SedationPhase 3NCT00875550
Study Evaluating Safety and Efficacy of Dexmedetomidine (DEX) in Intubated and Mechanically Ventilated Pediatric Intensive Care Unit (PICU) Subjects
A Phase 3 study testing Dexmedetomidine, Midazolam and Fentanyl in people with Sedation, run by Hospira, now a wholly owned subsidiary of Pfizer at 37 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 month to 16 years
- Conditions the study is for
- Sedation
- What is being tested?
- Dexmedetomidine, Midazolam and Fentanyl
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 175 participants
- Where
- 37 sitesin 2 countries
- Study dates
- Jan 2010to Jan 2011
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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 4.
- 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):
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- 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)
- If female, subject is non-lactating and is either:
- Not of childbearing potential, defined as pre-menarche, or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
- Of 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.
Who cannot join
- 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
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- 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)
- 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
- 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).
- 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. 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.
- Subjects who have received another investigational drug or device within the past 30 days.
- Subjects who have received DEX in a previous investigational trial within the previous 12 weeks.
- 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).
- 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).
Trial locations and contacts
37 sites in 2 countries.
37 sites in 2 countries
United States33 sites
Akron Children's Hospital Medical Center
Akron, Ohio, 44308
F3900 C.S. Mott Hospital SPC 5211 Dept. of Anaesthesiology
Ann Arbor, Michigan, 48109-5211
The John Hopkins Medical Institutions, Anesthesia and Critical Care Medicine
Baltimore, Maryland, 21287-8711
Medical University of South Carolina (MUSC)
Charleston, South Carolina, 29425
University of Virginia, Division of Pediatric Critical Care
Charlottesville, Virginia, 22908
University of Chicago Comer Children's Hospital
Chicago, Illinois, 60637
University Hospitals Case Medical Center
Cleveland, Ohio, 44106
MetroHealth Medical Center
Cleveland, Ohio, 44109
Children's Medical Center Dallas
Dallas, Texas, 75235
Children's Hospital of Michigan
Detroit, Michigan, 48201
Duke University Medical Center, Department of Anesthesiology
Durham, North Carolina, 27710
Joe Dimaggio Children's Hospital/Memorial Regional Hospital, Pediatric Intensive Care Unit
Hollywood, Florida, 33021
Critical Care
Jacksonville, Florida, 32207
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Loma Linda University Medical Center, Pediatric Dept., Div. of Critical Care - PICU
Loma Linda, California, 92354
Children's Hospital Los Angeles
Los Angeles, California, 90027
Pediatric Critical Care
Los Angeles, California, 90095
Kosair Charities Pediatric Clinical Research Unit, University of Louisville
Louisville, Kentucky, 40202
Study site
Madison, Wisconsin, 53792
Loyola University Medical Center
Maywood, Illinois, 60153
University of Miami - Miller School of Medicine
Miami, Florida, 33136
Miami Children's Hospital
Miami, Florida, 33155
Study site
Orlando, Florida, 32806
Advocate Lutheran General Children's Hospital
Park Ridge, Illinois, 60068
Pensacola Research Consultants, Inc.
Pensacola, Florida, 32504
Maricopa Medical Center
Phoenix, Arizona, 85008
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Northwest Pediatric Critical Care, P.C. Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
Virginia Commonwealth University
Richmond, Virginia, 23298-0530
Gilette Children's Speciality Healthcare
Saint Paul, Minnesota, 55101
Dept. of Anesthesia, SUMC
Stanford, California, 94305
Montefiore Medical Center
The Bronx, New York, 10467
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Canada4 sites
Pediatric Intensive Care Unit, CHU Sainte-Justine
Montreal, Quebec, H3T 1C5
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
BC Children's Hospital
Vancouver, British Columbia, V6H 3V4
About this study
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
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
Read the 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.
- Conditions
- Sedation
- Being tested
- Dexmedetomidine, Midazolam, Fentanyl, Morphine
- Keywords
- Intubated and mechanically ventilated PICU subjects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Study drug titrated up or down to maintain target UMSS range.
MidazolamDrug
Rescue medication for sedation according to UMSS scores
FentanylDrug
Rescue medication for pain based on UMSS scores
MorphineDrug
Rescue medication for pain based on UMSS scores.
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine Low Dose | Active comparator | Not described Receives: Drug: Dexmedetomidine; Drug: Midazolam; Drug: Fentanyl; Drug: Morphine |
| Dexmedetomidine High dose | Active comparator | Not described Receives: Drug: Dexmedetomidine; Drug: Midazolam; Drug: Fentanyl; Drug: Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Clinical Score Level of Sedation 0 Awake/Alert
- Minimally Sedated: Tired/sleepy, appropriate response to verbal conversation and/or sounds.
- Moderately Sedated: Somnolent/sleeping, easily aroused with light tactile stimulation.
- Deeply sedated: Deep sleep, arousable only with significant physical stimulation.
- Unarousable
Measured: 6 to 24 hours
Secondary outcomes (5)
Absolute Time on Study Drug That the Subject is in a UMSS Range of 1 to 3 While Intubated
Measured: 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
Measured: 6 to 24 hours
Total Amount of Rescue Medication Required for Sedation and Analgesia While Intubated
Measured: 6 to 24 hours
Time to First Dose of Rescue Medication for Sedation and Analgesia
Measured: 6 to 24 hours
Time to Successful Extubation
Measured: 6 to 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2009 (estimated)
- Study startJan 2010
- Primary completionJan 2011
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SedationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 175 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospira, now a wholly owned subsidiary of Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert Bilkovski, MD, Study director, Medical Director, Hospira
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00875550
- Sponsor's protocol ID
- DEX-08-05
- Status last verified
- Jul 2015
- First submitted
- 31 Mar 2009
- Last updated
- 14 Aug 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes