Clinical trial NCT01663662: 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
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Heart Failure
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Otsuka Pharmaceuticals
First posted: 2012-08-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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.

Primary outcomes:
measure: Renal dysfunction
timeFrame: 96 hours
Secondary outcomes:
measure: Weight
timeFrame: 24, 78, 72, 96
measure: Urine output
timeFrame: 24, 48, 72, 96
measure: Hospitalization length of stay
timeFrame: 10
Other outcomes:
measure: Treatment Failure
timeFrame: 72hr
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Health Systems
state: Michigan
Study officials:
affiliation: University of Michigan
name: Barry E Bleske, Pharm. D.
role: PRINCIPAL_INVESTIGATOR
References: