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

NCT01663662 | Withdrawn Phase 4

• 1 other identifier: 11-PAF06621
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Renal dysfunction

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

  96 hours

Secondary Outcomes (3)

• Weight

  24, 78, 72, 96

• Urine output

  24, 48, 72, 96

• Hospitalization length of stay

  10

Other Outcomes (1)

• Treatment Failure

  72hr

Study Arms (2)

Tolvaptan Arm

ACTIVE COMPARATOR

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

PLACEBO COMPARATOR

Placebo x 3 days and standard of care continuous infusion diuretic

Drug: placebo

Interventions

Tolvaptan DRUG

Tolvaptan Arm

placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan: lead
• Otsuka Pharmaceuticals: collaborator

Study Sites (1)

University of Michigan Health Systems

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Barry E Bleske, Pharm. D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 8, 2012
• First Posted: August 13, 2012
• Study Start: August 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: December 11, 2015

Record last verified: 2015-12

Locations

US (1)