Tolvaptan for Advanced or Refractory Heart Failure

Phase 4TerminatedNCT02959411

University of Calgary9 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Heart Failure Hyponatremia

Interventions

TolvaptanDRUG

Tolvaptan is a selective vasopressin receptor antagonist that inhibits activation of the V2 receptor and synthesis and insertion of the aquaporin2 channel into the apical membrane of the renal collecting duct. Tolvaptan inhibits the reabsorption of free water, inducing free water diuresis and increasing serum sodium levels without adversely influencing electrolyte levels or stimulating the sympathetic nervous system or renin-angiotensin system.

Standard of care diuretic therapyDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

University of Calgary

Calgary, Alberta, Canada

Outcomes

Primary Outcomes

Change in body weight

Time frame: From randomization to 96 hours after randomization

Secondary Outcomes

Total 96 hour urine output

Measured in ml urine

Time frame: From randomization to 96 hours post randomization

Subjective change in shortness of breath

As assessed by a 5 point Likert scale

Time frame: 48 hours after randomization and 96 hours post randomization

Change in renal function

Measured by estimated glomerular filtration rate

Time frame: From randomization to 7 days post randomization

Proportion of patients developing worsening renal function (WRF)

Categorical measure- need for renal replacement therapy or ultrafiltration or increase in serum creatinine by \> 26 umol/L

Time frame: From randomization to 7 days post randomization

Change in serum sodium

Measured in mmol/L

Time frame: From randomization to 7 days post randomization

Length of hospitalization

Number of days in hospital

Time frame: From hospital admission to 30 days post randomization

Need for intensive care unit admission

Categorical measure (yes/no)

Time frame: From hospital admission to 30 days post randomization

Data from ClinicalTrials.gov

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