Does Nesiritide Provide Renal Protection

Phase 2

Completed

• Conditions: Renal Failure
• Interventions: Drug: Placebo; Drug: Nesiritide

• Registration Number: NCT01440881
• Lead Sponsor: University of Florida

Brief Summary

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

Detailed Description

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).

Study Timeline

• Study Start: 2010-04
• Study First Submitted: 2011-02-10
• Study First Submitted QC: 2011-09-26
• Study First Posted: 2011-09-27
• Primary Completion: 2012-12
• Study Completion: 2012-12
• Results First Submitted: 2014-01-22
• Results First Submitted QC: 2014-01-22
• Results First Posted: 2014-03-06
• Status Verified: 2014-05
• Last Update Submitted: 2014-05-16
• Last Update Posted: 2014-06-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	infuses at 0.01MCG/KG/min for 48 hours
Nesiritide	Nesiritide	infuses at 0.01 MCG (micrograms)/KG (kilograms)/min (minute) for 48 hours

Primary Outcome Measures

Name	Time	Method
Measure Neutrophils to Measure Kidney Injury	30 days from the start of infusion	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.
The Examine and Measure Cytokines to Measure Kidney Injury	30 days from the start of infusion	Serial measurement of serum cytokine profiles were measured with multiplex Luminex plates that enable the simultaneous measurement of 23 cytokines.
The Examine and Measure Endothelin-1 to Measure Kidney Injury	30 days from the start of infusion	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.
The Examine and Measure Urinary NGAL to Measure Kidney Injury	A change in urinary NGAL 2 hours after bypass was stopped and 5 minutes after the start of spontaneous circulation was resumed.	Urinary NGAL,a biomarker for kidney injury was measured.

Trial Locations

Locations (1)

University of Florida; 🇺🇸 Gainesville, Florida, United States