Nesiritide and Renal Function After the Total Artificial Heart

NCT ID: NCT01836809

Last Updated: 2016-02-08

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-30

Study Completion Date

2014-05-31

Brief Summary

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The prevalence of renal dysfunction after implantation of the artificial heart is high. The infusion of exogenous B-type natriuretic peptide (BNP) after implantation of the total artificial heart (TAH) improves renal function in a sustained manner. The renal protective and hormone-modulating effects of nesiritide may be enhanced with ventriculectomy compared to heart failure surgery that leaves the native myocardium intact. The goal of this project is to determine the renal protective effects of nesiritide after implantation of a mechanical device.

Detailed Description

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This is a randomized, double blinded placebo controlled study that will take place in the Cardiac Surgery Intensive Care Unit, at Virginia Commonwealth University (VCU) Hospital Center.

This study will enroll 20 adult patients who have undergone implantation of a circulatory support device (10 TAH patients, 10 Left ventricular assist device (LVAD) patients). Patients will receive standard postoperative care, including anticoagulation, continuous hemodynamic monitoring with an arterial line and central venous line and hemodynamic support as determine by the cardiac surgery clinical team. We will exclude patients who are receiving renal replacement therapy at the time of device implantation or those that have had previous solid organ transplantation in order to remove the confounding influence of calcineurin inhibitor exposure on renal function. Patient unable to provide informed consent will also be excluded.

Nesiritide Infusion

The patients will be randomized (stratified by device type) to either the study drug (nesiritide at 0.005 mcg/kg/min without a bolus) or placebo. A fixed-dose infusion will be initiated 6 hours after the patients having come off of cardiopulmonary bypass and continued for 48 hours.

Laboratory Measurements

Acute and chronic effects of nesiritide on Glomerular Filtration Rate (GFR) and Renal Plasma Flow (RPF) will be measured by continuous infusion of iothalamate (IOTH) and phenylalanine hydroxylase (PAH), respectively. GFR and RPF will be measured at baseline (-3 to 0 hrs) and at 3 intervals during drug/placebo administration as follows: 0 to 6, 6 to 16 and 16 to 40. Intravenous catheters will be placed as needed for infusion of PAH and IOTH and for timed blood collections.

Urine volume, creatinine, sodium excretion will also be measured. Neurohormones will be measured at all time points 3-6. Plasma renin activity will be measured with an automated chemiluminescent immunoassay (DiaSorin Liaison). Serum aldosterone concentration will be determined by liquid chromatography-mass spectrometry (Agilent, AB Sciex API 5000). Serum BNP concentration will be measured with a sandwich chemiluminescent immunoassay (Siemens Healthcare Diagnostics, ADVIA Centaur BNP immunoassay).

Statistical Analysis Sample size was determined using urine output data from our preliminary observations. Power calculations showed that a total of 10 patients in this two-treatment parallel-design study to have 84 percent power to detect a change in urine output by 75 mL/hr at a two-sided 0.05 significance level (using standard deviation of 35 mL/hr for urine output). Thus 10 patient were included in each device arm of the study.Chi-square analysis was used to compare discrete variables.

A two tailed Student's t-test was used to compare continuous variables. A repeated measures analysis of variance (ANOVA) was used to compare changes in clinical variables laboratory measurements across time points. A P value \< 0.05 was considered significant. For individual comparisons post-hoc testing was performed with a paired t-test analysis with Bonferroni correction for 2 comparisons and thus only a P value \< 0.025 will considered significant for the repeated measures analyses. A Student 2-tailed paired t test will be used to compare placebo and active drug values for each individual time point.

Conditions

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Congestive Heart Failure Cardiorenal Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Total Artificial Heart

Nesiritide

Group Type EXPERIMENTAL

nesiritide

Intervention Type DRUG

nesiritide at 0.005 mcg/kg/min without a bolus starting 6 hours after the subject has come off of cardiopulmonary bypass and will continue for 48 hours.

Total Artificial Heart: Placebo

Control arm for subjects receiving the Total Artificial Heart and randomized to receive placebo

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

placebo bolus starting 6 hours after the subject has come off of cardiopulmonary bypass and will continue for 48 hours.

LVAD: Nesiritide

Active arm of the LVAD group

Group Type ACTIVE_COMPARATOR

nesiritide

Intervention Type DRUG

nesiritide at 0.005 mcg/kg/min without a bolus starting 6 hours after the subject has come off of cardiopulmonary bypass and will continue for 48 hours.

LVAD: Placebo

Control arm for subjects receiving LVAD and randomized to placebo

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

placebo bolus starting 6 hours after the subject has come off of cardiopulmonary bypass and will continue for 48 hours.

Interventions

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nesiritide

nesiritide at 0.005 mcg/kg/min without a bolus starting 6 hours after the subject has come off of cardiopulmonary bypass and will continue for 48 hours.

Intervention Type DRUG

placebo

placebo bolus starting 6 hours after the subject has come off of cardiopulmonary bypass and will continue for 48 hours.

Intervention Type DRUG

Other Intervention Names

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Natrecor

Eligibility Criteria

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Inclusion Criteria

* Implanted with a total artificial heart (CardioWest) or Left ventricular assist device (HeartMate II)
* Age \> 18 years

Exclusion Criteria

* Previous calcineurin inhibitor (CNI) exposure
* Hemodialysis prior to device implant
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Virginia Commonwealth University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Keyur B. Shah, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University Medical Center

Locations

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Virginia Commonwealth University Medical Center

Richmond, Virginia, United States

Site Status

Countries

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United States

Other Identifiers

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HM15024

Identifier Type: -

Identifier Source: org_study_id

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