The Use of Tolvaptan to Prevent Renal Dysfunction in High Risk Patients With Heart Failure-Pilot Study
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Heart Failure |
Drug: Tolvaptan Drug: placebo |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention |
| Official Title: | The Use of Tolvaptan to Prevent Renal Dysfunction in High Risk Patients With Acute Decompensated Heart Failure-Pilot Study |
- Renal dysfunction [ Time Frame: 96 hours ] [ Designated as safety issue: No ]Increase in serum creatinine > 0.3 mg/dL within a 96 hours from enrollment
- Weight [ Time Frame: 24, 78, 72, 96 ] [ Designated as safety issue: No ]Change in weight over 24, 48, 72, and 96 hours
- Urine output [ Time Frame: 24, 48, 72, 96 ] [ Designated as safety issue: No ]Net urine output over 24, 48, 72, and 96 hours
- Hospitalization length of stay [ Designated as safety issue: No ]
- Treatment Failure [ Time Frame: 72hr ] [ Designated as safety issue: No ]Need to increase diuretic dose in tolvaptan study group prior to 72 hr time point
| Estimated Enrollment: | 40 |
| Study Start Date: | August 2012 |
| Estimated Primary Completion Date: | December 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 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 |
Drug: Tolvaptan |
|
Placebo Comparator: Placebo
Placebo x 3 days and standard of care continuous infusion diuretic
|
Drug: placebo |
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| United States, Michigan | |
| University of Michigan Health Systems | Recruiting |
| Ann Arbor, Michigan, United States, 48109 | |
| Contact: Barry E Bleske, Pharm. D. 734-764-5341 bbleske@umich.edu | |
| Principal Investigator: Barry E. Bleske, Pharm. D. | |
| Sub-Investigator: Michael Dorsch, Pharm. D. | |
| Sub-Investigator: Keith Aaronson, M.D. | |
| Sub-Investigator: Audrey Wu, M.D. | |
| Sub-Investigator: Neha Shah | |
| Principal Investigator: | Barry E Bleske, Pharm. D. | University of Michigan |
More Information
No publications provided
| Responsible Party: | Barry E. Bleske, Associate Professor, University of Michigan |
| ClinicalTrials.gov Identifier: | NCT01663662 History of Changes |
| Other Study ID Numbers: | 11-PAF06621 |
| Study First Received: | August 8, 2012 |
| Last Updated: | August 10, 2012 |
| Health Authority: | United States: Institutional Review Board |
Additional relevant MeSH terms:
|
Heart Failure Heart Diseases Cardiovascular Diseases |
ClinicalTrials.gov processed this record on May 23, 2013