Low Dose Intravenous (IV) Infusion of BNP in the Presence and Absence of Acute Type V Phosphodiesterase (PDE V) in Improving Renal Function in Hospitalized Chronic Heart Failure (CHF) Patients With Renal Dysfunction

NCT00972569 | Completed Phase 1 DMC

• 2 other identifiers: 09-0033031R01HL08415501A2
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is to determine if low doses of BNP can improve renal function in people with chronic heart failure with renal dysfunction, also to determine whether Sildenafil assists with improvement. This study will enroll only hospitalized patients with heart failure.

Conditions

Heart Failure; Renal Dysfunction

Keywords

BNP with or without PDE-V in heart failure

Outcome Measures

Primary Outcomes (1)

• The primary endpoint for this aim will be a comparison of the 3 groups for the percent change in creatinine clearance, and blood urea nitrogen from baseline to 48 hours.

  each blood and urine collections 4 time points

Secondary Outcomes (1)

• The secondary endpoints for this aim will be a comparison of the 3 groups for the percent change in plasma, sodium excretion, aldosterone, and renal cGMP generation from baseline line to 48 hours

  each blood and urine collection at 4 time points

Study Arms (3)

BNP with PDE-V

ACTIVE COMPARATOR

BNP (Nesiritide) will be infused starting at 0.0025 g/Kg/min IV for 3 hours, if tolerated increased to 0.005 g/kg/min for 45 hours without bolus with PDEV inhibition, they will also receive Sildenafil 12.5 mg at timepoints 0,12, 24 and 36 hours

Drug: BNP and PDE-V

BNP (Nesiritide) will be infused at 0.005 u/Kg/min IV for 48 h

ACTIVE COMPARATOR

BNP (Nesiritide) will be infused at 0.025 ug/Kg/min IV for 3 hours then 0.005ug/kg/min 45 hours without bolus. No PDE-V is given.

Drug: BNP

standard care

NO INTERVENTION

Patients randomized to this group will continue to receive therapy at the discretion of the heart failure specialist who is managing the patient (with the exception of BNP and low dose dopamine). Blood and Urine will be collected after the patient has been randomized for 48 hours

Interventions

BNP and PDE-V DRUG

low dose BNP 0.025 u/kg/min for 3 hours then 0.005ug/kg/min 45 hours PDE-V 12.5 mg 4 time points

Also known as: nesiritide (Natrecor), Viagra

BNP with PDE-V

BNP DRUG

low dose BNP at 0.025 u/kg/min if tolerated then at 0.005 ug/kg/min for 45 hours

Also known as: Nesiritide (Natrecor)

BNP (Nesiritide) will be infused at 0.005 u/Kg/min IV for 48 h

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients admitted to St Mary's Hospital, Mayo Clinic Rochester MN with NYHA class III-IV decompensated CHF with renal dysfunction as Calculated creatinine clearance of equal or less than 60 ml/min but greater than 20 ml/min using the Cockcroft-Gault formula.

You may not qualify if:

• Cause of acute renal dysfunction can be reasonably ascribed to factors other than heart failure or its treatment
• Known intrinsic renal diseases or renal artery stenosis of =\>50%
• Patients taking Nitrates within the previous 24 hours
• 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. Hgb \< 10 mg/dL
• Pregnant or nursing women.
• Contraindication to nesiritide.
• Inability to have NSAID dose held for up to 30 hours, if being treated with these medications.
• Administration of radiocontrast medium within 7 days of enrollment or anticipated use of such agents during the study

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institutes of Health (NIH): collaborator

Related Publications (1)

• Hubers SA, Benike SL, Johnson BK, McKie PM, Scott C, Chen HH. Renal Effects of Combination Phosphodiesterase V Inhibition and Low-Dose B-Type Natriuretic Peptide in Acute Heart Failure: A Randomized Clinical Trial. Circ Heart Fail. 2024 Dec;17(12):e011761. doi: 10.1161/CIRCHEARTFAILURE.124.011761. Epub 2024 Nov 8.

  PMID: 39513267 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Heart Failure; Renal Insufficiency

Interventions

Natriuretic Peptide, Brain; Sildenafil Citrate

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Natriuretic Peptides; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Dr Horng H Chen, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 3, 2009
• First Posted: September 7, 2009
• Study Start: October 1, 2009
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01