Study Evaluating Safety and Efficacy of Dexmedetomidine (DEX) in Intubated and Mechanically Ventilated Pediatric Intensive Care Unit (PICU) Subjects - Full Text View

Purpose

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 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). 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 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 may be administered for a minimum of 6 hours and a maximum of one week. Sedation levels, heart rate, blood pressure, respiratory rate, transcutaneous CO2 or arterial blood gases (if available) and oxygen saturation will be monitored and recorded in the peri-extubation period.

Condition	Intervention	Phase
Sedation	Drug: Dexmedetomidine Drug: Midazolam Drug: Fentanyl Drug: Morphine	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

Drug Information available for: Morphine sulfate Fentanyl Fentanyl citrate Midazolam hydrochloride Dexmedetomidine Dexmedetomidine hydrochloride

U.S. FDA Resources

Further study details as provided by Hospira, Inc.:

Primary Outcome Measures:

Percentage of subjects that do not require rescue MDZ for sedation based on achieving and maintaining a target UMSS score of 1 3 while intubated. [ Time Frame: 6 to 24 hours ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Absolute time and percentage of time on study drug that the subject is in a UMSS range of 1 3 while intubated [ Time Frame: 6 to 24 hours ] [ Designated as safety issue: Yes ]
• Absolute time and percentage of time on study drug the subject is out of the target sedation range while intubated (UMSS score 0 or 4) [ Time Frame: 6 to 24 hours ] [ Designated as safety issue: Yes ]
Total amount of rescue medication required for sedation and analgesia [ Time Frame: 6 to 24 hours ] [ Designated as safety issue: Yes ]
Time to first dose of rescue medication for sedation and analgesia [ Time Frame: 6 to 24 hours ] [ Designated as safety issue: Yes ]
Time to extubation [ Time Frame: 6 to 24 hours ] [ Designated as safety issue: Yes ]

Enrollment:	175
Study Start Date:	December 2009
Study Completion Date:	December 2010
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Dexmedetomidine Low Dose	Drug: Dexmedetomidine Study drug titrated up or down to maintain target UMSS range. Drug: Midazolam Rescue medication for sedation according to UMSS scores Drug: Fentanyl Rescue medication for pain based on UMSS scores Drug: Morphine Rescue medication for pain based on UMSS scores.
Active Comparator: Dexmedetomidine High dose	Drug: Dexmedetomidine Study drug titrated up or down to maintain target UMSS range. Drug: Midazolam Rescue medication for sedation according to UMSS scores Drug: Fentanyl Rescue medication for pain based on UMSS scores Drug: Morphine Rescue medication for pain based on UMSS scores.

Eligibility

Ages Eligible for Study:	1 Month to 16 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.
Anticipated to require a minimum of 6 hours of continuous intravenous sedation.
ASA classification of 1, 2, 3, or 4.
Age range > 1 month to < 17 years old.
If female, subject is non-lactating and is either not of childbearing potential,or childbearing potential but is not pregnant at time of baseline.
Subject's parent(s) or legal guardian(s) has/have voluntarily signed and dated the informed consent document approved by the Institutional Review Board. Assent will be obtained where age-appropriate and according to state regulations.

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).
Age > 17 years.
Subjects with second degree or third degree heart block unless subject has a pacemaker or pacing wires.
Hypotension based on repeat assessments prior to starting study drug
Pre-existing bradycardia prior to starting study drugs
SGPT (ALT): 1 month - 12 months: > 165 U/L; > 12 months to 17 years: > 100 U/L.
Subjects who have a known allergy to dexmedetomidine, MDZ, morphine or fentanyl.
Requirement for medications other than DEX, midazolam, morphine or fentanyl for sedation and pain control.
Subjects with immobility form neuromuscular disease, paralysis from administration of neuromuscular blocking agents, spinal cord injury above T5, or subjects with muscle weakness form congenital or systemic medical illness etiologies.
Subjects who have received another investigational drug within the past 30 days.
Subjects who, in the opinion of the investigator, have any other condition where the risks of DEX would be expected to outweigh its benefits (e.g. cardiogenic shock on > 2 vasopressors).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00875550

Show 37 Study Locations

Sponsors and Collaborators

Hospira, Inc.

Investigators

Study Director:

Robert Bilkovski, MD

Medical Director, Hospira

More Information

No publications provided

Responsible Party:	Hospira, Inc.
ClinicalTrials.gov Identifier:	NCT00875550 History of Changes
Other Study ID Numbers:	DEX-08-05
Study First Received:	March 31, 2009
Last Updated:	January 4, 2012
Health Authority:	United States: Food and Drug Administration Canada: Health Canada

Keywords provided by Hospira, Inc.:

Intubated and mechanically ventilated PICU subjects

Additional relevant MeSH terms:

Midazolam
Fentanyl
Dexmedetomidine
Morphine
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Hypnotics and Sedatives
Anesthetics, Intravenous

Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Narcotics
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Analgesics, Opioid
Analgesics, Non-Narcotic
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists

ClinicalTrials.gov processed this record on May 19, 2013