Tolvaptan for Advanced or Refractory Heart Failure

University of Calgary

Status and phase: Terminated; Phase 4

Conditions: Hyponatremia; Heart Failure

Treatments: Drug: Tolvaptan; Drug: Standard of care diuretic therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT02959411

REB16-0064

Details and patient eligibility

About

This study will clarify the clinical usefulness of Tolvaptan therapy in patients with complicated acute decompensated heart failure and hyponatremia (low blood sodium).

Full description

Despite its demonstrated efficacy and tolerability, Tolvaptan remains underutilized for the treatment of acute decompensated heart failure (ADHF) in many centers. Post-hoc analysis suggests that Tolvaptan may provide optimal outcomes in patients with more advanced heart failure (HF) including those with cardiorenal syndrome, marked hyponatremia and severe congestion, or a combination of those conditions. The efficacy of Tolvaptan in HF patients with loop diuretic resistance and in those requiring inotropic support remains uncertain.

The purpose of this study is to examine the benefit of Tolvaptan versus the current standard of care diuretic therapy for patients hospitalized with ADHF and evidence of advanced or complex HF with severe hyponatremia. Patients with advanced or complex disease are defined as those with suboptimal diuretic response over a 48 hour period.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Hospital admission for ADHF with volume overload as evidenced by ≥ 2 of the following: Elevated JVP, peripheral edema, ascites, pulmonary rales, congestion on chest X-ray, elevated NT-pro-BNP > 2000 pg/ml
• Inadequate clinical response indicated by body weight loss < 1.0 kg/day over 48 hours despite adequate doses of IV loop diuretic (at least 40 mg furosemide daily) and fluid restriction 2 L/24 hours.
• ≥1 of the following over the preceding 48 hours: Potential need for inotropic support to improve urine output, and/or renal insufficiency (estimated glomerular filtration rate <45 mL/min/1.73 m2)
• Serum sodium ≤134 mmol/L
• ≥18 years-old

Exclusion criteria

• Cardiac surgery within 60 days of enrollment
• Planned cardiac mechanical support or transplant; subjects with previously implanted ventricular assist device (VAD) will not be excluded
• Need for intravenous pressor support for symptomatic hypotension
• Biventricular pacemaker placement within the last 60 days
• Hemofiltration or dialysis
• Known cirrhosis
• Supine systolic arterial blood pressure less than 85 mmHg
• Refusal or inability to sign informed consent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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9 participants in 2 patient groups

Tolvaptan

Experimental group

Description:

Tolvaptan 15-60 mg, once daily for 4 days or until hospital discharge

Treatment:

Drug: Tolvaptan

Standard of care diuretic therapy

Active Comparator group

Description:

Usual standard of care diuretic therapy for patients with acute decompensated heart failure

Treatment:

Drug: Standard of care diuretic therapy