Clinical trial NCT00543309: Effects of Perioperative Nesiritide or Milrinone Infusion on Recovery From Fontan 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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Heart Defects, Congenital
Keywords: Fontan Operation
Cardiopulmonary Bypass
Heart Defects, Congenital
Milrinone
Natriuretic peptide, brain
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2007-10-12
Enrollment: 106
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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.

Primary outcomes:
measure: Days Alive and Out of the Hospital Within 30 Days of Surgery.
timeFrame: 30 days
Secondary outcomes:
measure: Cardiovascular: Cardiac Index
timeFrame: Postoperative hour #1
measure: Cardiovascular: Cardiac Index
timeFrame: Postoperative hour #8
measure: Cardiovascular: Arrhythmia
timeFrame: Postoperative day (POD) #0 through 5
measure: Cardiovascular: Peak Inotrope Score
timeFrame: Initial 24 hours in CICU
measure: Cardiovascular: Peak Lactate Level
timeFrame: Initial 24 hours in CICU
measure: Renal Function: Urine Output
timeFrame: first 24 hours CICU admit
measure: Renal Function: Maximum Change in Serum Creatinine
timeFrame: 14 days after surgery
measure: Resource Utilization: Hours of Mechanical Ventilation Until Initial Extubation
timeFrame: From Fontan operation until initial extubation, assessed during initial CICU stay, up to 30 days.
measure: Resource Utilization: Days of Initial CICU Stay
timeFrame: From Fontan operation until initial discharge from the CICU, assessed during the postoperative hospitalization, up to 90 days.
measure: Resource Utilization: Chest Tube Days
timeFrame: From Fontan operation until final chest tube removed, assessed during postoperative hospitalization, up to 90 days.
measure: Resource Utilization: Days Alive and Out of Hospital Within 180 Days of Surgery
timeFrame: 180 days
measure: Plasma Norepinephrine Levels.
timeFrame: Preoperative baseline to 24 hours after CICU admission
measure: Epinephrine Levels
timeFrame: Preoperative baseline to 24 hours after CICU admission
measure: N-terminal Pro-brain Natriuretic Peptide Levels
timeFrame: Preoperative baseline to 24 hours after CICU admission
Other outcomes:
Locations:
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: John M Costello, MD MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Costello JM, Dunbar-Masterson C, Allan CK, Gauvreau K, Newburger JW, McGowan FX Jr, Wessel DL, Mayer JE Jr, Salvin JW, Dionne RE, Laussen PC. Impact of empiric nesiritide or milrinone infusion on early postoperative recovery after Fontan surgery: a randomized, double-blind, placebo-controlled trial. Circ Heart Fail. 2014 Jul;7(4):596-604. doi: 10.1161/CIRCHEARTFAILURE.113.001312. Epub 2014 Jun 6.