Clinical Trial Results:
The safety and feasibility of administering xenon to patients undergoing off-pump coronary artery bypass graft surgery: a pilot study
XOPCAB – Xenon in Off-Pump Coronary Artery Bypass Grafting
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Summary
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EudraCT number |
2012-002316-12 |
Trial protocol |
BE |
Global end of trial date |
14 Jan 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Dec 2019
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First version publication date |
20 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 |
SR052012
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01757106 | ||
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 016344620, christel.huygens@uzleuven.be
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Scientific contact |
Anesthesia Research, University Hospitals of the KU Leuven, 0032 016344620, christel.huygens@uzleuven.be
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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 |
Christel Huygens, Department of Anesthesiology, University Hospitals Leuven, 0032 16344720, christel.huygens@uzleuven.be
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Scientific contact |
Christel Huygens, Department of Anesthesiology, University Hospitals Leuven, 0032 16344720, 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 |
14 Jan 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Jul 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Jan 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 opioid-based xenon-anaesthesia is non-inferior to opioid-based sevoflurane anaesthesia in terms of haemodynamic stability (as reflected by vasopressor requirements). Secondary aims of the study included the assessment of various perioperative safety parameters.
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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 |
In noncardiac surgery, the noble gas xenon has been reported to produce only minimal haemodynamic side effects when compared with other anaesthetics, even in high-risk cardiovascular patients. These observations were confirmed by multicentre randomized controlled trials in which xenon was compared with isoflurane and was found to slightly decrease heart rate and to preserve or moderately increase arterial pressures. Such haemodynamic effects may result in an overall improvement of the balance between myocardial oxygen delivery and consumption. | ||
Evidence for comparator |
Wappler F, Rossaint R, Baumert J, et al. Multicenter randomized comparison of xenon and isoflurane on left ventricular function in patients undergoing elective surgery. Anesthesiology 2007; 106: 463–71. Rossaint R, Reyle-Hahn M, Schulte Am Esch J, et al. Multicenter randomized comparison of the efficacy and safety of xenon and isoflurane in patients undergoing elective surgery. Anesthesiology 2003; 98: 6–13. Stoppe C, Fahlenkamp AV, Rex S, et al. Feasibility and safety of xenon compared with sevoflurane anaesthesia in coronary surgical patients: a randomized controlled pilot study. Br J Anaesth 2013; 111: 406–16. | ||
Actual start date of recruitment |
03 Dec 2012
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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: 42
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Worldwide total number of subjects |
42
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EEA total number of subjects |
42
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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) |
7
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From 65 to 84 years |
33
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85 years and over |
2
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Recruitment
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Recruitment details |
After obtaining written informed consent, 42 patients scheduled for elective OPCAB surgery were enrolled in this prospective, single-centre, randomized, single-blinded, controlled pilot study. Patients recruitment started in December 2012 to July 2013, 79 patients scheduled for elective OPCAB surgery were screened. | |||||||||
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Pre-assignment
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Screening details |
Patients could be included if they were >18 years, scheduled for elective OPCAB surgery. Exclusion criteria were: lack of informed consent; chronic obstructive pulmonary disease(GOLD) stage >II; renal dysfunction, defined as serum creatinine >1.5mg/dl; acute coronary syndrome during the last 24h; LV EF≤30%; MMSE < 25, delirium at baseline, etc. | |||||||||
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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 |
A masked randomization procedure using sealed, opaque, sequentially numbered envelopes that were opened only upon arrival of the patient in the operating room (OR). Investigator I completed patient enrolment & postoperative follow-ups & was, like the patient, blinded to the study group. Investigator II performed randomization and general anaesthesia for OPCAB surgery and could not be blinded due to administration of the anaesthetic via a dedicated anaesthesia machine & the mandatory monitoring.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sevoflurane group | |||||||||
Arm description |
sevoflurane1.0 1.4% in oxygen and medicalair (FO2 =0.3–0.4). | |||||||||
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 endotracheal tube
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Arm title
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Xenon group | |||||||||
Arm description |
xenon 50–60% in oxygen [fraction of inspired oxygen (FO2 = 0.3–0.4)] . | |||||||||
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 application via inhalation via endotracheal tube
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Baseline characteristics reporting groups
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Reporting group title |
Sevoflurane group
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Reporting group description |
sevoflurane1.0 1.4% in oxygen and medicalair (FO2 =0.3–0.4). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Xenon group
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Reporting group description |
xenon 50–60% in oxygen [fraction of inspired oxygen (FO2 = 0.3–0.4)] . | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Sevoflurane group
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Reporting group description |
sevoflurane1.0 1.4% in oxygen and medicalair (FO2 =0.3–0.4). | ||
Reporting group title |
Xenon group
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Reporting group description |
xenon 50–60% in oxygen [fraction of inspired oxygen (FO2 = 0.3–0.4)] . | ||
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End point title |
Hemodynamic stability | ||||||||||||
End point description |
The primary outcome was the dose of noradrenaline that was required intraoperatively to achieve the predefined haemodynamic goals (Mean arterial pressure > 65 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 | ||||||||||||
Comparison groups |
Xenon group v Sevoflurane group
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Number of subjects included in analysis |
42
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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| Notes [1] - For the statistical analysis of the primary outcome, a 95% confidence interval (CI) was constructed for the ratio of the (geometric) mean comparing the intraoperative noradrenaline consumption of xenon with sevoflurane. For a single patient in the xenon group that did not require noradrenaline at all, the minimal observed consumption was assumed to allow the necessary log transformation. |
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Adverse events information
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Timeframe for reporting adverse events |
Patients randomization - hospital 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 |
Sevoflurane group
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Reporting group description |
sevoflurane1.0 1.4% in oxygen and medicalair (FO2 =0.3–0.4). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Xenon group
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Reporting group description |
xenon 50–60% in oxygen [fraction of inspired oxygen (FO2 = 0.3–0.4)] . | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? 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 | |||
