A Phase III Randomized, Double-blind, Dose-Controlled, Multicenter Study Evaluating the Safety and Efficacy of Dexmedetomidine in Intubated and Mechanically Ventilated Pediatric Intensive Care Unit Subjects
Overview
- Phase
- Phase 3
- Intervention
- Dexmedetomidine
- Conditions
- Sedation
- Sponsor
- Hospira, now a wholly owned subsidiary of Pfizer
- Enrollment
- 175
- Locations
- 35
- Primary Endpoint
- Percentage of Subjects That do Not Require Rescue Midazolam (MDZ) for Sedation Based on Achieving and Maintaining a Target University of Michigan Sedation Scale (UMSS) Score of 1 to 3 While Intubated.
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of dexmedetomidine (DEX) in intubated and mechanically ventilated pediatric intensive care unit (PICU) subjects. The key study objectives are:
- To characterize the loading and maintenance dosing of DEX by age group and overall medical condition of pediatric subjects
- To evaluate the safety and efficacy of loading and maintenance infusions for sedation in initially intubated and mechanically ventilated PICU subjects
- To explore the exposure-response relationship between dose of DEX and clinical measures of sedation and safety
Detailed Description
An estimated 175 subjects will be enrolled at approximately 40 investigative sites. Subjects will be divided into two treatment groups to receive either high dose or low dose Dexmedetomidine (DEX). The loading and maintenance doses in both groups will be stratified according to the presence or absence of cardiopulmonary bypass. The level of sedation will be assessed using the University of Michigan Sedation Scale (UMSS). Score 0 (awake/alert); Score 1 (sleepy/responds appropriately); Score 2 (somnolent/arouses to light stimuli); Score 3 (deep sleep/arouses to deeper); Score 4 (unarousable to stimuli). Based on these scores and clinical judgment, additional sedation with intravenous midazolam will be administered according to the label. The UMSS scores must be documented before the administration of every midazolam (MDZ) dose and within five minutes after each dose of MDZ. Fentanyl or morphine may be administered to treat pain. Subjects may be extubated after beginning of study drug but are not required to be as part of the study. The efficacy and safety parameters that will be monitored include sedation levels, heart rate, blood pressure and ventilation indicators. Once subjects have met site-specified respiratory criteria, they will undergo tracheal extubation. The dexmedetomidine infusion may be continued during and after extubation if further sedation is required post-extubation. The continuous infusion of dexmedetomidine must be administered for a minimum of 6 hours and a maximum of 24 hours. Sedation levels, heart rate, blood pressure, respiratory rate, ventilator settings, SpO2 and if available transcutaneous carbon dioxide (TcCO2) and/or arterial blood gases (ABG) will be monitored and recorded in the peri-extubation period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Initially intubated and mechanically ventilated pediatric subjects (≥1 month \[birth age corrected for prematurity\] to \<17 years of age) in an intensive care setting. The means by which the subject is intubated may include nasotracheal, endotracheal or via tracheotomy. The subject must be mechanically ventilated prior to and during the commencement of study drug.
- •Anticipated to require a minimum of 6 hours of continuous intravenous sedation.
- •American Society of Anesthesiologists (ASA) classification of 1, 2, 3 or
- •A UMSS score of 1, 2, 3 or 4 at the start of infusion of study drug.
- •A dose has been established for this subject's age based upon the diagnosis procedures.
- •Status post cardiopulmonary bypass (s/p CPB):
- •Low dose group: Loading dose: 0.2 mcg/kg Maintenance dose titration range (0.025-0.5 mcg/kg/hr)
- •High dose group: Loading dose: 0.5 mcg/kg Maintenance dose titration range (0.1-0.7 mcg/kg/hr)
- •All other diagnoses:
- •Low dose group: Loading dose: 0.3 mcg/kg Maintenance dose titration range (0.05- 0.5mcg/kg/hr)
Exclusion Criteria
- •Pediatric subjects with neurological conditions that prohibit an evaluation of sedation in the opinion of the investigator (e.g. increased intracranial pressure or extensive brain surgery).
- •The infusion pump minimal capacity cannot accommodate the lowest possible maintenance infusion rate of study drug based on subject's weight.
- •Subjects with second degree or third degree heart block unless subject has a pacemaker or pacing wires.
- •Hypotension that persist beyond a 15 min of re-assessments prior to starting study drug:
- •Age 1 month to ≤6 months old: systolic blood pressure (SBP) \<60 (millimeters of mercury) mmHg
- •Age \>6 months to \<2 yrs old: SBP \<70 mmHg
- •Age \>2 to \<12 yrs old: SBP \<80 mmHg
- •Age \>12 to \<17 yrs old: SBP \<90 mmHg
- •Pre-existing bradycardia that persists beyond a 15 min period of re-assessment prior to starting study drugs:
- •Age 1 month to \<2 months old: HR \<90 beats per min (bpm)
Arms & Interventions
Dexmedetomidine Low Dose
Intervention: Dexmedetomidine
Dexmedetomidine Low Dose
Intervention: Midazolam
Dexmedetomidine Low Dose
Intervention: Fentanyl
Dexmedetomidine Low Dose
Intervention: Morphine
Dexmedetomidine High dose
Intervention: Dexmedetomidine
Dexmedetomidine High dose
Intervention: Midazolam
Dexmedetomidine High dose
Intervention: Fentanyl
Dexmedetomidine High dose
Intervention: Morphine
Outcomes
Primary Outcomes
Percentage of Subjects That do Not Require Rescue Midazolam (MDZ) for Sedation Based on Achieving and Maintaining a Target University of Michigan Sedation Scale (UMSS) Score of 1 to 3 While Intubated.
Time Frame: 6 to 24 hours
Clinical Score Level of Sedation 0 Awake/Alert 1. Minimally Sedated: Tired/sleepy, appropriate response to verbal conversation and/or sounds. 2. Moderately Sedated: Somnolent/sleeping, easily aroused with light tactile stimulation. 3. Deeply sedated: Deep sleep, arousable only with significant physical stimulation. 4. Unarousable
Secondary Outcomes
- Total Amount of Rescue Medication Required for Sedation and Analgesia While Intubated(6 to 24 hours)
- Time to First Dose of Rescue Medication for Sedation and Analgesia(6 to 24 hours)
- Absolute Time on Study Drug That the Subject is in a UMSS Range of 1 to 3 While Intubated(6 to 24 hours)
- Absolute Time on Study Drug That the Subject is Out of the Target Sedation Range (UMSS <1 or >3) While Intubated(6 to 24 hours)
- Time to Successful Extubation(6 to 24 hours)