Do Elevated BNP Levels Predict Hemodynamically Significant PDAs

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01497054
Recruitment Status : Completed
First Posted : December 22, 2011
Last Update Posted : July 4, 2013
Alere, Inc.
Information provided by (Responsible Party):
Kate Tauber, Albany Medical College

Brief Summary:
The purpose of this study is to determine if B type natriuretic peptide (BNP) levels can be used to predict a hemodynamically significant patent ductus arteriosus (PDA). This peptide is produced by the ventricles in the heart when they are under stress, such as when a ductus remains open. If we can use a simple and inexpensive blood test to determine whether a PDA needs to be treated, we can potentially treat infants sooner than if they needed to wait for the availability of a cardiologist to perform an echocardiogram. This might decrease some of the deleterious effects of PDAs on the preterm infant such as bronchopulmonary dysplasia, necrotizing enterocolitis, renal hypoperfusion, and pulmonary hemorrhage. In a situation where follow up echocardiogram after a course of medical therapy shows persistent PDA, this test may help to decide whether this baby needs further treatment, either medical or surgical.

Condition or disease
Patent Ductus Arteriosus

Detailed Description:

B type natriuretic peptide (BNP) is mainly synthesized in the ventricles of the heart and released in response to volume and pressure loading and ventricular stress and, therefore, plays an important role in regulation of extracellular fluid volume. BNP causes diuresis, natriuresis, arterial and venous vasodilation and antagonizes the renin-angiotensin system resulting in a reduction in intravascular volume and decreased ventricular preload and afterload.

In adults, BNP levels have been routinely used to diagnose and measure the degree of congestive heart failure. In healthy term infants, BNP levels are initially elevated in the first few days of life but then decline over the ensuing week after birth to near adult levels by 3 months of age. However, in premature newborn infants there are still no normative values for BNP and, therefore, no agreed-upon cut off points to diagnose ventricular overload without confirmatory echocardiography. Patent ductus arteriosus (PDA) is the most common cause of ventricular overload and congestive heart failure in premature neonates and can be a cause of significant morbidity. Excessive pulmonary blood flow due to the aortopulmonary shunting can result in increased ventilatory dependency and thereby contribute to chronic lung disease. Other possible sequelae from a PDA include renal hypoperfusion, necrotizing entercolitis, and pulmonary hemorrhage. Early closure of a PDA has been shown to reduce these risks.

Delayed ductal closure is inversely related to GA at birth with the incidence varying from 20% in babies greater than 32 weeks gestation and up to 60% in babies less than 28 weeks gestation. Currently, infants are screened for a PDA by echocardiography. This requires that centers have access to cardiologists to perform and analyze these studies. A simple blood test that could help diagnose a hemodynamically significant PDA would be extremely helpful in low birth weight infants, especially in more remote centers that do not have routine access to cardiology services. To date, there is no accepted blood test although numerous studies are emerging suggesting that BNP might be such a test. It has been shown that the magnitude of shunting through a PDA is a major determinant of BNP level, however, the levels published in various studies for what is hemodynamically significant varies greatly. In addition, the studies that have been done previously are on small sample sizes (less than 70 patients, with one retrospective study that had 88 patients) and on various gestational ages and, therefore, it is difficult to extrapolate normative data.

It is already known that BNP levels are elevated in neonates with a hsPDA, however, there is little agreement on how high a BNP level needs to get to imply a hsPDA. We propose a study to measure the BNP values in all infants born less than 32 weeks gestation with and without a PDA. We will also do serial BNP levels with concurrent echocardiograms in infants with a PDA to determine a cutoff value of BNP above which an infant is likely to have a hsPDA. We hope that our study, with a larger sample size and on all infants with and without a PDA, will be able to not only gather more definitive data on what the cutoff BNP level is, but also gather normative BNP data on premature infants without PDAs.

Study Type : Observational
Actual Enrollment : 109 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Diagnostic Prediction Value of B Type Natriuretic Peptide (BNP) Levels in Hemodynamically Significant Patent Ductus Arteriosus (hsPDA) in Premature Infants.
Study Start Date : December 2011
Actual Primary Completion Date : April 2013
Actual Study Completion Date : April 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. BNP level and size of PDA [ Time Frame: within first 2 weeks of life ]
    BNP levels measured at several time points during first 2 weeks of life and compared to findings on echocardiogram to see if size of PDA correlated with BNP level.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 24 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Preterm infants between 24 0/7 weeks gestation and 31 6/7 weeks gestation.

Inclusion Criteria:

  • gestational age between 24 0/7 weeks gestation and 31 6/7 weeks gestation. - Infants must be enrolled by 24 hours of life.

Exclusion Criteria:

  • congenital heart disease,
  • necrotizing enterocolitis,
  • culture positive sepsis or culture negative but treated for presumed sepsis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01497054

United States, New York
Albany Medical Center Neonatal Intesive Care Unit
Albany, New York, United States, 12208
Sponsors and Collaborators
Albany Medical College
Alere, Inc.
Principal Investigator: Kate A Tauber, MD Albany Medical College
Study Director: Upender K Munshi, MD Albany Medical College
Study Director: Robin Doyle, MD Capital Distric Pediatric Cardiology, affiliated with Albany Medical Center

Responsible Party: Kate Tauber, Principal Investigator, Albany Medical College Identifier: NCT01497054     History of Changes
Other Study ID Numbers: 3155
First Posted: December 22, 2011    Key Record Dates
Last Update Posted: July 4, 2013
Last Verified: December 2011

Keywords provided by Kate Tauber, Albany Medical College:
B type natriuretic peptide
Patent Ductus Arteriosus
Preterm infant

Additional relevant MeSH terms:
Ductus Arteriosus, Patent
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Natriuretic Peptide, Brain
Natriuretic Agents
Physiological Effects of Drugs