Clinical Trial Results:
Xenon as an adjuvant to propofol anaesthesia in patients undergoing off-pump coronary artery bypass graft surgery: a randomized controlled trial
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Summary
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EudraCT number |
2013-000485-11 |
Trial protocol |
BE |
Global end of trial date |
01 Dec 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Dec 2019
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First version publication date |
22 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 |
SR022013
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01948765 | ||
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 of the KU Leuven, 0032 16344620, christel.huygens@uzleuven.be
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Scientific contact |
Anesthesia Research, University Hospitals of the KU 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 |
01 Dec 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Mar 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Dec 2014
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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 aim of this study is to assess whether the administration of xenon as an adjuvant to propofol anesthesia is superior to anesthesia with propofol alone in patients undergoing off-pump coronary artery bypass surgery.
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Protection of trial subjects |
The interventional treatment was administered to patients under advanced hemodynamic monitoring in the setting of a fully equipped cardiac surgical operating room. This enables immediate detection and treatment of adverse events. Xenon inhalation was immediately stopped in case that the study patient shows a life-threatening deterioration. After leaving the operation room, all patients were closely monitored by the study team for the occurrence of eventual adverse or serious adverse events (S) AE’s during the whole postoperative period until hospital discharge. 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. Finally, suspected unexpected serious adverse reactions were reported by the principal investigator to the federal health authorities.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 May 2013
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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 |
6 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: 50
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Worldwide total number of subjects |
50
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EEA total number of subjects |
50
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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) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
18
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From 65 to 84 years |
32
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85 years and over |
0
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Recruitment
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Recruitment details |
After obtaining written informed consent, 50 patients scheduled for elective OPCAB surgery were enrolled in this prospective, single-centre, randomized, single-blinded controlled trial. Patients assessed for eligibility; (n = 86) Patients did not meet inclusion criteria; (n = 25) Patients decline to participate; (n= 11) | |||||||||
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Pre-assignment
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Screening details |
Eighty-six patients planned for elective coronary artery surgery in off-pump technique were screened from June 2013 to February 2014. A total of 50 patients were allocated randomly to receive either propofol-TCI alone (n = 25) or xenon 30%+propofol-TCI (n = 25). All patients received the allocated intervention, and no patient was lost to follow-up. | |||||||||
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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 |
Randomization was performed using a software-generated allocation sequence (QuickCalcs; GraphPad Software, La Jolla, CA). To avoid selection bias, we used a masked randomization process in which group assignments were hidden in closed, consecutively numbered envelopes that were only opened on arrival of the participant into the operation room. Two separate and independent investigators performed the study. Investigator I performed enrolment and the assessment of postoperative outcomes.
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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+propofol | |||||||||
Arm description |
30%Xenon with Propofol-TCI (n = 25). | |||||||||
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 |
30% xenon bases on EEG monitoring and clinical and hemodynamic signs.
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Investigational medicinal product name |
Propofol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Emulsion for injection/infusion in pre-filled syringe
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Routes of administration |
Intravenous drip use , Intravenous bolus use
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Dosage and administration details |
Propofol target-controlled infusion; doses were adjusted based on EEG-monitoring
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Arm title
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Propofol alone | |||||||||
Arm description |
propofol-TCI (n = 25) | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Propofol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Emulsion for injection/infusion
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Routes of administration |
Intravenous drip use , Intravenous bolus use
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Dosage and administration details |
propofol target-controlled infusion titrated based on EEG-monitoring and clinical signs of light anaesthesia (n = 25)
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Baseline characteristics reporting groups
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Reporting group title |
Xenon+propofol
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Reporting group description |
30%Xenon with Propofol-TCI (n = 25). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Propofol alone
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Reporting group description |
propofol-TCI (n = 25) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Xenon+propofol
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Reporting group description |
30%Xenon with Propofol-TCI (n = 25). | ||
Reporting group title |
Propofol alone
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Reporting group description |
propofol-TCI (n = 25) | ||
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End point title |
norepinephrine doses | ||||||||||||
End point description |
The primary outcome was intraoperative hemodynamic stability, which was quantified with the doses of norepinephrine required intraoperatively to accomplish the predefined hemodynamic targets (MAP > 70 mmHg).
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End point type |
Primary
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End point timeframe |
Start of anaesthesia induction to end surgery (Intraoperatively)
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Statistical analysis title |
Primary outcome | ||||||||||||
Statistical analysis description |
This trial was designed to demonstrate that the application of 30% xenon in addition to general anaesthesia with a TCI of propofol results in superior hemodynamics when compared to equipotent general anaesthesia with propofol alone.
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Comparison groups |
Xenon+propofol v Propofol alone
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Number of subjects included in analysis |
50
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Parameter type |
Median difference (final values) | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
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End point title |
Anesthesia depth (BIS) | ||||||||||||
End point description |
Depth of anaesthesia as assessed by the bispectral index (BIS) monitoring
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End point type |
Secondary
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End point timeframe |
Intraoperative
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Postoperatve delirium | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
In the first 5 postoperative days.
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Statistical analysis title |
Postoperative delirium | |||||||||
Comparison groups |
Propofol alone v Xenon+propofol
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Number of subjects included in analysis |
50
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
< 0.05 [1] | |||||||||
Method |
Fisher exact | |||||||||
Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
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upper limit |
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| Notes [1] - The incidence of postoperative delirium (pod) was similar between the groups; POD, n (%)= xenon-propofol 7 (28%) vs propofol alone 2 (8%); p = 0.138 |
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Adverse events information
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Timeframe for reporting adverse events |
From enrollment until patient's 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 |
23
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Reporting groups
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Reporting group title |
Xenon+propofol
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Reporting group description |
30%Xenon with Propofol-TCI (n = 25). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Propofol alone
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Reporting group description |
propofol-TCI (n = 25) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
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 | |||
