Effects of Perioperative Nesiritide or Milrinone Infusion on Recovery From Fontan Surgery

John M Costello

Status and phase: Terminated; Phase 2

Conditions: Heart Defects, Congenital

Treatments: Drug: nesiritide; Drug: placebo; Drug: milrinone

Study type: Interventional

Funder types: Other

Identifiers

NCT00543309

0735070N

Details and patient eligibility

About

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.

Full 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.

Enrollment: 106 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients undergoing an elective, primary Fontan operation at Children's Hospital Boston.

Exclusion criteria

• Revision surgery for failing Fontan circulation.
• Preoperative serum creatinine > 1.5 mg/dL or chronic dialysis.
• The attending surgeon, cardiac anesthesiologist, or cardiac intensivist has a compelling indication to initiate either nesiritide or milrinone outside of the confines of the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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106 participants in 3 patient groups, including a placebo group

I- nesiritide

Experimental group

Description:

Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met.

Treatment:

Drug: nesiritide

II- Milrinone

Active Comparator group

Description:

Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met.

Treatment:

Drug: milrinone

III- placebo

Placebo Comparator group

Description:

Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met.

Treatment:

Drug: placebo