Effects of Perioperative Nesiritide or Milrinone Infusion on Recovery From Fontan Surgery
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ClinicalTrials.gov Identifier: NCT00543309 |
Recruitment Status
:
Terminated
(DSMB recommended termination based on interim outcomes analysis)
First Posted
: October 12, 2007
Last Update Posted
: November 4, 2013
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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 or disease | Intervention/treatment | Phase |
---|---|---|
Heart Defects, Congenital | Drug: nesiritide Drug: milrinone Drug: placebo | Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 106 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, 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 |
Study Start Date : | October 2007 |
Actual Primary Completion Date : | January 2013 |
Actual Study Completion Date : | July 2013 |

Arm | Intervention/treatment |
---|---|
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.
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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
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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.
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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
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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.
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Drug: placebo
Placebo bolus on CPB, then placebo infusion
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- Days alive and out of the hospital within 30 days of surgery. [ Time Frame: 30 days ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- Adverse events associated with nesiritide, milrinone or placebo use following Fontan surgery. [ Time Frame: Throughout hospitalization ]

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Ages Eligible for Study: | Child, Adult, Senior |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00543309
United States, Massachusetts | |
Children's Hospital Boston | |
Boston, Massachusetts, United States, 02115 |
Principal Investigator: | John M Costello, MD MPH | Boston Children’s Hospital |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | John M Costello, Associate in Cardiology, Children's Hospital, Boston |
ClinicalTrials.gov Identifier: | NCT00543309 History of Changes |
Other Study ID Numbers: |
0735070N |
First Posted: | October 12, 2007 Key Record Dates |
Last Update Posted: | November 4, 2013 |
Last Verified: | November 2013 |
Keywords provided by John M Costello, 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 |
Cardiotonic Agents Platelet Aggregation Inhibitors Vasodilator Agents Phosphodiesterase 3 Inhibitors Phosphodiesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Protective Agents |