The Use of Tolvaptan to Prevent Renal Dysfunction in High Risk Patients With Heart Failure-Pilot Study

NCT ID: NCT01663662

Last Updated: 2015-12-11

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2013-11-30

Brief Summary

It is well known that the use of loop diuretics in acute setting may decrease glomerular filtration rate (GFR) and increase serum creatinine leading to renal dysfunction. Loop diuretic induced elevation in serum creatinine can lead to increase in length of hospital stay and possibly morbidity. Previous studies have suggested that tolvaptan unlike aggressive loop diuretic therapy may not activate neurohormonal system nor decrease renal blood flow. These properties may make tolvaptan a useful addition to diuretic therapy to prevent renal dysfunction in high-risk patients. Therefore the primary objective of this study is to determine if the use of tolvaptan in combination with diuretic therapy may prevent development of renal dysfunction in high risk patients with heart failure.

Hypothesis: Administration of tolvaptan in combination with continuous loop diuretic therapy in acutely decompensated heart failure patients at high risk for developing diuretic induced renal dysfunction will have a lower proportion of patients increasing their serum creatinine > 0.3 mg/dL within a 96 hour time frame as compared to patients just receiving standard of care continuous infusion diuretic.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Tolvaptan Arm

Tolvaptan 30 mg qd x 3 days and Low Dose Loop Continuous Infusion - Initial Dosing:

Furosemide - 10 mg/hr Bumentanide - 0.25 mg/hr Torsemide - 5 mg/hr

Group Type: ACTIVE_COMPARATOR

Tolvaptan

Intervention Type: DRUG

Placebo

Placebo x 3 days and standard of care continuous infusion diuretic

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Interventions

Tolvaptan

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• ≥ 18 years old
• Prior clinical diagnosis of systolic heart failure (EF < 40% within the past 18 months) with daily home use of oral loop diuretic for at least one month.
• Daily oral dose of furosemide ≥ 40 mg and ≤ 240 mg (or equivalent)
• Identified within 24 hours of hospital admission
• Heart failure defined by at least 1 symptom (dyspnea, orthopnea, or edema) AND 1 sign (rales on auscultation, peripheral edema, ascites, pulmonary vascular congestion on chest radiography)
• Anticipated need for IV loop diuretics for at least 48 hours
• Likely requires daily net urine output in the range of 1-3 L/day for over a 72-96 hour time period.
• Albumin level < 3.5 g/dL
• Willingness to provide informed consent

Exclusion Criteria

• Received or planned IV vasoactive treatment (inotropes, vasodilators) or ultra-filtration therapy for heart failure
• BNP < 250 ng/ml or NT-proBNP < 1000 mg/ml (if drawn for clinical purposes)
• Systolic BP < 90 mmHg
• Serum creatinine > 3.0 mg/dl at baseline or renal replacement therapy or creatinine clearances < 10 mL/min
• Serum sodium > 145 mEq/L
• Acute coronary syndrome within 4 weeks
• Anticipated need for coronary angiography or other procedures requiring IV contrast.
• Patients receiving any of the following drugs: clarithromycin, ketoconazole, itraconazole,ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, telithromycin, erythromycin, fluconazole, aprepitant, diltiazem, verapamil, cyclosporine, and grapefruit juice.
• Pregnant or nursing patients.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka Pharmaceuticals

UNKNOWN

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Barry E. Bleske

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Barry E Bleske, Pharm. D.

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan Health Systems

Ann Arbor, Michigan, United States

Countries

United States

Other Identifiers

11-PAF06621

Identifier Type: -

Identifier Source: org_study_id