Back to resultsSedation Efficacy of Dexmedetomidine Versus Midazolam in Critically Ill Ventilated Children
Primary Purpose
Mechanically Ventilated, Critically Ill Children
Status
Recruiting
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Precedex
Midazolam
Sponsored by
About this trial
This is an interventional supportive care trial for Mechanically Ventilated, Critically Ill Children focused on measuring sedation, delirium, pediatric, critical care
Eligibility Criteria
Inclusion Criteria:
- Age is 1 month to 18 years inclusive
- The patient is intubated and is expected to remain intubated for at least the next 48 hours
- The patient has not been receiving mechanical ventilation for more than 72 hours
- The patient must already be receiving an opioid infusion per PCCU Guidelines for Sedation & Analgesia for Procedures Outside O.R. and need additional sedation.
Exclusion Criteria:
- Admission is a consequence of suspected or proven drug overdose
- Patient is receiving dialysis
- Known pregnancy or lactation
- Neuromuscular blockade other than for intubation
- General anesthesia in the 24 hours prior to study initiation
- An acquired Central Nervous System (CNS) condition (i.e. encephalitis, traumatic brain injury) resulting in ongoing dysfunction or an acquired condition resulting in ongoing dysfunction
- Acute hepatitis or severe liver disease
- Known history of sensitivity to midazolam and/or dexmedetomidine or their constituents
- Systolic blood pressure (SBP) below 5th percentile for two consecutive measurements
- Heart rate (HR) below 5th percentile for two consecutive measurements
- Death is deemed to be imminent or inevitable during the admission and either the intensivist or substitute decision maker is not committed to full active resuscitation
- Previous enrollment into the study
Sites / Locations
- Children's Hospital - London Health Sciences CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Dexmedetomidine
Midazolam
Arm Description
Outcomes
Primary Outcome Measures
Target Sedation Range
The percentage of time spent within target sedation range, defined as COMFORT Behaviour Scale score of 11-22, which will be assessed at minimum every 4 hours.
Secondary Outcome Measures
Delirium
Prevalence of delirium using the Cornell Assessment of Pediatric Delirium (CAPD) tool
Delirium
Duration of delirium using the Cornell Assessment of Pediatric Delirium (CAPD) tool
Delirium
Prevalence of delirium using raw and quantitative EEG
Delirium
Duration of delirium using raw and quantitative EEG
Duration of mechanical ventilation
Mechanical ventilation-free days through day 28 will be calculated as 28 minus the duration of mechanical ventilation. Participants who die, are still receiving mechanical ventilation, or are transferred from the PCCU still receiving mechanical ventilation by day 28 will be censored at 28 days and assigned zero mechanical ventilation-free days
PCCU Length of Stay
Length of stay will be calculated from the time of PCCU admission to the time of PCCU discharge.
Hospital Length of Stay
Hospital Length of Stay will be calculated from the time of PCCU admission to the time of physical hospital discharge.
Adverse event (AE) occurrence
Documentation of treatment related adverse events including blood pressure/heart rate changes requiring decreasing or discontinuation of study drug or intervention, delirium requiring medical treatment, any unplanned extubation or line removals, aspirations, ulcerations, etc.determined to result from inadequate sedation
Quantification of sleep stages and sleep quality assessment
Visual and automated scoring of sleep stages from EEG recordings Stage 1 sleep: scored when more than 15 seconds of the epoch is made up of theta activity (4to7 Hz) Stage 2 sleep: predominant theta activity (4 to 7 Hz) and occasional quick bursts of faster activity Stage 3/4 sleep: marked by high-amplitude slow waves Rapid eye movement (REM) sleep: characterized by low-amplitude, mixed-frequency theta waves, intermixed with some alpha waves (usually 1 to 2 Hz slower than wake).
Pharmacokinetics - Maximum plasma concentration (Cmax)
Maximum plasma concentration (Cmax)
Pharmacokinetics - Area under the plasma concentration-time curve (AUC)
Area under the plasma concentration-time curve (AUC)
Use of open label boluses for sedation - number
Number of boluses (opioid and benzodiazepine) administered during the treatment period
Use of open label boluses for sedation - total dose
Total dose of boluses (opioid and benzodiazepine) administered during the treatment period
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04082767
Brief Title
Sedation Efficacy of Dexmedetomidine Versus Midazolam in Critically Ill Ventilated Children
Official Title
Sedation Efficacy of Dexmedetomidine Versus Midazolam in Critically Ill Ventilated Children
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 8, 2021 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
May 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Douglas Fraser
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
There is a significant lack of adequately powered randomized clinical trial (RCT) data to determine the comparative safety and effectiveness of sedative treatments in pediatric patients. In many centres the standard of care for sedation in pediatric critical care unit (PCCU) patients includes the use of benzodiazepines despite the known negative effects of increased patient agitation and delirium, which can contribute to longer PCCU and hospital length of stay (LOS). The use of an alternative sedative, dexmedetomidine may reduce negative effects in this population. As such, the investigators plan to conduct a well designed comparative RCT to determine the most effective and safest sedative in this vulnerable population utilizing clinical assessments of sedation levels and delirium instance, electroencephalography (EEG) analysis and patient important outcomes.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mechanically Ventilated, Critically Ill Children
Keywords
sedation, delirium, pediatric, critical care
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dexmedetomidine
Arm Type
Active Comparator
Arm Title
Midazolam
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Precedex
Other Intervention Name(s)
dexmedetomidine
Intervention Description
Precedex, dexmedetomidine hydrochloride, IV, 4mcg/mL, infusion duration determined by the clinical care team
Intervention Type
Drug
Intervention Name(s)
Midazolam
Intervention Description
Midazolam, IV, 5mg/mL (for patients more than 10kg), 1mg/mL (for patients 2-10kg), infusion duration determined by the clinical care team
Primary Outcome Measure Information:
Title
Target Sedation Range
Description
The percentage of time spent within target sedation range, defined as COMFORT Behaviour Scale score of 11-22, which will be assessed at minimum every 4 hours.
