Heart Failure, Hyponatremia
Conditions
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.
Interventions
DRUGTolvaptan
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.
DRUGStandard of care diuretic therapy
Usual standard of care diuretic therapy for patients hospitalized with acute decompensated heart failure
Sponsors
University of Calgary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in body weight | From randomization to 96 hours after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Change in serum sodium | From randomization to 7 days post randomization | Measured in mmol/L |
| Length of hospitalization | From hospital admission to 30 days post randomization | Number of days in hospital |
| Total 96 hour urine output | From randomization to 96 hours post randomization | Measured in ml urine |
| 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 |
| 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 |
| Need for intensive care unit admission | From hospital admission to 30 days post randomization | Categorical measure (yes/no) |
Countries
Canada
Outcome results
None listed