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

Primary Purpose

Heart Failure

Status

Withdrawn

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Tolvaptan

placebo

About this trial

This is an interventional prevention trial for Heart Failure

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Michigan Health Systems

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Tolvaptan Arm

Placebo

Arm Description

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

Placebo x 3 days and standard of care continuous infusion diuretic

Outcomes

Primary Outcome Measures

Renal dysfunction

Increase in serum creatinine > 0.3 mg/dL within a 96 hours from enrollment

Secondary Outcome Measures

Weight

Change in weight over 24, 48, 72, and 96 hours

Urine output

Net urine output over 24, 48, 72, and 96 hours

Hospitalization length of stay

Full Information

NCT ID

NCT01663662

First Posted

August 8, 2012

Last Updated

December 10, 2015

Sponsor

University of Michigan

Collaborators

Otsuka Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01663662

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Withdrawn

Why Stopped

Lack of eligible patients

Study Start Date

August 2012 (undefined)

Primary Completion Date

November 2013 (Actual)

Study Completion Date

November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Michigan

Collaborators

Otsuka Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heart Failure

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tolvaptan Arm

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo x 3 days and standard of care continuous infusion diuretic

Intervention Type

Drug

Intervention Name(s)

Tolvaptan

Intervention Type

Drug

Intervention Name(s)

placebo

Primary Outcome Measure Information:

Title

Renal dysfunction

Description

Increase in serum creatinine > 0.3 mg/dL within a 96 hours from enrollment

Time Frame

96 hours

Secondary Outcome Measure Information:

Title

Weight

Description

Change in weight over 24, 48, 72, and 96 hours

Time Frame

24, 78, 72, 96

Title

Urine output

Description

Net urine output over 24, 48, 72, and 96 hours

Time Frame

24, 48, 72, 96

Title

Hospitalization length of stay

Time Frame

Other Pre-specified Outcome Measures:

Title

Treatment Failure

Description

Need to increase diuretic dose in tolvaptan study group prior to 72 hr time point

Time Frame

72hr

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Barry E Bleske, Pharm. D.

Organizational Affiliation

University of Michigan

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Michigan Health Systems

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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