Does Nesiritide Provide Renal Protection

Study Overview
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Brief Summary
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This project evaluates whether nesiritide, human recombinant brain natriuretic peptide, confers renal protection during cardiovascular surgery by attenuating the inflammatory response.

Detailed Description
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This will be a randomized, prospective blinded pilot study comparing nesiritide to placebo in patients undergoing aortic arch, ascending aorta, aortic valve or mitral valve surgery with baseline GFR 30-90ml/min. Patients were randomized to either placebo or nesiritide (administered prophylactically starting in the operating room prior to incision at 0.01 mcg/kg /minute with no bolus and continued for 48 hours).

Official Title
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Does Nesiritide Provide Renal Protection By Attenuating the Inflammatory Response

Conditions
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Renal Failure

Intervention / Treatment
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* Drug: Nesiritide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing surgery on their aortic arch, ascending aorta, or having aortic valve or mitral valve surgery Baseline MDRD (modification of diet in renal disease) calculated GFR (Glomerular Filtration Rate) 30-90 ml/min. Signed Informed Consent Exclusion Criteria: Age <18 or >80 Ejection Fraction <30%. Presence of endocarditis or other infection. Presence or anticipated use of an intra-aortic balloon pump. History of an organ transplant. History of an adverse reaction to nesiritide. Surgery performed without cardiopulmonary bypass. Receiving Aprotinin Dopamine administered in doses <5 mcg /kg min. Women of child bearing potential or pregnant or breastfeeding. Participation in any other investigational trial Jehovah Witness Bleeding Disorder Active Endocarditis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nesiritide<br>infuses at 0.01 MCG (micrograms)/KG (kilograms)/min (minute) for 48 hours | Drug: Nesiritide<br>* infuses at 0.01MCG/KG/min for 48 hours<br>* Other names: kidney protection post cardiopulmonary bypass.;|
| Placebo Comparator: Placebo<br>infuses at 0.01MCG/KG/min for 48 hours | Drug: Placebo<br>* infuses at 0.01MCG/KG/min for 48 hours<br>* Other names: kidney protection post cardiopulmonary bypass;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure Neutrophils to Measure Kidney Injury | 0.35 mL of whole blood from each patient was applied to a microfluidics chip to isolate neutrophils. Total RNA was subsequently isolated and gene expression (for all genes listed below) was measured with an Affymetrix gene chip. Data was normalized using RMA (Robust multi-array average) and expressed as log2 expression. | 30 days from the start of infusion | 
| The Examine and Measure Cytokines to Measure Kidney Injury | Serial measurement of serum cytokine profiles were measured with multiplex Luminex plates that enable the simultaneous measurement of 23 cytokines. | 30 days from the start of infusion | 
| The Examine and Measure Endothelin-1 to Measure Kidney Injury | Serial measurements of Endothelin-1 levels were measured to determine if natriuretic peptides exert their renal protective effects by preserving renal afferent arteriole flow by antagonizing the vasoconstrictive effects of Endothelin-1. | 30 days from the start of infusion | 
| The Examine and Measure Urinary NGAL to Measure Kidney Injury | Urinary NGAL,a biomarker for kidney injury was measured. | A change in urinary NGAL 2 hours after bypass was stopped and 5 minutes after the start of spontaneous circulation was resumed. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal failure, cardiopulmonary bypass