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

Condition(s) targeted: Heart Defects, Congenital

Intervention: nesiritide (Drug); milrinone (Drug); placebo (Drug)

Phase: Phase 2

Status: Terminated

Sponsored by: John M Costello

Official(s) and/or principal investigator(s):
John M Costello, MD MPH, Principal Investigator, Affiliation: Children's Hospital Boston

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.

Official title: Impact of Empiric Nesiritide or Milrinone Infusion on Early Postoperative Recovery Following Fontan Surgery: a Randomized, Double-blind, Placebo-controlled Clinical Trial

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Days alive and out of the hospital within 30 days of surgery.

Secondary outcome:

Convalescence from Fontan surgery: days of intensive care; hours of mechanical ventilation; days of chest tube drainage; direct costs of hospitalization; number of days alive and out of the hospital within 180 days of surgery.

Hemodynamics following Fontan surgery: CI at postop. hours 1, 8; CVP, peak lactate level, inotropic score, troponin I level and net fluid balance within 24 hours of CICU admit; incidence of tachyarrhythmias during the first 120 hours of CICU admission.

Renal function following Fontan surgery: Urine output during first 24 hours of postoperative CICU admit; diuretic requirements for the first 120 postoperative hours; maximal change in serum creatinine and creatinine clearance up to 14 days after surgery.

Neurohumoral profile following Fontan surgery: plasma aldosterone, norepinephrine, epinephrine, renin, endothelin-1 and vasopressin levels from preoperative baseline to postoperative CICU hour 1.

Adverse events associated with nesiritide, milrinone or placebo use following Fontan surgery.

Detailed 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.

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Children's Hospital Boston, Boston, Massachusetts 02115, United States

Starting date: October 2007
Last updated: November 1, 2013