Tolvaptan for Advanced or Refractory Heart Failure

NCT ID: NCT02959411

Last Updated: 2020-07-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2020-06-30

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.

Conditions

Heart Failure; Hyponatremia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tolvaptan

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

Group Type: EXPERIMENTAL

Tolvaptan

Intervention Type: DRUG

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 therapy

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

Group Type: ACTIVE_COMPARATOR

Standard of care diuretic therapy

Intervention Type: DRUG

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

Interventions

Tolvaptan

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.

Intervention Type: DRUG

Standard of care diuretic therapy

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

Intervention Type: DRUG

Other Intervention Names

Samsca

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Dr. Jonathan Howlett

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jonathan Howlett, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

University of Calgary

Calgary, Alberta, Canada

Countries

Canada

Other Identifiers

REB16-0064

Identifier Type: -

Identifier Source: org_study_id