Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery

NCT00770705 | Withdrawn Phase 2 DMC

• 1 other identifier: IRB#071183
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Congenital Heart Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  To discharge

Study Arms (2)

1

EXPERIMENTAL

Group receiving phenoxybenzamine

Drug: Phenoxybenzamine

2

OTHER

Historical control

Other: Standard surgical approach

Interventions

Phenoxybenzamine DRUG

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.

1

Standard surgical approach OTHER

Historical controls

2

Eligibility Criteria

• Age: Up to 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt Children's Hospital

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Heart Defects, Congenital

Interventions

Phenoxybenzamine

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Ethylamines; Amines; Organic Chemicals

Study Officials

• David P Bichell, MD

  Vanderbilt Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiac Surgery Professor and Pediatric Cardiac Surgery Chief

Study Record Dates

• First Submitted: October 9, 2008
• First Posted: October 10, 2008
• Study Start: October 1, 2008
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: May 1, 2017

Record last verified: 2017-04

Locations

US (1)