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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01663662
• Other study ID #: 11-PAF06621
• Status: Withdrawn
• Phase: Phase 4
• First received: August 8, 2012
• Last updated: December 10, 2015
• Start date: August 2012
• Est. completion date: November 2013

Study information

• Verified date: December 2015
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 99 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Heart Failure
• Renal Insufficiency

Intervention

Drug:
• Tolvaptan

• placebo

Locations

Country	Name	City	State
United States	University of Michigan Health Systems	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	Otsuka Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Treatment Failure	Need to increase diuretic dose in tolvaptan study group prior to 72 hr time point	72hr	No
Primary	Renal dysfunction	Increase in serum creatinine > 0.3 mg/dL within a 96 hours from enrollment	96 hours	No
Secondary	Weight	Change in weight over 24, 48, 72, and 96 hours	24, 78, 72, 96	No
Secondary	Urine output	Net urine output over 24, 48, 72, and 96 hours	24, 48, 72, 96	No
Secondary	Hospitalization length of stay		10	No