Nesiritide Use Following Cardiac Surgery in Infants

Cardiopulmonary Bypass Clinical Trial

Official title:

Pilot Study of the Effects of Nesiritide on Hemodynamics and Urine Output Following Cardiopulmonary Bypass in Infants

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00281671
• Other study ID #: 05-12-160
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 8, 2006
• Est. completion date: October 2008

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 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 1 Year

Eligibility

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.

Related Conditions & MeSH terms

• Cardiopulmonary Bypass
• Congenital Abnormalities
• Heart Defects, Congenital

Intervention

Drug:
• nesiritide
nesiritide 0.015 mcg/kg/hour x 10 hours
• Placebo
0.9% sodium chloride infusion

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boston Children's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urine Output	Urine output measured in cc/kg/hour during the last 5 hours of the study drug infusion	5 hours
Secondary	Number of Participants With Hypotension and Bradycardia	Hypotension (mean arterial blood pressure < 40 mmHg for > 30 minutes) that is refractory to volume administration, increased inotropic/vasopressor support, and weaning of other vasodilators (e.g., milrinone) or sedatives; Bradycardia, defined as 1) a decrease in heart rate of more than 30 beats/minute from baseline following the initiation of study drug infusion that 2) results in new requirement for temporary atrial pacing or other treatment specifically to increase heart rate and 3) is not readily explainable by other conditions.	48 hours
Secondary	Urine Output		10 hours
Secondary	Cardiac Index	Cardiac index is based on the cardiac output, which is the amount of blood the left ventricle ejects into the systemic circulation in one minute, measured in liters per minute (l/min). Cardiac output is indexed to a patient's body size by dividing by the body surface area (m^2) to yield the cardiac index. Cardiac index was calculated in patients with an SVC catheter (previously placed for clinical indications) using the Fick principle using measured oxygen consumption (VO2), hemoglobin levels, and the difference between arterial and superior vena cava oxygen saturation. Oxygen consumption was measured using a real-time gas exchange technique with the Deltatrack II gas sensor.	Baseline (hour 0) and 6 hours after onset of study drug infusion