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

Purpose

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	Intervention	Phase
Transposition of the Great Arteries Tetralogy of Fallot Ventricular Septal Defect	Drug: Dexmedetomidine	Phase 1


Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: Heart Surgery

Drug Information available for: Dexmedetomidine

Genetic and Rare Diseases Information Center resources: Tetralogy of Fallot Ventricular Septal Defects Transposition of the Great Arteries

U.S. FDA Resources

Further study details as provided by New England Research Institutes:

Primary Outcome Measures:

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:

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.


Estimated Enrollment:	106
Study Start Date:	March 2014
Estimated Study Completion Date:	July 2018
Estimated Primary Completion Date:	December 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility


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

Criteria

Inclusion Criteria:

Male or female, age 0 to 180 days at the time of surgery.
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)
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01915277

Contacts


Contact: Julie Miller, MPH, PMP	617-972-3197	jmiller@neriscience.com
Contact: Allison Crosby-Thompson, MS		acrosby-thompson@neriscience.com

Locations


United States, Massachusetts
Boston Children's Hospital	Recruiting
Boston, Massachusetts, United States, 02111
Contact phnmailbox@neriscience.com
United States, Michigan
University of Michigan	Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Nicole Wilder, MD 734-763-2435 nicowild@umich.edu
United States, Pennsylvania
Childrens Hospital of Philadelphia	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Susan Nicholson, MD 215-590-1874 nicholson@email.chop.edu
United States, Texas
Texas Children's Hospital	Recruiting
Houston, Texas, United States, 77030
Contact: Dean B Andropoulos, MD 832-826-5822 dbandrop@texaschildrens.org
Principal Investigator: Dean B Andropoulos, MD

Sponsors and Collaborators

New England Research Institutes

National Heart, Lung, and Blood Institute (NHLBI)

More Information


Responsible Party:	New England Research Institutes
ClinicalTrials.gov Identifier:	NCT01915277 History of Changes
Other Study ID Numbers:	PHN-DEX
Study First Received:	July 30, 2013
Last Updated:	April 4, 2017

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

ClinicalTrials.gov processed this record on September 21, 2017