Clinical trial NCT00281671: Nesiritide Use Following Cardiac Surgery in Infants
Official title: Pilot Study of the Effects of Nesiritide on Hemodynamics and Urine Output Following Cardiopulmonary Bypass in Infants
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Heart Defects, Congenital
Cardiopulmonary Bypass
Keywords: Nesiritide
Natriuretic Peptide, Brain
Heart Defects, Congenital
Cardiopulmonary Bypass
Diuretics
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2006-01-25
Enrollment: 9
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effects of nesiritide on urine output and hemodynamics following cardiopulmonary bypass in infants. Safety and pharmacokinetic data will also be obtained.

Detailed description: Nesiritide, a recombinant human B-type natriuretic peptide, has vasodilatory, lusitropic and diuretic properties in healthy humans, and improves hemodynamics and symptoms in adults with decompensated congestive heart failure. Several retrospective case series suggest that nesiritide has beneficial effects on hemodynamics and urine output in adults and children following cardiac surgery.

The purpose of this prospective, randomized, double-blind, crossover study is to evaluate the effects of a continuous infusion of nesiritide on postoperative hemodynamics and urine output in infants with congenital heart disease who undergo cardiac surgery requiring cardiopulmonary bypass (CPB). Patients less than 1 year of age following cardiac surgery will be eligible for the study if they have received two conventional diuretics (furosemide and chlorothiazide) for at least 12 hours, yet are not effectively achieving a negative fluid balance, thus prohibiting sternal closure or tracheal extubation. Patients will be randomized to receive either a 10-hour infusion of nesiritide, a two hour washout period, followed by a 10-hour infusion of placebo, or this study drug sequence in reverse order. During the 24-hour study period, serial cardiac output measurements and BNP levels will be obtained, vital signs and intracardiac filling pressures will be recorded, and urine output will be measured.

Eligibility criteria: Inclusion Criteria:

* \> 48 hours after cardiac surgery requiring cardiopulmonary bypass
* \< 1 year of age
* Receiving chlorothiazide and furosemide for \> 12 hours
* Urine output \< 4 cc/kg/hour, or fluid intake \> output for 2 consecutive days
* Receiving mechanical ventilation
* Presence of body wall edema on CXR, defined as a radiologic index of \> 2
* Plan for \> 24 hrs further diuresis before chest closure or extubation

Exclusion Criteria:

* Age \> 365 days at the time of enrollment
* Corrected estimated gestational age \< 35 weeks at the time of enrollment
* Serum creatinine \> 2.0 mg/dL at the time of enrollment
* Significant hemodynamic instability at the time of enrollment
* Lack of dedicated intravenous access for nesiritide infusion
* Lack of arterial line for continuous blood pressure monitoring
* Lack of a Foley catheter for continuous urine collection
* Enrollment in another research study such that the outcomes of either study may be confounded by participation in this study, or such that the amount of blood drawn for research purposes becomes excessive.

Primary outcomes:
measure: Urine Output
timeFrame: 5 hours
Secondary outcomes:
measure: Number of Participants With Hypotension and Bradycardia
timeFrame: 48 hours
measure: Urine Output
timeFrame: 10 hours
measure: Cardiac Index
timeFrame: Baseline (hour 0) and 6 hours after onset of study drug infusion
Other outcomes:
Locations:
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
Study officials:
affiliation: Department of Cardiology, Children's Hospital Boston
name: John M Costello, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Costello JM, Backer CL, Checchia PA, Mavroudis C, Seipelt RG, Goodman DM. Effect of cardiopulmonary bypass and surgical intervention on the natriuretic hormone system in children. J Thorac Cardiovasc Surg. 2005 Sep;130(3):822-9. doi: 10.1016/j.jtcvs.2005.03.008.
citation: Costello JM, Backer CL, Checchia PA, Mavroudis C, Seipelt RG, Goodman DM. Alterations in the natriuretic hormone system related to cardiopulmonary bypass in infants with congestive heart failure. Pediatr Cardiol. 2004 Jul-Aug;25(4):347-53. doi: 10.1007/s00246-003-0512-5.
citation: Mahle WT, Cuadrado AR, Kirshbom PM, Kanter KR, Simsic JM. Nesiritide in infants and children with congestive heart failure. Pediatr Crit Care Med. 2005 Sep;6(5):543-6. doi: 10.1097/01.pcc.0000164634.58297.9a.
citation: Simsic JM, Reddy VS, Kanter KR, Kirshbom PM, Forbess JM. Use of nesiritide (human B-type natriuretic peptide) in infants following cardiac surgery. Pediatr Cardiol. 2004 Nov-Dec;25(6):668-70. doi: 10.1007/s00246-003-0680-3.