A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics

Study Description

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Brief Summary:

The purpose of this Phase I study is to determine the safety of a drug called dexmedetomidine (DEX) as part of a balanced general anesthetic and sedative strategy for neonates and infants undergoing corrective cardiac surgery that requires the use of cardiopulmonary bypass for congenital cardiac problems. This study will also design and validate a dosing schema for the use of DEX as described above.

Condition or disease	Intervention/treatment	Phase
Transposition of the Great Arteries; Tetralogy of Fallot; Ventricular Septal Defect	Drug: Dexmedetomidine	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	119 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics
Actual Study Start Date :	April 2, 2014
Actual Primary Completion Date :	October 16, 2017
Actual Study Completion Date :	October 17, 2017

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Neonate dosing cohort 1; Neonate dexmedetomidine dosing cohort 1	Drug: Dexmedetomidine; Other Name: Precedex, dexmedetomidine HCl
Experimental: Neonate dosing cohort 2; Neonate dexmedetomidine dosing cohort 2	Drug: Dexmedetomidine; Other Name: Precedex, dexmedetomidine HCl
Experimental: Neonate dosing cohort 3; Neonate dexmedetomidine dosing cohort 3	Drug: Dexmedetomidine; Other Name: Precedex, dexmedetomidine HCl
Experimental: Neonate dosing cohort 4; Neonate dexmedetomidine dosing cohort 4	Drug: Dexmedetomidine; Other Name: Precedex, dexmedetomidine HCl
Experimental: Neonate dosing cohort 5; Neonate dexmedetomidine dosing cohort 5	Drug: Dexmedetomidine; Other Name: Precedex, dexmedetomidine HCl
Experimental: Infant dosing cohort 1; Infant dexmedetomidine dosing cohort 1	Drug: Dexmedetomidine; Other Name: Precedex, dexmedetomidine HCl
Experimental: Infant dosing cohort 2; Infant dexmedetomidine dosing cohort 2	Drug: Dexmedetomidine; Other Name: Precedex, dexmedetomidine HCl
Experimental: Infant dosing cohort 3; Infant dexmedetomidine dosing cohort 3	Drug: Dexmedetomidine; Other Name: Precedex, dexmedetomidine HCl
Experimental: Infant dosing cohort 4; Infant dexmedetomidine dosing cohort 4	Drug: Dexmedetomidine; Other Name: Precedex, dexmedetomidine HCl
Experimental: Infant dosing cohort 5; Infant dexmedetomidine dosing cohort 5	Drug: Dexmedetomidine; Other Name: Precedex, dexmedetomidine HCl

Outcome Measures

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Primary Outcome Measures :

1. The occurrence of a safety event that is possibly, probably or definitely related to DEX administration [ Time Frame: Within 4 hours after DEX adminstration ]

   The occurrence of any of the following that is possibly, probably, or definitely related to DEX administration:

   • Bradycardia
   • Heart block
   • Junctional rhythm
   • Hypotension
   • Excessive sedation
   • Cardiac arrest or ECMO cannulation
   • Serious Adverse Event (SAE)

   Both the DEX dose, and DEX exposure will be assessed for associations with the primary outcome.

Secondary Outcome Measures :

1. Plasma concentration of DEX [ Time Frame: Intraoperatively and up to 36 hours post-operatively ]
   Plasma concentrations of dex obtained intraoperatively and up to 36 hours post-operatively will be used to create drug dosing models. These models will then be evaluated to determine how effective they are at achieving targeted plasma concentration levels.

Eligibility Criteria

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Ages Eligible for Study:	up to 180 Days (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Male or female, age 0 to 180 days at the time of surgery.
2. Diagnosis of: D-transposition of the great arteries (with or without ventricular septal defect), or tetralogy of Fallot, or ventricular septal defect (with or without associated atrial septal defect and/or patent ductus arteriosus)
3. Scheduled for complete corrective two-ventricle surgical repair with cardiopulmonary bypass.

Exclusion Criteria:

• 1. Less than 37 completed weeks' gestational age at birth for the Neonatal age group (0-21 days); less than 36 completed weeks' gestational age at birth for the Infant age group (22-180 days).

  2. Enrollment in the PHN Collaborative Learning Study, if tetralogy of Fallot 91-180 days of age only.

  3. Known or suspected hepatic dysfunction; AST and ALT >3X upper limit of normal at the time of screening within 72 hours of operation.

  4. Known or suspected renal dysfunction; serum creatinine > 0.8 mg/dL after 7 days of age, >1.2 mg/dL if <7 days of age, within 72 hours of operation.

  5. Preoperative administration of DEX or clonidine within 72 hours of operation.

  6. Major congenital anomaly(ies) outside the cardiovascular system that in the investigator's opinion would potentially affect safety or pharmacokinetics.

  7. Preoperative central nervous system injury resulting in clinical signs and symptoms: coma, seizures, hemiparesis.

  8. Planned period of deep hypothermic circulatory arrest. 9. History of second or third degree heart block. 10. Sinus or junctional bradycardia below 80 BPM sustained for greater than 15 minutes within 72 hours of operation. 11. Junctional rhythm sustained for greater than 15 minutes within 72 hours of operation.

  12. Hypotension defined as mean arterial blood pressure below 35 mm Hg for 0-21 day old neonatal patients, and below 40 mm Hg for 22-180 day old infant patients sustained for greater than 15 minutes within 72 hours of operation.

  13. History of cardiac arrest or ECMO cannulation.

Contacts and Locations

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Locations

United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02111
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Pennsylvania
Childrens Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030

Sponsors and Collaborators

New England Research Institutes

National Heart, Lung, and Blood Institute (NHLBI)

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	New England Research Institutes
ClinicalTrials.gov Identifier:	NCT01915277 History of Changes
Other Study ID Numbers:	PHN-DEX
First Posted:	August 2, 2013
Last Update Posted:	March 23, 2018
Last Verified:	March 2018

Keywords provided by New England Research Institutes:

Pediatric corrective cardiac surgery

Additional relevant MeSH terms:

Heart Septal Defects; Tetralogy of Fallot; Heart Septal Defects, Ventricular; Transposition of Great Vessels; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Dexmedetomidine; 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