Effects of Nesiritide in Pediatric Patients With Heart Failure

This study has been withdrawn prior to enrollment.
(Observational study that DSMB placed on hold (withdrew 4 subjects). Protocol revised and received IND to become interventional PK study (no subjects enrolled).)
Sponsor:
Collaborator:
Children's Healthcare of Atlanta
Information provided by (Responsible Party):
Janet Simsic, MD, Emory University
ClinicalTrials.gov Identifier:
NCT00166010
First received: September 12, 2005
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

Children with severe heart failure need immediate appropriate care. New and better drugs are constantly being developed. As these drugs are approved for adult use, they are used off-label for children. The Food and Drug Administration (FDA) encourages clinical studies of drugs in children to further extend appropriate use of new medicines.

This study involves nesiritide, which was approved as a congestive heart failure treatment in adults in August 2001. The investigators' use of this drug in a pediatric population with severe heart failure has been encouraging. The investigators now wish to formally determine the pharmacokinetic and safety of Nesiritide in children.

The investigators will enroll 30 patients who are in the cardiac intensive care unit with severe heart failure. The data collected will include weights, vital signs, laboratory results, and echocardiography results. A research lab test called B-type natriuretic peptide (BNP) will be done several times during this study. If the patient still has an intravenous (IV) catheter, the blood sample will be taken from the IV. If the patient does not have an IV, the sample will be taken from a fingerstick.

The duration of the study will be the first 2 days of the patient's stay in the cardiac intensive care unit and thru discharge to evaluate the endpoint safety of Nesiritide. Additional information will also be collected if patient gets re-admitted within 30 days of discharge.


Condition Intervention
Heart Failure
Ventricular Dysfunction
Heart Decompensation
Drug: Nesiritide

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-center, Pharmacokinetic Evaluation of Nesiritide in the Pediatric Population With Heart Failure

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • To determine pharmacokinetics and safety of nesiritide in children [ Time Frame: study period - first 2 days stay in cardiac intensive care unit thru hospital discharge and re-admission within 30 days of discharge. ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: October 2004
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nesiritide Drug: Nesiritide
Standard dose of nesiritide which is a loading dose of 1 mcg/kg IV over 30 minutes followed by a nesiritide infusion at 0.01mcg/kg/min. All patients will be continually evaluated. At any time the attending physician may add or adjust treatment if deemed clinically indicated.

Detailed Description:

Nesiritide (human recombinant B-type natriuretic peptide) has been recently approved by the Food and Drug Administration for the intravenous treatment of patients with decompensated congestive heart failure. Nesiritide has been studied in a broad range of patients, including the elderly, women, and African Americans, and patients with a history of various cardiovascular conditions including hypertension, diabetes, post myocardial infarction, atrial fibrillation/flutter, nonsustained ventricular tachycardia, left ventricular diastolic dysfunction, and acute coronary syndrome. However, clinical experience in the pediatric population has been limited.

Nesiritide is a human B-type natriuretic peptide (BNP) produced by recombinant technology having the same amino acid sequence as the naturally occurring human BNP. BNP is predominantly secreted by the cardiac ventricles in response to increased cardiac volume and pressure overload. Its pharmacologic effects include hemodynamic, neurohormonal, and renal. In adult studies, hemodynamic effects are characterized by balanced venous and arterial dilation, resulting in decreased preload and afterload demonstrated by a reduction of pulmonary capillary wedge pressure, pulmonary arterial pressure, and systemic vascular resistance while neurohormonal effects of nesiritide favorably inhibit the renin-angiotension-aldosterone system, leading to decreased plasma aldosterone and norepinephrine levels. The renal effects most often seen with nesiritide use is increased urine output and lower diuretic utilization.

There are currently no published articles discussing the use, including pharmacokinetics, of nesiritide in children. However, there are several centers that are currently using the drug - Columbus, Missouri; San Diego, California; Charleston, South Carolina; Loma Linda, California. Our experience in the infant after cardiac surgery and the older child with heart failure is encouraging. In children receiving nesiritide therapy, we noted significant clinical improvement with no appreciable side effects. Based on our initial experience, further prospective studies need to be performed in order to determine the pharmacokinetics and safety of using this therapy in the pediatric cohort.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age newborn to 18 years.
  2. Patients admitted to the CICU at Children's Healthcare of Atlanta in heart failure defined as decreased cardiac function and/or volume overload or admitted to the CICU at Children's Healthcare of Atlanta post-operatively after congenital heart defect repair surgery with increasing filling pressures and decreased ventricular compliance as seen by intracardiac line monitoring and echocardiography.
  3. Receiving or about to receive nesiritide as medical therapy.
  4. Informed consent will be signed by parent or guardian for all patients. (assent if applicable).

Exclusion Criteria:

  1. Patients requiring extra corporeal membrane oxygenation (ECMO) support.
  2. Patients requiring central veno-venous hemofiltration (CVVH).
  3. Patients that are pregnant
  4. Parent or legal guardian (or patient when applicable) refuses to sign informed consent.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00166010

Sponsors and Collaborators
Emory University
Children's Healthcare of Atlanta
Investigators
Principal Investigator: Janet M Simsic, MD Emory University
  More Information

Publications:
Responsible Party: Janet Simsic, MD, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT00166010     History of Changes
Other Study ID Numbers: IRB00003353
Study First Received: September 12, 2005
Last Updated: June 3, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Emory University:
drug
pediatrics
cardiac
Children with Cardiac Ventricular Failure

Additional relevant MeSH terms:
Heart Failure
Ventricular Dysfunction
Heart Diseases
Cardiovascular Diseases
Natriuretic Peptide, Brain
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014