- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01836809
Nesiritide and Renal Function After the Total Artificial Heart
The Impact of Nesiritide on Renal Function After Implantation of the Total Artificial Heart and Left Ventricular Assist Devices
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Virginia
-
Richmond, Virginia, United States, 23298
- Virginia Commonwealth University Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Total Artificial Heart
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 Names:
|
Placebo Comparator: Total Artificial Heart: Placebo
Control arm for subjects receiving the Total Artificial Heart and randomized to receive 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
|
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 Names:
|
Placebo Comparator: LVAD: Placebo
Control arm for subjects receiving LVAD and randomized to placebo
|
placebo bolus starting 6 hours after the subject has come off of cardiopulmonary bypass and will continue for 48 hours.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Glomerular Filtration Rate
Time Frame: 46 hours
|
46 hours
|
Renal Plasma Flow
Time Frame: 46 Hours
|
46 Hours
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Need for Hemodialysis/Renal Replacement Therapy
Time Frame: 90 days
|
90 days
|
Urine Output
Time Frame: 46 Hours
|
46 Hours
|
Time to Renal Failure
Time Frame: 46 Hours
|
46 Hours
|
Total Diuretic Requirement
Time Frame: 46 Hours
|
46 Hours
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Keyur B. Shah, MD, Virginia Commonwealth University Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- HM15024
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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