflurane
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Reporting group description |
General anesthesia was maintained with sevoflurane (FiO2 0.25-0.4) | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
dex/xenon
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Reporting group description |
General anesthesia was maintained with xenon (50-65%)in oxygen and dexmedetomidine infusion (0.5-1.2µg/kg/uur) | ||
Reporting group title |
sevoflurane
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Reporting group description |
General anesthesia was maintained with sevoflurane (FiO2 0.25-0.4) | ||
Subject analysis set title |
xenon/dex
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Effect size estimation
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End point title |
• Incidence of ED as assessed by the Watcha-scale | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
60 minutes after extubation
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Statistical analysis title |
primary endpoint | ||||||||||||
Comparison groups |
sevoflurane v dex/xenon
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||
P-value |
< 0.1 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Confidence interval |
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| Notes [1] - effect size: The presented trial was designed as a pilot trial with the aim to estimate the effect size for xenon-dexmedetomidine anaesthesia vs. sevoflurane anaesthesia regarding the incidence of ED. |
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End point title |
ED as assessed by the PAEDScore | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
60 minutes after extubation
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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 |
From enrollment until the first postinterventional 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 |
dex/xenon
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Reporting group description |
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Reporting group title |
sevoflurane
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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14 Feb 2019 |
1. The loading dose of dexmedetomidine will be increased (1µg/kg instead of 0.5 µg/kg) and the continuous infusion will be titrated between 0.5 -1 µg/kg (instead of 0.3-0.8 with a maximum of 1µg/kg/h in case of insufficient depth of anesthesia ) in order to be equivalent to our clinical routine in children undergoing sedation for magnetic resonance imaging (2µg/kg dexmedetomidine as a bolus, followed by a 1 µg/kg bolus 20 minutes later) and in order to be equivalent to an ongoing international multicenter trial in which dexmedetomidine is also studied in a comparable patient population undergoing major surgery (for further information, see https://clinicaltrials.gov/ct2/show/NCT03089905). We have also seen in our first patients that the originally proposed doses of dexmedetomidine were too low to achieve an adequate depth of anaesthesia.
2. With respect to the titration of anaesthetic depth, we will in this version primarily rely on physiological signs indicative for a sufficient depth of anaesthesia (as the validity of the BIS-monitoring in little children remains controversial).
3. For the prophylaxis of postoperative nausea and vomiting, we will also administer ondansetron during the induction of anaesthesia. This is our institutional routine.
4. For rescue sedation, we will not administer a bolus of remifentanil, but a bolus of fentanyl.
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12 Nov 2019 |
extension of recruitment period |
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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 | |||
