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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01663662
Recruitment Status : Withdrawn (Lack of eligible patients)
First Posted : August 13, 2012
Last Update Posted : December 11, 2015
Otsuka Pharmaceuticals
Information provided by (Responsible Party):
Barry E. Bleske, University of Michigan

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.

Condition or disease Intervention/treatment Phase
Heart Failure Drug: Tolvaptan Drug: placebo Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : August 2012
Actual Primary Completion Date : November 2013
Actual Study Completion Date : November 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure
Drug Information available for: Tolvaptan
U.S. FDA Resources

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Renal dysfunction [ Time Frame: 96 hours ]
    Increase in serum creatinine > 0.3 mg/dL within a 96 hours from enrollment

Secondary Outcome Measures :
  1. Weight [ Time Frame: 24, 78, 72, 96 ]
    Change in weight over 24, 48, 72, and 96 hours

  2. Urine output [ Time Frame: 24, 48, 72, 96 ]
    Net urine output over 24, 48, 72, and 96 hours

  3. Hospitalization length of stay [ Time Frame: 10 ]

Other Outcome Measures:
  1. Treatment Failure [ Time Frame: 72hr ]
    Need to increase diuretic dose in tolvaptan study group prior to 72 hr time point

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01663662

United States, Michigan
University of Michigan Health Systems
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
Otsuka Pharmaceuticals
Principal Investigator: Barry E Bleske, Pharm. D. University of Michigan

Responsible Party: Barry E. Bleske, Associate Professor, University of Michigan Identifier: NCT01663662     History of Changes
Other Study ID Numbers: 11-PAF06621
First Posted: August 13, 2012    Key Record Dates
Last Update Posted: December 11, 2015
Last Verified: December 2015

Additional relevant MeSH terms:
Heart Failure
Renal Insufficiency
Heart Diseases
Cardiovascular Diseases
Kidney Diseases
Urologic Diseases
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Physiological Effects of Drugs