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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

Tracking Information
First Submitted Date  ICMJE March 31, 2009
First Posted Date  ICMJE April 3, 2009
Results First Submitted Date  ICMJE May 30, 2014
Results First Posted Date  ICMJE October 30, 2014
Last Update Posted Date August 14, 2015
Study Start Date  ICMJE January 2010
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 23, 2015)
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
Original Primary Outcome Measures  ICMJE
 (submitted: April 2, 2009)
The percent of subjects that do not require rescue midazolam for sedation based on achieving and maintaining a target UMSS score of 1-3 while intubated. [ Time Frame: 6 hours up to 1 week ]
Change History Complete list of historical versions of study NCT00875550 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2014)
  • 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 ]
  • 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 ]
  • Total Amount of Rescue Medication Required for Sedation and Analgesia While Intubated [ Time Frame: 6 to 24 hours ]
  • Time to First Dose of Rescue Medication for Sedation and Analgesia [ Time Frame: 6 to 24 hours ]
  • Time to Successful Extubation [ Time Frame: 6 to 24 hours ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating Safety and Efficacy of Dexmedetomidine (DEX) in Intubated and Mechanically Ventilated Pediatric Intensive Care Unit (PICU) Subjects
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Sedation
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • Active Comparator: Dexmedetomidine Low Dose
    Interventions:
    • Drug: Dexmedetomidine
    • Drug: Midazolam
    • Drug: Fentanyl
    • Drug: Morphine
  • Active Comparator: Dexmedetomidine High dose
    Interventions:
    • Drug: Dexmedetomidine
    • Drug: Midazolam
    • Drug: Fentanyl
    • Drug: Morphine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 2, 2009)
175
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2011
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Month to 16 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00875550
Other Study ID Numbers  ICMJE DEX-08-05
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hospira, now a wholly owned subsidiary of Pfizer
Study Sponsor  ICMJE Hospira, now a wholly owned subsidiary of Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Robert Bilkovski, MD Medical Director, Hospira
PRS Account Hospira, now a wholly owned subsidiary of Pfizer
Verification Date July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP