Does Nesiritide Provide Renal Protection

• ClinicalTrials.gov Identifier: NCT01440881
• Recruitment Status: Completed
• First Posted: September 27, 2011
• Results First Posted: March 6, 2014
• Last Update Posted: June 6, 2014
• Sponsor: University of Florida
• Information provided by (Responsible Party): University of Florida

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Renal Failure	Drug: Nesiritide; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Does Nesiritide Provide Renal Protection By Attenuating the Inflammatory Response
• Study Start Date: April 2010
• Actual Primary Completion Date: December 2012
• Actual Study Completion Date: December 2012

Arms and Interventions

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 Name: 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 Name: kidney protection post cardiopulmonary bypass

Outcome Measures

Primary Outcome Measures :

1. Measure Neutrophils to Measure Kidney Injury [ Time Frame: 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.
2. The Examine and Measure Cytokines to Measure Kidney Injury [ Time Frame: 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.
3. The Examine and Measure Endothelin-1 to Measure Kidney Injury [ Time Frame: 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.
4. The Examine and Measure Urinary NGAL to Measure Kidney Injury [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

Sponsors and Collaborators

University of Florida

Investigators

• Principal Investigator: Thomas Beaver, MD; University of Florida

More Information

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT01440881
• Other Study ID Numbers: 70-2010; 09KW-03 ( Other Grant/Funding Number: Florida Department of Health )
• First Posted: September 27, 2011
• Results First Posted: March 6, 2014
• Last Update Posted: June 6, 2014
• Last Verified: May 2014

Keywords provided by University of Florida:

renal failure; cardiopulmonary bypass

Additional relevant MeSH terms:

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Natriuretic Peptide, Brain; Natriuretic Agents; Physiological Effects of Drugs