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

Heart Defects, Congenital Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00543309
• Other study ID #: 0735070N
• Status: Terminated
• Phase: Phase 2
• Start date: October 2007
• Est. completion date: July 2013

Study information

• Verified date: May 2018
• Source: Boston Children’s Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 106
• Est. completion date: July 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Congenital Abnormalities
• Heart Defects, Congenital

Intervention

Drug:
• nesiritide
Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted
• milrinone
Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted
• placebo
Placebo bolus on CPB, then placebo infusion

Locations

Country	Name	City	State
United States	Children's Hospital Boston	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
John M Costello	American Heart Association

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 random — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Days Alive and Out of the Hospital Within 30 Days of Surgery.		30 days
Secondary	Cardiovascular: Cardiac Index	Cardiac index measured using Fick principle with measured oxygen consumption.	Postoperative hour #1
Secondary	Cardiovascular: Cardiac Index	Cardiac index measured using Fick principle with measured oxygen consumption.	Postoperative hour #8
Secondary	Cardiovascular: Arrhythmia	arrhythmia lasting >30 seconds or requiring treatment	Postoperative day (POD) #0 through 5
Secondary	Cardiovascular: Peak Inotrope Score	Peak Inotrope Score = Doses of dopamine in mcg/kg/minute + dobutamine in mcg/kg/minute + (epinephrine in mcg/kg/minute x 100).; The lowest (best) possible Peak Inotrope Score = 0 dose equivalents. There is no maximum Peak Inotrope Score.	Initial 24 hours in CICU
Secondary	Cardiovascular: Peak Lactate Level		Initial 24 hours in CICU
Secondary	Renal Function: Urine Output	Volume of urine in mL/kg per day	first 24 hours CICU admit
Secondary	Renal Function: Maximum Change in Serum Creatinine		14 days after surgery
Secondary	Resource Utilization: Hours of Mechanical Ventilation Until Initial Extubation	Hours of mechanical ventilation until initial extubation following the Fontan operation.	From Fontan operation until initial extubation, assessed during initial CICU stay, up to 30 days.
Secondary	Resource Utilization: Days of Initial CICU Stay	Days of initial postoperative CICU care following the Fontan operation.	From Fontan operation until initial discharge from the CICU, assessed during the postoperative hospitalization, up to 90 days.
Secondary	Resource Utilization: Chest Tube Days	Days during which one or more chest tubes were in place following the Fontan operation.	From Fontan operation until final chest tube removed, assessed during postoperative hospitalization, up to 90 days.
Secondary	Resource Utilization: Days Alive and Out of Hospital Within 180 Days of Surgery	Days the patient was alive and out of hospital within the 180 days after Fontan surgery	180 days
Secondary	Plasma Norepinephrine Levels.	Plasma norepinephrine levels measured at preoperative baseline and postoperative CICU hour 1, 8, 24.	Preoperative baseline to 24 hours after CICU admission
Secondary	Epinephrine Levels	Plasma epinephrine levels measured at preoperative baseline and postoperative CICU hour 1, 8, 24.	Preoperative baseline to 24 hours after CICU admission
Secondary	N-terminal Pro-brain Natriuretic Peptide Levels	N-terminal pro-brain natriuretic peptide levels measured at preoperative baseline and postoperative CICU hour 1, 8, 24.	Preoperative baseline to 24 hours after CICU admission