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Nesiritide and Renal Function After the Total Artificial Heart

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ClinicalTrials.gov Identifier: NCT01836809
Recruitment Status : Terminated (Futility for enrollment)
First Posted : April 22, 2013
Results First Posted : August 18, 2014
Last Update Posted : February 8, 2016
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Congestive Heart Failure Cardiorenal Syndrome Drug: nesiritide Drug: placebo Phase 4

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: The Impact of Nesiritide on Renal Function After Implantation of the Total Artificial Heart and Left Ventricular Assist Devices
Study Start Date : April 2013
Actual Primary Completion Date : May 2014
Actual Study Completion Date : May 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Tests
Drug Information available for: Nesiritide

Arm Intervention/treatment
Experimental: Total Artificial Heart
Nesiritide
Drug: 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.
Other Name: Natrecor

Placebo Comparator: Total Artificial Heart: Placebo
Control arm for subjects receiving the Total Artificial Heart and randomized to receive placebo
Drug: placebo
placebo bolus starting 6 hours after the subject has come off of cardiopulmonary bypass and will continue for 48 hours.

Active Comparator: LVAD: Nesiritide
Active arm of the LVAD group
Drug: 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.
Other Name: Natrecor

Placebo Comparator: LVAD: Placebo
Control arm for subjects receiving LVAD and randomized to placebo
Drug: placebo
placebo bolus starting 6 hours after the subject has come off of cardiopulmonary bypass and will continue for 48 hours.




Primary Outcome Measures :
  1. Glomerular Filtration Rate [ Time Frame: 46 hours ]
  2. Renal Plasma Flow [ Time Frame: 46 Hours ]

Secondary Outcome Measures :
  1. Need for Hemodialysis/Renal Replacement Therapy [ Time Frame: 90 days ]
  2. Urine Output [ Time Frame: 46 Hours ]
  3. Time to Renal Failure [ Time Frame: 46 Hours ]
  4. Total Diuretic Requirement [ Time Frame: 46 Hours ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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 ClinicalTrials.gov identifier (NCT number): NCT01836809


Locations
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United States, Virginia
Virginia Commonwealth University Medical Center
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
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Principal Investigator: Keyur B. Shah, MD Virginia Commonwealth University Medical Center

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Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT01836809    
Other Study ID Numbers: HM15024
First Posted: April 22, 2013    Key Record Dates
Results First Posted: August 18, 2014
Last Update Posted: February 8, 2016
Last Verified: January 2016
Keywords provided by Virginia Commonwealth University:
Total Artificial Heart
Left Ventricular Assist Device
Natriuretic peptides
Heart Failure
Cardiorenal Syndrome
Additional relevant MeSH terms:
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Cardio-Renal Syndrome
Heart Failure
Heart Diseases
Cardiovascular Diseases
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Natriuretic Peptide, Brain
Natriuretic Agents
Physiological Effects of Drugs