Sedation Efficacy of Dexmedetomidine Versus Midazolam in Critically Ill Ventilated Children

Phase 3

Recruiting

• Conditions: Mechanically Ventilated, Critically Ill Children
• Interventions: Drug: Precedex; Drug: Midazolam

• Registration Number: NCT04082767
• Lead Sponsor: Douglas Fraser

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-08-28
• Study First Submitted QC: 2019-09-06
• Study First Posted: 2019-09-09
• Study Start: 2021-06-08
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-08
• Last Update Posted: 2023-12-11
• Primary Completion: 2024-09
• Study Completion: 2024-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Age is 1 month to 18 years inclusive
2. The patient is intubated and is expected to remain intubated for at least the next 48 hours
3. The patient has not been receiving mechanical ventilation for more than 72 hours
4. 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

1. Admission is a consequence of suspected or proven drug overdose
2. Patient is receiving dialysis
3. Known pregnancy or lactation
4. Neuromuscular blockade other than for intubation
5. General anesthesia in the 24 hours prior to study initiation
6. 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
7. Acute hepatitis or severe liver disease
8. Known history of sensitivity to midazolam and/or dexmedetomidine or their constituents
9. Systolic blood pressure (SBP) below 5th percentile for two consecutive measurements
10. Heart rate (HR) below 5th percentile for two consecutive measurements
11. 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
12. Previous enrollment into the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dexmedetomidine	Precedex	-
Midazolam	Midazolam	-

Primary Outcome Measures

Name	Time	Method
Target Sedation Range	Up to 14 days post-randomization	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

Name	Time	Method
Delirium	Up to 14 days post-randomization	Duration of delirium using raw and quantitative EEG
Pharmacokinetics - Area under the plasma concentration-time curve (AUC)	Up to 14 days post-randomization	Area under the plasma concentration-time curve (AUC)
Use of open label boluses for sedation - number	Up to 14 days post-randomization	Number of boluses (opioid and benzodiazepine) administered during the treatment period
Use of open label boluses for sedation - total dose	Up to 14 days post-randomization	Total dose of boluses (opioid and benzodiazepine) administered during the treatment period
Duration of mechanical ventilation	Up to 28 days post-randomization	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	Up to 90 days post-randomization	Length of stay will be calculated from the time of PCCU admission to the time of PCCU discharge.
Hospital Length of Stay	Up to 90 days post-randomization	Hospital Length of Stay will be calculated from the time of PCCU admission to the time of physical hospital discharge.
Adverse event (AE) occurrence	Randomization to 90 days post-randomization	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	Up to 14 days post-randomization	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)	Up to 14 days post-randomization	Maximum plasma concentration (Cmax)

Trial Locations

Locations (1)

Children's Hospital - London Health Sciences Centre; 🇨🇦 London, Ontario, Canada