Clinical Trial Results:
Does LOW Dose DEXmedetomidine After Cardiopulmonary Bypass Separation
Decrease the Incidence of DELirium: A Double-blind Randomized Placebocontrolled Study (LOWDEXDEL Study)
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Summary
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EudraCT number |
2017-002007-97 |
Trial protocol |
BE |
Global end of trial date |
30 Aug 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Feb 2021
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First version publication date |
17 Feb 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 |
2017/24JUL/374
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03388541 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Cliniques universitaires Saint-Luc
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Sponsor organisation address |
Avenue Hippocrate, 10, Brussels, Belgium, 1200
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Public contact |
Mona Momeni, Cliniques universitaires Saint-Luc, 0032 27647029, mona.momeni@uclouvain.be
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Scientific contact |
Mona Momeni, Cliniques universitaires Saint-Luc, 0032 27647029, mona.momeni@uclouvain.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 |
28 Oct 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Aug 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Aug 2019
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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 analyze whether the addition of a low dose DEXMEDETOMDINE to a sedation regimen based on propofol decreases the incidence of in-hospital delirium compared to propofol sedation with placebo in patients ≥ 60 years undergoing cardiac surgery
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Protection of trial subjects |
Any serious adverse events that would have occurred due to the study drug would have been reported to the IDMC. The patients are very closely monitored during the whole period when they receive Dexmedetomidine but also afterwards as they stay during several hours in the ICU. Otherwise, strict rules were followed to protect the subjects. In any case data regarding the patients were kept anonymous.
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Background therapy |
DEXMEDETOMIDINE was started at a dose of 0.4µg/kg/h (5ml/h) at the moment of the closure of the chest and continued during 10 hours. | ||
Evidence for comparator |
Placebo (NaCl 0.9%) was started at a continuous infusion of 5ml/h at the closure of the chest and was continued during 10 hours | ||
Actual start date of recruitment |
07 Dec 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 420
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Worldwide total number of subjects |
420
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EEA total number of subjects |
420
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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) |
0
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From 65 to 84 years |
408
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85 years and over |
12
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Recruitment
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Recruitment details |
Subjects were recruited from one single center (Cliniques Universitaires Saint Luc) | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Following written informed consent and before commencing treatment with Dexmedetomidine or Placebo, the patients were screened with Mini Mental State Examination test in order to evaluate the cognitive status of the patient. | ||||||||||||||||||||||||
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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 |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Assessor | ||||||||||||||||||||||||
Blinding implementation details |
Randomization and blinding performed by research Pharmacy of Cliniques Universitaires Saint Luc
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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DEXDOR | ||||||||||||||||||||||||
Arm description |
Patients receiving continuous IV infusion of dexmedetomidine | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
DEXMEDETOMIDINE
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Investigational medicinal product code |
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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 |
The drug was prepared at such that 5 ml/h corresponded to 0.4 µg/kg/h
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Arm title
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PLACEBO | ||||||||||||||||||||||||
Arm description |
Patients receiving continuous IV infusion of NaCl0.9% | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Sodium Chloride
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Investigational medicinal product code |
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Other name |
Isotonic saline solution, Normal saline solution, Physiological saline solution
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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 |
The drug was prepared without addition of any other substances and infused at a continuous IV infusion of 5 mL/H.
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Baseline characteristics reporting groups
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Reporting group title |
DEXDOR
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Reporting group description |
Patients receiving continuous IV infusion of dexmedetomidine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PLACEBO
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Reporting group description |
Patients receiving continuous IV infusion of NaCl0.9% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
DEXDOR
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Reporting group description |
Patients receiving continuous IV infusion of dexmedetomidine | ||
Reporting group title |
PLACEBO
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Reporting group description |
Patients receiving continuous IV infusion of NaCl0.9% | ||
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End point title |
Postoperative in-hospital delirium | |||||||||
End point description |
The primary outcome was the incidence of POD at any time during the patient's hospital stay. Delirium assessment in the ICU was performed once the Richmond Agitation-Sedation Scale was -3 and was based on the Confusion Assessment Method for intubated patients in the ICU (CAM-ICU). The nurses in the ICU evaluated POD every 8 hours with the French version of the CAM-ICU. Delirium assessment at the ward was performed twice a day (08.00 AM and 08.00 PM) with the CAM. Because POD is a fluctuating state, often presenting in the ward and at night, the chart review method was used to detect any episode of POD that was not diagnosed otherwise. The medical chart of the patients was checked for any notifications made by nurses or physicians suggesting for the occurrence of POD (e.g. aggressive, confusion, having been tied, use of haloperidol, hallucinations, inappropriate behaviour,..). Trained study staff then reviewed the medical chart.
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End point type |
Primary
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End point timeframe |
After surgical intervention
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Statistical analysis title |
Full study | |||||||||
Statistical analysis description |
The primary outcome was the incidence of POD at any time during the patient’s hospital stay. Delirium assessment in the ICU was performed once the Richmond Agitation Sedation Scale was ≥ 3 and was based on the Confusion Assessment Method for initiated patients in the ICU (CAM-ICU). The nurses in the ICU evaluated ÖD every 8 hours with French version of the CAM-ICU. Delerium Assessment at the ward was performed twice a day (8/00 AM and 08:00 PM). With the CAM. Because POD is fluctuating state, of
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Comparison groups |
DEXDOR v PLACEBO
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Number of subjects included in analysis |
408
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | |||||||||
P-value |
= 0.687 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
Mean difference (final values) | |||||||||
Point estimate |
0.89
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.52 | |||||||||
upper limit |
1.54 | |||||||||
| Notes [1] - This is a superiority trial with an alternative hypothesis being that adding a low dose DEX to propofol sedation would result in a different risk of POD compared to propofol with PL. |
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Adverse events information
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Timeframe for reporting adverse events |
After surgical intervention
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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 |
10.0
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Reporting groups
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Reporting group title |
DEXDOR
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Reporting group description |
Patients receiving continuous IV infusion of dexmedetomidine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PLACEBO
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Reporting group description |
Patients receiving continuous IV infusion of NaCl0.9% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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26 Nov 2018 |
An amendment was asked in order to increase the number of patients to include, as the incidence of POD in the Placebo group was lower than expected. We had initially planned to include a total number of 270 patients |
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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 | |||
