Does Nesiritide Provide Renal Protection

Does Nesiritide Provide Renal Protection By Attenuating the Inflammatory Response

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

Study Overview

• Status: Completed
• Conditions: Renal Failure
• Intervention / Treatment: Drug: Nesiritide; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Thomas Beaver, MD, University of Florida

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: February 10, 2011
• First Submitted That Met QC Criteria: September 26, 2011
• First Posted (Estimate): September 27, 2011

Study Record Updates

• Last Update Posted (Estimate): June 6, 2014
• Last Update Submitted That Met QC Criteria: May 16, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: cardiopulmonary bypass; renal failure
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Physiological Effects of Drugs; Natriuretic Agents; Natriuretic Peptide, Brain
• Other Study ID Numbers: 70-2010; 09KW-03 (Other Grant/Funding Number: Florida Department of Health)