Nesiritide Use Following Cardiac Surgery in Infants

August 19, 2020 updated by: John M Costello, Boston Children's Hospital

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital Boston

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 1 year (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
In this crossover pilot study, patients are randomly assigned to receive either nesiritide or placebo infusion for 10 hours, followed by a two hour washout period, and then the other study drug for 10 hours.
Drug: Placebo
0.9% sodium chloride infusion
Other Names:
  • 0.9% sodium chloride infusion
Experimental: Nesiritide
In this crossover pilot study, patients are randomly assigned to receive either nesiritide or placebo infusion for 10 hours, followed by a two hour washout period, and then the other study drug for 10 hours.
Drug: nesiritide
nesiritide 0.015 mcg/kg/hour x 10 hours
Other Names:
  • Natrecor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urine Output
Time Frame: 5 hours
Urine output measured in cc/kg/hour during the last 5 hours of the study drug infusion
5 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Hypotension and Bradycardia
Time Frame: 48 hours

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
Urine Output
Time Frame: 10 hours
10 hours
Cardiac Index
Time Frame: Baseline (hour 0) and 6 hours after onset of study drug infusion
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boston Children's Hospital

Investigators

  • Principal Investigator: John M Costello, MD, Department of Cardiology, Children's Hospital Boston

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 8, 2006

Primary Completion (Actual)

October 1, 2008

Study Completion (Actual)

October 1, 2008

Study Registration Dates

First Submitted

January 23, 2006

First Submitted That Met QC Criteria

January 23, 2006

First Posted (Estimate)

January 25, 2006

Study Record Updates

Last Update Posted (Actual)

August 27, 2020

Last Update Submitted That Met QC Criteria

August 19, 2020

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05-12-160

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

Email PI for data requests.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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