Time Frame
Up to 14 days post-randomization
Secondary Outcome Measure Information:
Title
Delirium
Description
Prevalence of delirium using the Cornell Assessment of Pediatric Delirium (CAPD) tool
Time Frame
Up to 14 days post-randomization
Title
Delirium
Description
Duration of delirium using the Cornell Assessment of Pediatric Delirium (CAPD) tool
Time Frame
Up to 14 days post-randomization
Title
Delirium
Description
Prevalence of delirium using raw and quantitative EEG
Time Frame
Up to 14 days post-randomization
Title
Delirium
Description
Duration of delirium using raw and quantitative EEG
Time Frame
Up to 14 days post-randomization
Title
Duration of mechanical ventilation
Description
Mechanical ventilation-free days through day 28 will be calculated as 28 minus the duration of mechanical ventilation. Participants who die, are still receiving mechanical ventilation, or are transferred from the PCCU still receiving mechanical ventilation by day 28 will be censored at 28 days and assigned zero mechanical ventilation-free days
Time Frame
Up to 28 days post-randomization
Title
PCCU Length of Stay
Description
Length of stay will be calculated from the time of PCCU admission to the time of PCCU discharge.
Time Frame
Up to 90 days post-randomization
Title
Hospital Length of Stay
Description
Hospital Length of Stay will be calculated from the time of PCCU admission to the time of physical hospital discharge.
Time Frame
Up to 90 days post-randomization
Title
Adverse event (AE) occurrence
Description
Documentation of treatment related adverse events including blood pressure/heart rate changes requiring decreasing or discontinuation of study drug or intervention, delirium requiring medical treatment, any unplanned extubation or line removals, aspirations, ulcerations, etc.determined to result from inadequate sedation
Time Frame
Randomization to 90 days post-randomization
Title
Quantification of sleep stages and sleep quality assessment
Description
Visual and automated scoring of sleep stages from EEG recordings Stage 1 sleep: scored when more than 15 seconds of the epoch is made up of theta activity (4to7 Hz) Stage 2 sleep: predominant theta activity (4 to 7 Hz) and occasional quick bursts of faster activity Stage 3/4 sleep: marked by high-amplitude slow waves Rapid eye movement (REM) sleep: characterized by low-amplitude, mixed-frequency theta waves, intermixed with some alpha waves (usually 1 to 2 Hz slower than wake).
Time Frame
Up to 14 days post-randomization
Title
Pharmacokinetics - Maximum plasma concentration (Cmax)
Description
Maximum plasma concentration (Cmax)
Time Frame
Up to 14 days post-randomization
Title
Pharmacokinetics - Area under the plasma concentration-time curve (AUC)
Description
Area under the plasma concentration-time curve (AUC)
Time Frame
Up to 14 days post-randomization
Title
Use of open label boluses for sedation - number
Description
Number of boluses (opioid and benzodiazepine) administered during the treatment period
Time Frame
Up to 14 days post-randomization
Title
Use of open label boluses for sedation - total dose
Description
Total dose of boluses (opioid and benzodiazepine) administered during the treatment period
Time Frame
Up to 14 days post-randomization
Other Pre-specified Outcome Measures:
Title
Economic Analysis
Description
The investigators will perform an economic evaluation during this pilot trial. This will be cost estimate analysis based on approximate costs incurred daily in the PCCU. Costs will be determined at discharge from estimated cost per day of admission to the PCCU.
Time Frame
Up to 90 days post-randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age is 1 month to 18 years inclusive
The patient is intubated and is expected to remain intubated for at least the next 48 hours
The patient has not been receiving mechanical ventilation for more than 72 hours
The patient must already be receiving an opioid infusion per PCCU Guidelines for Sedation & Analgesia for Procedures Outside O.R. and need additional sedation.
Exclusion Criteria:
Admission is a consequence of suspected or proven drug overdose
Patient is receiving dialysis
Known pregnancy or lactation
Neuromuscular blockade other than for intubation
General anesthesia in the 24 hours prior to study initiation
An acquired Central Nervous System (CNS) condition (i.e. encephalitis, traumatic brain injury) resulting in ongoing dysfunction or an acquired condition resulting in ongoing dysfunction
Acute hepatitis or severe liver disease
Known history of sensitivity to midazolam and/or dexmedetomidine or their constituents
Systolic blood pressure (SBP) below 5th percentile for two consecutive measurements
Heart rate (HR) below 5th percentile for two consecutive measurements
Death is deemed to be imminent or inevitable during the admission and either the intensivist or substitute decision maker is not committed to full active resuscitation
Previous enrollment into the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maysaa Assaf, BSc
Phone
519-685-8500
Ext
77548
Email
maysaa.assaf@lhsc.on.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Douglas D Fraser, MD., PhD
Organizational Affiliation
Lawson Health Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital - London Health Sciences Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maysaa Assaf, BSc
Phone
519-685-8500
Ext
77548
Email
maysaa.assaf@lhsc.on.ca
First Name & Middle Initial & Last Name & Degree
Douglas D Fraser, MD/PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Sedation Efficacy of Dexmedetomidine Versus Midazolam in Critically Ill Ventilated Children
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