Tolvaptan for Advanced or Refractory Heart Failure
- Conditions
- Heart FailureHyponatremia
- Interventions
- Drug: Standard of care diuretic therapy
- Registration Number
- NCT02959411
- Lead Sponsor
- University of Calgary
- Brief Summary
This study will clarify the clinical usefulness of Tolvaptan therapy in patients with complicated acute decompensated heart failure and hyponatremia (low blood sodium).
- Detailed 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 9
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard of care diuretic therapy Standard of care diuretic therapy Usual standard of care diuretic therapy for patients with acute decompensated heart failure Tolvaptan Tolvaptan Tolvaptan 15-60 mg, once daily for 4 days or until hospital discharge
- Primary Outcome Measures
Name Time Method Change in body weight From randomization to 96 hours after randomization
- Secondary Outcome Measures
Name Time Method Need for intensive care unit admission From hospital admission to 30 days post randomization Categorical measure (yes/no)
Total 96 hour urine output From randomization to 96 hours post randomization Measured in ml urine
Proportion of patients developing worsening renal function (WRF) From randomization to 7 days post randomization Categorical measure- need for renal replacement therapy or ultrafiltration or increase in serum creatinine by \> 26 umol/L
Length of hospitalization From hospital admission to 30 days post randomization Number of days in hospital
Need for positive inotropic agent use From randomization to 7 days post randomization Categorical measure (yes/no)
Composite of Worsening Renal Function or need for inotropic agent From randomization to 7 days post randomization Worsening Renal Function defined as increase from serum creatinine at randomization of more than 30 umol/L at any time from randomization to 7 days. This is a categorical outcome (yes/no)
30 day cardiovascular death and/or hospitalization From Randomization to 30 days post randomization Categorical outcome (yes/no)
Clinical markers of congestion From randomization to 96 hours after randomization Described as total number of the presence of Jugular venous pressure (JVP) level, edema, rales, orthopnea, 3rd heart sound
Subjective change in shortness of breath 48 hours after randomization and 96 hours post randomization As assessed by a 5 point Likert scale
Change in renal function From randomization to 7 days post randomization Measured by estimated glomerular filtration rate
Change in serum sodium From randomization to 7 days post randomization Measured in mmol/L
Change in N-terminal brain natriuretic peptide (NT-pro BNP) From randomization to 96 hours post randomization compared to baseline Measurement calculated in absolute value of NT-pro-BNP
Trial Locations
- Locations (1)
University of Calgary
🇨🇦Calgary, Alberta, Canada