Clinical trial NCT04082767: 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
Overall status: RECRUITING
Phase: PHASE3
Conditions: Mechanically Ventilated, Critically Ill Children
Keywords: sedation, delirium, pediatric, critical care
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2019-09-09
Enrollment: 120
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Target Sedation Range
timeFrame: Up to 14 days post-randomization
Secondary outcomes:
measure: Delirium
timeFrame: Up to 14 days post-randomization
measure: Delirium
timeFrame: Up to 14 days post-randomization
measure: Delirium
timeFrame: Up to 14 days post-randomization
measure: Delirium
timeFrame: Up to 14 days post-randomization
measure: Duration of mechanical ventilation
timeFrame: Up to 28 days post-randomization
measure: PCCU Length of Stay
timeFrame: Up to 90 days post-randomization
measure: Hospital Length of Stay
timeFrame: Up to 90 days post-randomization
measure: Adverse event (AE) occurrence
timeFrame: Randomization to 90 days post-randomization
measure: Quantification of sleep stages and sleep quality assessment
timeFrame: Up to 14 days post-randomization
measure: Pharmacokinetics - Maximum plasma concentration (Cmax)
timeFrame: Up to 14 days post-randomization
measure: Pharmacokinetics - Area under the plasma concentration-time curve (AUC)
timeFrame: Up to 14 days post-randomization
measure: Use of open label boluses for sedation - number
timeFrame: Up to 14 days post-randomization
measure: Use of open label boluses for sedation - total dose
timeFrame: Up to 14 days post-randomization
Other outcomes:
measure: Economic Analysis
timeFrame: Up to 90 days post-randomization
Locations:
city: London
country: Canada
facility: Children's Hospital - London Health Sciences Centre
state: Ontario
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Douglas D Fraser, MD., PhD
role: PRINCIPAL_INVESTIGATOR
References: