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Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
This study is not yet open for participant recruitment.
Verified by Vanderbilt University, October 2008
Sponsored by: Vanderbilt University
Information provided by: Vanderbilt University
ClinicalTrials.gov Identifier: NCT00770705
  Purpose

Phenoxybenzamine, an irreversible alpha-adrenergic blocker, may prove beneficial to infants and children with congenital heart disease undergoing open cardiac repair, due to a theoretic benefits of a uniform and smooth reduction in systemic vascular resistance in the perioperative period. Vasodilation allows for low pressure, high flow systemic perfusion while on cardiopulmonary bypass. Support for the use of phenoxybenzamine in humans has been documented in several studies involving the perioperative management of both adults and children requiring cardiopulmonary bypass, and in management of patients with pheochromocytoma. 1-7 Phenoxybenzamine has been associated with more uniform body cooling and rewarming, and improved tissue perfusion during bypass.8 It is also known to increase cardiac output, stroke volume, and renal blood flow when given intravenously. 9 Specifically in pediatric open heart surgery, the combined use of phenoxybenzamine and dopamine provided a stable hemodynamic condition without a high total peripheral vascular resistance and stimulated postoperative diuresis. 9 Afterload reduction with parenteral phenoxybenzamine in neonates undergoing the Norwood procedure for hypoplastic left heart syndrome is associated with improved systemic oxygen delivery and stabilization of systemic vascular resistance.10 Furthermore, a strategy of reducing afterload with phenoxybenzamine and stabilizing the pulmonary to systemic flow ratio in this select population of patients has also been shown to improve operative survival. 11 We hypothesize that phenoxybenzamine will reduce afterload on the systemic ventricle in our selected patient population, thereby improving ventricular performance and decreasing the risks of pulmonary to systemic flow imbalance associated with current short-acting vasodilator therapy. We will plan to evaluate both physiologic variables as well as surgical outcomes in the selected study population.


Condition Intervention Phase
Congenital Heart Disease
Drug: Phenoxybenzamine
Other: Standard surgical approach
Phase II

MedlinePlus related topics: Heart Diseases
Drug Information available for: Phenoxybenzamine Phenoxybenzamine hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title: Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Our hypothesis is that the use of phenoxybenzamine in this select population will reduce initial postoperative lactate levels by a clinically-relevant level of 25%, relative to historical controls. [ Time Frame: To discharge ] [ Designated as safety issue: No ]

Estimated Enrollment: 62
Study Start Date: October 2008
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Group receiving phenoxybenzamine
Drug: Phenoxybenzamine
The drug will be administered in the operating room. After induction of anesthesia and the pIacement of appropriate cardiovascular monitoring lines, an initial loading dose of 0.25 mg/kg will be administered intravenously immediately prior to cardiopulmonary bypass.For up to 72 hours postoperatively, 0.25 mg/kg/day will be administered Based on published pharmacokinetic data these doses should block 90 -95% of alpha-peripheral receptors with a half life of 24 - 36 hours for regeneration.
2
Historical control
Other: Standard surgical approach
Historical controls

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 6 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Patient selection will be determined by an assessment of the risk of systemic ventricular dysfunction following open cardiac repair in a population of infants undergoing stage I palliation (Norwood procedure) for the diagnosis of either hypoplastic left heart syndrome or similar left-sided obstructive lesions in the setting of single-ventricle physiology. Eligible neonates and infants include those aged 0 days to 6 months. These patients will be evaluated on an individual basis and the decision to give phenoxybenzamine would be determined by the attending surgeon, anesthesiologist, and cardiologist.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00770705

Locations
United States, Tennessee
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: David P Bichell, MD Vanderbilt Children's Hospital
Principal Investigator: David P Bichell, MD Vanderbilt Children's Hospital
  More Information

Responsible Party: Vanderbilt Children's Hospital ( David P. Bichell MD/Principal Investigator )
Study ID Numbers: IRB#071183
Study First Received: October 9, 2008
Last Updated: October 9, 2008
ClinicalTrials.gov Identifier: NCT00770705  
Health Authority: United States: Food and Drug Administration

Study placed in the following topic categories:
Heart Diseases
Cardiovascular Abnormalities
Phenoxybenzamine
Congenital Abnormalities
Heart Defects, Congenital

Additional relevant MeSH terms:
Neurotransmitter Agents
Vasodilator Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Therapeutic Uses
Physiological Effects of Drugs
Adrenergic Antagonists
Cardiovascular Diseases
Adrenergic alpha-Antagonists
Cardiovascular Agents
Antihypertensive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009