Clinical Trial Results:
Efficacy of profound versus moderate neuromuscular blockade in enhancing postoperative recovery after laparoscopic donor nephrectomy - a rondomised controlled trial
Summary
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EudraCT number |
2016-002924-99 |
Trial protocol |
NL |
Global end of trial date |
18 Dec 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Feb 2020
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First version publication date |
13 Feb 2020
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Other versions |
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Summary report(s) |
RELAX-1 article |
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 |
NL.58160.091.16
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02838134 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Radboudumc
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Sponsor organisation address |
Geert Grooteplein Zuid 10, Nijmegen, Netherlands, 6525 GA
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Public contact |
RELAX information, Radboudumc, +31 243615333, Michiel.Warle@radboudumc.nl
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Scientific contact |
RELAX information, Radboudumc, +31 243615333, Michiel.Warle@radboudumc.nl
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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 |
18 Dec 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Dec 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
18 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 |
To establish the relationship between the use of deep neuromuscular blockade (NMB) during laparoscopic donor nephrectomy (LDN) -with standard pressure pneumoperitoneum- and the early quality of recovery.
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Protection of trial subjects |
In accordance to section 10, subsection 4, of the WMO, the investigator will inform the subjects and the reviewing accredited METC if anything occurs, on the basis of which it appears that the disadvantages of participation may be significantly greater than was foreseen in the research proposal. The study will be suspended pending further review by the accredited METC, except insofar as suspension would jeopardise the subjects’ health. The investigator will take care that all subjects are kept informed.
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Background therapy |
induction with remifentanil, propofol and rocuronium (intubation dose 0.6 mg/kg). Anesthesia is aimed at a bispectral index score between 45-55. Tracheal intubation is performed 2 minutes after administration of 0.6 mg/kg rocuronium in both groups. In case of a BMI>30 kg/m2 the dose rocuronium will be adjusted taking into account ideal body weight. | ||
Evidence for comparator |
Rocuronium bromide is administered intravenously (i.v.) either as a bolus injection or as a continuous infusion. The standard intubating dose during routine anaesthesia is 0.6 mg rocuronium bromide per kg body weight, which results in adequate intubation conditions within 60 seconds in nearly all patients. | ||
Actual start date of recruitment |
01 Aug 2016
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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 |
Netherlands: 96
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Worldwide total number of subjects |
96
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EEA total number of subjects |
96
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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) |
75
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From 65 to 84 years |
21
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 127 living kidney donors were screened for enrolment, 18 patients refused consent, seven patients were excluded because of insufficient command of the Dutch language and one patient was excluded because of chronic use of psychotropic drugs. A total of 50 patients were allocated to profound NMB and 51 patients to moderate NMB. | |||||||||
Pre-assignment
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Screening details |
A total of 96 patients will be randomised, based on a computer-generated list, to either deep NMB (group A) or moderate NMB (group B). Stratification by centre will be used. All adult individuals (>18 years), who are scheduled for living kidney donation are eligible for this study. | |||||||||
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 |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer | |||||||||
Blinding implementation details |
Before the surgeons arrive at the operation room, all study medications are prepared by the anaesthesiologist or the anaesthesiologist’s assistant, after opening the envelope containing the allocation of treatment. Surgeons, scrub nurses, and research physician are blinded for group allocation. Covering of the neuromuscular monitoring equipment, nerve stimulator and computer behind sterile drapes ensures this. The attending anaesthetic staff in the operating room are not blinded as the anaesthe
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Deep neuromuscular block/group A | |||||||||
Arm description |
A bolus of 0.7 mg/kg rocuronium is administered just after tracheal intubation and then an infusion of rocuronium (0.3 to 0.4 mg/kg) is started when post-tetanic count (PTC) is more than 0 and titrated towards PTC 1-2. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Esmeron
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Investigational medicinal product code |
SUB10353MIG
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
A bolus of 0.7 mg/kg rocuronium is administered just after tracheal intubation and then an infusion of rocuronium (0.3 to 0.4 mg/kg) is started when post-tetanic count (PTC) is more than 0 and titrated towards PTC 1-2.
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Investigational medicinal product name |
Bridion
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Investigational medicinal product code |
SUB26695
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Other name |
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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 |
After skin closure, the NMB is reversed with sugammadex using 4 mg/kg
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Arm title
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Moderate neuromuscular block/group B | |||||||||
Arm description |
No additional rocuronium is administered after tracheal intubation. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Esmeron
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Investigational medicinal product code |
SUB10353MIG
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
A bolus of 0.7 mg/kg rocuronium is administered just after tracheal intubation. no additional rocuronium is administered after tracheal intubation and the neuromuscular function was allowed to recover spontaneously.
