Effects of Perioperative Nesiritide or Milrinone Infusion on Recovery From Fontan Surgery
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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 |
- Days alive and out of the hospital within 30 days of surgery. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
- 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 |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00543309
| United States, Massachusetts | |
| Children's Hospital Boston | |
| Boston, Massachusetts, United States, 02115 | |
| 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 Milrinone Natriuretic Peptide, Brain Cardiotonic Agents Cardiovascular Agents Enzyme Inhibitors Hematologic Agents |
Molecular Mechanisms of Pharmacological Action Natriuretic Agents Pharmacologic Actions Phosphodiesterase 3 Inhibitors Phosphodiesterase Inhibitors Physiological Effects of Drugs Platelet Aggregation Inhibitors Protective Agents Therapeutic Uses Vasodilator Agents |
ClinicalTrials.gov processed this record on February 27, 2015