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

This study has been withdrawn prior to enrollment.
(Lack of eligible patients)
Sponsor:
Collaborator:
Otsuka Pharmaceuticals
Information provided by (Responsible Party):
Barry E. Bleske, University of Michigan
ClinicalTrials.gov Identifier:
NCT01663662
First received: August 8, 2012
Last updated: December 9, 2013
Last verified: August 2012
  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

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • 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


Enrollment: 0
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
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01663662

Locations
United States, Michigan
University of Michigan Health Systems
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
Otsuka Pharmaceuticals
Investigators
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: December 9, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases

ClinicalTrials.gov processed this record on November 25, 2014