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Investigational medicinal product name |
Bridion
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Investigational medicinal product code |
SUB26695
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Other name |
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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 |
After skin closure, the NMB is reversed with sugammadex using 2 mg/kg
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
As-treated analysis: moderate block
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
In the as-treated analysis, we combined the patients with PTC 1to 3 and patients with TOF count 0 and PTC at least 4 in the profound NMB group. The five patients (10.4%) in which a TOF count 0 wasn’t achieved, were analysed as moderate NMB. The two patients in the profound NMB group with missing data on their level of NMB were excluded from the as-treated analysis.
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Subject analysis set title |
As treated analysis - deep block
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
In the as-treated analysis, we combined the patients with PTC 1to 3 and patients with TOF count 0 and PTC at least 4 in the profound NMB group. The five patients (10.4%) in which a TOF count 0 wasn’t achieved, were analysed as moderate NMB. The two patients in the profound NMB group with missing data on their level of NMB were excluded from the as-treated analysis.
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End points reporting groups
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Reporting group title |
Deep neuromuscular block/group A
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Reporting group description |
A bolus of 0.7 mg/kg rocuronium is administered just after tracheal intubation and then an infusion of rocuronium (0.3 to 0.4 mg/kg) is started when post-tetanic count (PTC) is more than 0 and titrated towards PTC 1-2. | ||
Reporting group title |
Moderate neuromuscular block/group B
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Reporting group description |
No additional rocuronium is administered after tracheal intubation. | ||
Subject analysis set title |
As-treated analysis: moderate block
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
In the as-treated analysis, we combined the patients with PTC 1to 3 and patients with TOF count 0 and PTC at least 4 in the profound NMB group. The five patients (10.4%) in which a TOF count 0 wasn’t achieved, were analysed as moderate NMB. The two patients in the profound NMB group with missing data on their level of NMB were excluded from the as-treated analysis.
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Subject analysis set title |
As treated analysis - deep block
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
In the as-treated analysis, we combined the patients with PTC 1to 3 and patients with TOF count 0 and PTC at least 4 in the profound NMB group. The five patients (10.4%) in which a TOF count 0 wasn’t achieved, were analysed as moderate NMB. The two patients in the profound NMB group with missing data on their level of NMB were excluded from the as-treated analysis.
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End point title |
Total Score of the Quality of Recovery-40 Questionnaire (QoR-40) | ||||||||||||||||||||
End point description |
The QoR-40 is a validated assessment tool for measuring a patient's self-assessed quality of recovery after surgery. It consists of 40 questions measuring 5 dimensions: patient support, comfort, emotions, physical independence and pain. Each item is rated on a scale of 1 to 5, giving a minimal score of 40 and a maximum score of 200. Higher values represent a better outcome
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End point type |
Primary
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End point timeframe |
24 hours after detubation
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Attachments |
QoR-40 questionnaire |
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Notes [1] - 1 patient missed one page of the QR-40 questionnaire on postoperative day 1 [2] - 1 patient did not complete the questionnaires on postoperative day 1 and 2 |
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Statistical analysis title |
QoR-40 | ||||||||||||||||||||
Comparison groups |
Deep neuromuscular block/group A v Moderate neuromuscular block/group B
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Number of subjects included in analysis |
94
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||
Confidence interval |
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End point title |
Postoperative pain | ||||||||||||||||||||
End point description |
Overall maximum painscore
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End point type |
Secondary
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End point timeframe |
Postoperative day 1
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Attachments |
Postoperative pain |
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Notes [3] - 1 patient did not complete the questionaires on postoperative day 1 and 2 |
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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 admission until 60 days after surgery
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
toetsingonline.nl | ||||||||||||||||||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Deep neuromuscular block/group A
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Reporting group description |
A bolus of 0.7 mg/kg rocuronium is administered just after tracheal intubation and then an infusion of rocuronium (0.3 to 0.4 mg/kg) is started when post-tetanic count (PTC) is more than 0 and titrated towards PTC 1-2. | ||||||||||||||||||||||||||||||||||||
Reporting group title |
Moderate neuromuscular block/group B
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Reporting group description |
No additional rocuronium is administered after tracheal intubation. | ||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||
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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 | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/30920983 |