Clinical trial NCT02959411: Tolvaptan for Advanced or Refractory Heart Failure
Official title: Tolvaptan for the Management of Acute Decompensated Heart Failure in Patients With Advanced or Refractory Heart Failure
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Heart Failure
Hyponatremia
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2016-11-09
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in body weight
timeFrame: From randomization to 96 hours after randomization
Secondary outcomes:
measure: Total 96 hour urine output
timeFrame: From randomization to 96 hours post randomization
measure: Subjective change in shortness of breath
timeFrame: 48 hours after randomization and 96 hours post randomization
measure: Change in renal function
timeFrame: From randomization to 7 days post randomization
measure: Proportion of patients developing worsening renal function (WRF)
timeFrame: From randomization to 7 days post randomization
measure: Change in serum sodium
timeFrame: From randomization to 7 days post randomization
measure: Length of hospitalization
timeFrame: From hospital admission to 30 days post randomization
measure: Need for intensive care unit admission
timeFrame: From hospital admission to 30 days post randomization
measure: Need for positive inotropic agent use
timeFrame: From randomization to 7 days post randomization
measure: Composite of Worsening Renal Function or need for inotropic agent
timeFrame: From randomization to 7 days post randomization
measure: 30 day cardiovascular death and/or hospitalization
timeFrame: From Randomization to 30 days post randomization
measure: Clinical markers of congestion
timeFrame: From randomization to 96 hours after randomization
measure: Change in N-terminal brain natriuretic peptide (NT-pro BNP)
timeFrame: From randomization to 96 hours post randomization compared to baseline
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Jonathan Howlett, MD
role: PRINCIPAL_INVESTIGATOR
References: