Effects of Perioperative Nesiritide or Milrinone Infusion on Recovery From Fontan Surgery
Summary
The staged surgical pathway to treat children with single ventricle heart defects culminates with the Fontan operation. In this procedure, systemic venous return is rerouted directly to the pulmonary arteries, which serves to separate the systemic and pulmonary circulations. Although mortality following the Fontan operation is now uncommon, early postoperative morbidity including prolonged postoperative chest tube drainage and hospitalization remains significant. The efficacy of empiric inotropic, vasodilator and neurohumoral-inhibitory therapies in the perioperative period is unknown and practice varies widely between centers.
The investigators will propose a single-center, randomized, double-blind, phase II clinical trial in children undergoing Fontan surgery. The investigators plan to compare the effects of perioperative nesiritide, milrinone and placebo infusions on the early postoperative clinical course and neurohumoral profile. The investigators hypothesize that, when compared to the milrinone and placebo groups, the nesiritide group will have more days alive and out of the hospital within the first 30 days after surgery.
Description
The staged surgical pathway to treat children with single ventricle heart defects culminates with the Fontan operation. In this procedure, systemic venous return is rerouted directly to the pulmonary arteries, which serves to separate the systemic and pulmonary circulations. Following this operation, deoxygenated blood flows passively from the body through the lungs without a pumping chamber. Although mortality following the Fontan operation is now uncommon, early postoperative morbidity including prolonged postoperative chest tube drainage and hospitalization remains significant. The efficacy of empiric inotropic, vasodilator and neurohumoral-inhibitory therapies in the perioperative period is unknown and practice varies widely between centers.
We propose a single-center, randomized, double-blind, phase II clinical trial in children undergoing Fontan surgery. We plan to compare the effects of perioperative nesiritide, milrinone and placebo infusions on the early postoperative clinical course and neurohumoral profile. The primary aim of the study is to determine whether nesiritide, milrinone or placebo infusion is associated with fewer days alive and out of the hospital within 30 days of surgery. We hypothesize that, when compared to the milrinone and placebo groups, the nesiritide group will have more days alive and out of the hospital within the first 30 days after surgery. Secondary aims are to determine the effects of these infusions on postoperative resource consumption, hemodynamics, arrhythmias, renal function, neurohumoral activation and adverse events. Thirty-nine patients per group (117 total patients) will be enrolled over three years.
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Conditions
Heart Defects, Congenital
Intervention
nesiritide, milrinone, placebo
Location
Children's Hospital Boston
Boston
Massachusetts
United States
02115
Status
Recruiting
Source
Children's Hospital Boston
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00543309
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Heart Defects, Congenital
Developmental abnormalities involving structures of the heart. These defects are present at birth but may be discovered later in life.
Endocardial Fibroelastosis
A condition characterized by the thickening of ENDOCARDIUM due to proliferation of fibrous and elastic tissue, usually in the left ventricle leading to impaired cardiac function (CARDIOMYOPATHY, RESTRICTIVE). It is most commonly seen in young children and rarely in adults. It is often associated with congenital heart anomalies (HEART DEFECTS CONGENITAL;) INFECTION; or gene mutation. Defects in the tafazzin protein, encoded by TAZ gene, result in a form of autosomal dominant familial endocardial fibroelastosis.
Ventricular Outflow Obstruction
Occlusion of the outflow tract in either the LEFT VENTRICLE or the RIGHT VENTRICLE of the heart. This may result from CONGENITAL HEART DEFECTS, predisposing heart diseases, complications of surgery, or HEART NEOPLASMS.
Trilogy Of Fallot
A combination of congenital heart defects consisting of three key features including ATRIAL SEPTAL DEFECTS; PULMONARY STENOSIS; and RIGHT VENTRICULAR HYPERTROPHY.
Endocarditis, Bacterial
Inflammation of the ENDOCARDIUM caused by BACTERIA that entered the bloodstream. The strains of bacteria vary with predisposing factors, such as CONGENITAL HEART DEFECTS; HEART VALVE DISEASES; HEART VALVE PROSTHESIS IMPLANTATION; or intravenous drug use.
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PubMed Articles
The role of milrinone in children with cardiovascular compromise: review of the literature.
BACKGROUND: Cardiovascular instability is a common complication in children after cardiac surgery and in various forms of shock. METHODS: Systematic literature review. RESULTS: Four randomized control...
Congenital heart defects are diagnosed in approximately 1% of births in the United States and account for the largest proportion of infant mortality attributable to birth defects. Congenital heart def...
INTRODUCTION: The present study determined whether late-ischemia/early reperfusion therapy with the β(1)-adrenergic receptor (AR) blocker esmolol and phosphodiesterase III inhibitor milrinone reduced...
Acute Effects of Intravenous Nesiritide on Cardiac Contractility in Heart Failure.
BACKGROUND: Although nesiritide is a potent vasodilator, studies using myocytes and isolated muscle strips have shown that recombinant B-type natriuretic peptide (BNP; nesiritide) decreases contractil...
Levosimendan in Congenital Cardiac Surgery: A Randomized, Double-Blind Clinical Trial.
OBJECTIVE:: In this study, the authors used a continuous infusion of either levosimendan or milrinone as inotropic support after corrective congenital cardiac surgery. The hemodynamic and biochemical...
