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

• Status: Completed
• Trial end date: 2011-01-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hospira, Inc.; Hospira, now a wholly owned subsidiary of Pfizer
• Treatments: Dexmedetomidine; Fentanyl; Midazolam; Morphine

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).