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

This study has been terminated.
(DSMB recommended termination based on interim outcomes analysis)
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
John M Costello, Children's Hospital, Boston
ClinicalTrials.gov Identifier:
NCT00543309
First received: October 10, 2007
Last updated: November 1, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Heart Defects, Congenital
Drug: nesiritide
Drug: milrinone
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Impact of Empiric Nesiritide or Milrinone Infusion on Early Postoperative Recovery Following Fontan Surgery: a Randomized, Double-blind, Placebo-controlled Clinical Trial

Resource links provided by NLM:


Further study details as provided by Children's Hospital Boston:

Primary Outcome Measures:
  • Days alive and out of the hospital within 30 days of surgery. [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 180 days ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Neurohumoral profile following Fontan surgery: plasma aldosterone, norepinephrine, epinephrine, renin, endothelin-1 and vasopressin levels from preoperative baseline to postoperative CICU hour 1. [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Adverse events associated with nesiritide, milrinone or placebo use following Fontan surgery. [ Time Frame: Throughout hospitalization ] [ Designated as safety issue: Yes ]

Enrollment: 106
Study Start Date: October 2007
Study Completion Date: July 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: I- nesiritide
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.
Drug: nesiritide
Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted
Other Name: Natrecor
Active Comparator: II- Milrinone
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.
Drug: milrinone
Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted
Other Name: Primacor
Placebo Comparator: III- placebo
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.
Drug: placebo
Placebo bolus on CPB, then placebo infusion

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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00543309

Locations
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
John M Costello
American Heart Association
Investigators
Principal Investigator: John M Costello, MD MPH Children's Hospital Boston
  More Information

No publications provided

Responsible Party: John M Costello, Associate in Cardiology, Children's Hospital, Boston
ClinicalTrials.gov Identifier: NCT00543309     History of Changes
Other Study ID Numbers: 0735070N
Study First Received: October 10, 2007
Last Updated: November 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital Boston:
Fontan Operation
Cardiopulmonary Bypass
Heart Defects, Congenital
Milrinone
Natriuretic peptide, brain

Additional relevant MeSH terms:
Heart Defects, Congenital
Congenital Abnormalities
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Natriuretic Peptide, Brain
Milrinone
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Cardiotonic Agents
Platelet Aggregation Inhibitors
Hematologic Agents
Vasodilator Agents
Phosphodiesterase 3 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on August 28, 2014