Use of Nesiritide (BNP) in Kidney Function in Patients With Congestive Heart Failure (CHF) and Kidney Failure

Efficacy of Intra-renal Infusion of BNP in Enhancing Renal Function in Human CHF With Cardiorenal Syndrome: A Pilot Study

The objective of this study is to determine the safety and effectiveness of intrarenal administration of brain natriuretic peptide (BNP) in improving renal function as measured by glomerular filtration rate (GFR) and sodium excretion in patients hospitalized with acute congestive heart failure (CHF) and deterioration of kidney function (cardiorenal syndrome).

Study Overview

• Status: Terminated
• Conditions: Cardiorenal Syndrome
• Intervention / Treatment: Drug: Nesiritide

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Age 18 years and older
• Clinical diagnosis of class III-IV CHF requiring hospitalization
• Current acute CHF decompensation
• Systolic BP > 90 mmHg
• Stable cardiac rhythm
• Estimated creatinine clearance by the Cockcroft-Gault equation of less than or equal to 60 mL/min.
• Worsening renal function after greater than or equal to 24 hours of standard therapy as defined by a plasma creatinine concentration greater than their admission of 0.3 mg/dL and a 10% increase from hospital admission creatinine OR creatinine which remains at 0.3 mg/dL and 10% increase from baseline draw done within 4 weeks of hospitalization
• Ability to provide informed consent

Exclusion Criteria

• Patients needing emergency coronary revascularization or those who may have rapidly changing cardiac function (i.e., patients with acute myocardial infarction or shock)
• Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period
• Systolic blood pressure < 90 mmHg or cardiogenic shock
• Requirement of pressors for maintenance of blood pressure
• Intra-aortic blood pump use
• History of significant uncorrected renal artery stenosis as defined by >50% stenosis
• Severe aortic or mitral stenosis or significant LV outflow tract obstruction
• Pregnant or nursing women
• Prisoners
• Contraindication to nesiritide
• Contraindication to heparin
• Cause of acute renal dysfunction can be reasonably ascribed to factors other than heart failure or its treatment
• Inability to have NSAID dose held for up to 30 hours, if being treated with these medications
• Ongoing treatment with calcineurin inhibitors (cyclosporine or tacrolimus)
• Administration of radiocontrast medium within 7 days of enrollment or anticipated use of such agents during the study (other than the minimal contrast required to place the renal infusion catheter)
• Known bleeding diathesis
• Known condition that would increase the likelihood of vascular perforation or trauma, dissection such as Marfan's syndrome, cystic medial necrosis, abdominal or thoracoabdominal aortic dissection, mycotic aneurysm, abdominal aneurysm, thoracoabdominal aneurysm, renal artery aneurysm, thoracic aneurysm involving the visceral region of the aorta, and severe calcification in the area of the renal arteries
• Solitary kidney or solitary functioning kidney
• Iodine allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nesiritide; Subjects received an intrarenal infusion of nesiritide at 0.005 microgram/kg/min for 6 hours, 0.01 microgram/kg/min for 6 hours, 0.02 microgram/kg/min for 6 hours, and 0.03 microgram/kg/min for 6 hours.	Drug: Nesiritide; Nesiritide 0.005 ug/kg/min IV for 6 hours, then to 0.01 ug/kg/min for 6 hours then to 0.02ug/kg/min for 6 hours then to 0.03 ug/kg/min for the last 6 hours.; Other Names: Natrecor; brain natriuretic peptide (BNP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glomerular Filtration Rate (GFR) at 24 Hours	Kidney function was to be measured by GFR determined by iothalamate clearance. GFR describes the flow rate of filtered fluid through the kidney measured in milliliters per minute per 1.73 m^2 of body surface area. A lower GFR means the kidney is not filtering normally. An estimated GFR of less than 60 mg/min/1.73 m^2 of body surface area is considered to be impaired kidney function.	baseline, 24 hours after start of infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Urinary Sodium Excretion at 24 Hours	The fractional excretion of sodium (FENa) measures the percent of filtered sodium that is excreted in the urine. This calculation is widely used to help differentiate prerenal disease (decreased renal perfusion) from acute tubular necrosis (ATN) as the cause of acute kidney injury (AKI, formerly called acute renal failure).	baseline, 24 hours after start of infusion

Collaborators and Investigators

• Sponsor: Horng Chen
• Collaborators: FlowMedica, Inc.

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: June 30, 2006
• First Submitted That Met QC Criteria: July 3, 2006
• First Posted (Estimate): July 4, 2006

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: October 3, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Disease; Renal Insufficiency; Heart Failure; Syndrome; Cardio-Renal Syndrome; Physiological Effects of Drugs; Natriuretic Agents; Natriuretic Peptide, Brain
• Other Study ID Numbers: 05-004007