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

Study Overview
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Brief Summary
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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.

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

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Tolvaptan
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tolvaptan Arm<br>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 | Drug: Tolvaptan<br> <br> |
| Placebo Comparator: Placebo<br>Placebo x 3 days and standard of care continuous infusion diuretic | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal dysfunction | Increase in serum creatinine > 0.3 mg/dL within a 96 hours from enrollment | 96 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight | Change in weight over 24, 48, 72, and 96 hours | 24, 78, 72, 96 | 
| Urine output | Net urine output over 24, 48, 72, and 96 hours | 24, 48, 72, 96 | 
| Hospitalization length of stay |  | 10 |