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

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ClinicalTrials.gov Identifier: NCT00875550
Recruitment Status : Completed
First Posted : April 3, 2009
Results First Posted : October 30, 2014
Last Update Posted : August 14, 2015
Sponsor:
Information provided by (Responsible Party):
Hospira, now a wholly owned subsidiary of Pfizer

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

Condition or disease Intervention/treatment Phase
Sedation Drug: Dexmedetomidine Drug: Midazolam Drug: Fentanyl Drug: Morphine Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 175 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : January 2010
Actual Primary Completion Date : January 2011
Actual Study Completion Date : January 2011

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Absolute Time on Study Drug That the Subject is in a UMSS Range of 1 to 3 While Intubated [ Time Frame: 6 to 24 hours ]
  2. Absolute Time on Study Drug That the Subject is Out of the Target Sedation Range (UMSS <1 or >3) While Intubated [ Time Frame: 6 to 24 hours ]
  3. Total Amount of Rescue Medication Required for Sedation and Analgesia While Intubated [ Time Frame: 6 to 24 hours ]
  4. Time to First Dose of Rescue Medication for Sedation and Analgesia [ Time Frame: 6 to 24 hours ]
  5. Time to Successful Extubation [ Time Frame: 6 to 24 hours ]


Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Anticipated to require a minimum of 6 hours of continuous intravenous sedation.
  3. American Society of Anesthesiologists (ASA) classification of 1, 2, 3 or 4.
  4. A UMSS score of 1, 2, 3 or 4 at the start of infusion of study drug.
  5. 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)
    • High dose group: Loading dose: 0.6 mcg/kg Maintenance dose titration range (0.2 - 1.4 mcg/kg/hr)
  6. If female, subject is non-lactating and is either:

    1. Not of childbearing potential, defined as pre-menarche, or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
    2. Of childbearing potential but is not pregnant at time of baseline.
  7. 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:

  1. 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).
  2. The infusion pump minimal capacity cannot accommodate the lowest possible maintenance infusion rate of study drug based on subject's weight.
  3. Subjects with second degree or third degree heart block unless subject has a pacemaker or pacing wires.
  4. 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
  5. 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)
    • Age ≥2 months to <12 months old: HR <80 bpm
    • Age ≥12 months to <2 yrs old: HR <70 bpm
    • Age ≥ 2 to <12 yrs old: HR <60 bpm
    • Age ≥ 12 to <17 yrs old: HR <50 bpm
  6. Serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT): 1 month -12 months: >165 U/L; >12 months to <17 years: ≥100 U/L.

    Note: Subjects may be rescreened up to 6 hrs prior to study drug infusion (not including subjects undergoing cardiac surgery with CPB).

  7. Subjects who have a known allergy to dexmedetomidine, MDZ, morphine or fentanyl.
  8. Requirement for medications other than DEX, midazolam, morphine or fentanyl for sedation and pain control.
  9. 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. Note: subjects who received NMB agents intraoperatively must be, in the Investigator's opinion, free of residual neuromuscular blockade prior to dosing with study drug.
  10. Subjects who have received another investigational drug or device within the past 30 days.
  11. Subjects who have received DEX in a previous investigational trial within the previous 12 weeks.
  12. 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).
  13. Subjects who will require alpha-2 agonists/antagonists listed below within 48 hrs prior to baseline.

Alpha-2 Agonists: Xylazine*, Clonidine (Catapres, Dixarit), Guanfacine (Tenex), Guanabenz (Wytensin), Mivazerol, Guanadrel (Hylorel), Guanethidine (Ismelin) and Methyldopa (Aldomet). * Xylazine is a veterinary product, but has abuse potentIal in humans.

Alpha-2 Antagonists: Corynanthine, Phenoxybenzamine (Dibenzyline), Phentolamine (Regitine, Rogitine), Tolazoline (Priscoline), Yohimbine, Rauwolscine, Idazoxan, Reserpine (Serpasil) and Mirtazapine (Remeron, Remeron Soltab).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00875550


  Hide Study Locations
Locations
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United States, Arizona
Maricopa Medical Center
Phoenix, Arizona, United States, 85008
United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
United States, California
Loma Linda University Medical Center, Pediatric Dept., Div. of Critical Care - PICU
Loma Linda, California, United States, 92354
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Pediatric Critical Care
Los Angeles, California, United States, 90095
Dept. of Anesthesia, SUMC
Stanford, California, United States, 94305
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
Joe Dimaggio Children's Hospital/Memorial Regional Hospital, Pediatric Intensive Care Unit
Hollywood, Florida, United States, 33021
Critical Care
Jacksonville, Florida, United States, 32207
University of Miami - Miller School of Medicine
Miami, Florida, United States, 33136
Miami Children's Hospital
Miami, Florida, United States, 33155
Orlando, Florida, United States, 32806
Pensacola Research Consultants, Inc.
Pensacola, Florida, United States, 32504
United States, Illinois
University of Chicago Comer Children's Hospital
Chicago, Illinois, United States, 60637
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Advocate Lutheran General Children's Hospital
Park Ridge, Illinois, United States, 60068
United States, Kentucky
Kosair Charities Pediatric Clinical Research Unit, University of Louisville
Louisville, Kentucky, United States, 40202
United States, Maryland
The John Hopkins Medical Institutions, Anesthesia and Critical Care Medicine
Baltimore, Maryland, United States, 21287-8711
United States, Michigan
F3900 C.S. Mott Hospital SPC 5211 Dept. of Anaesthesiology
Ann Arbor, Michigan, United States, 48109-5211
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
United States, Minnesota
Gilette Children's Speciality Healthcare
Saint Paul, Minnesota, United States, 55101
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
United States, North Carolina
Duke University Medical Center, Department of Anesthesiology
Durham, North Carolina, United States, 27710
United States, Ohio
Akron Children's Hospital Medical Center
Akron, Ohio, United States, 44308
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
United States, Oregon
Northwest Pediatric Critical Care, P.C. Legacy Emanuel Children's Hospital
Portland, Oregon, United States, 97227
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, South Carolina
Medical University of South Carolina (MUSC)
Charleston, South Carolina, United States, 29425
United States, Texas
Children's Medical Center Dallas
Dallas, Texas, United States, 75235
United States, Virginia
University of Virginia, Division of Pediatric Critical Care
Charlottesville, Virginia, United States, 22908
Virginia Commonwealth University
Richmond, Virginia, United States, 23298-0530
United States, Wisconsin
Madison, Wisconsin, United States, 53792
Canada, British Columbia
BC Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Ontario
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H 8L1
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Pediatric Intensive Care Unit, CHU Sainte-Justine
Montreal, Quebec, Canada, H3T 1C5
Sponsors and Collaborators
Hospira, now a wholly owned subsidiary of Pfizer
Investigators
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Study Director: Robert Bilkovski, MD Medical Director, Hospira

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Responsible Party: Hospira, now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier: NCT00875550     History of Changes
Other Study ID Numbers: DEX-08-05
First Posted: April 3, 2009    Key Record Dates
Results First Posted: October 30, 2014
Last Update Posted: August 14, 2015
Last Verified: July 2015
Keywords provided by Hospira, now a wholly owned subsidiary of Pfizer:
Intubated and mechanically ventilated PICU subjects
Additional relevant MeSH terms:
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Fentanyl
Midazolam
Dexmedetomidine
Morphine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics, Opioid
Narcotics
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents