Tolvaptan for Advanced or Refractory Heart Failure

NCT02959411 | Terminated Phase 4

• 1 other identifier: REB16-0064
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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).

Conditions

Heart Failure; Hyponatremia

Outcome Measures

Primary Outcomes (1)

• Change in body weight

  From randomization to 96 hours after randomization

Secondary Outcomes (12)

• Total 96 hour urine output

  From randomization to 96 hours post randomization

• Subjective change in shortness of breath

  48 hours after randomization and 96 hours post randomization

• Change in renal function

  From randomization to 7 days post randomization

• Proportion of patients developing worsening renal function (WRF)

  From randomization to 7 days post randomization

• Change in serum sodium

  From randomization to 7 days post randomization

Study Arms (2)

Tolvaptan

EXPERIMENTAL

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

Drug: Tolvaptan

Standard of care diuretic therapy

ACTIVE COMPARATOR

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

Drug: Standard of care diuretic therapy

Interventions

Tolvaptan 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.

Also known as: Samsca

Tolvaptan

Standard of care diuretic therapy DRUG

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

Standard of care diuretic therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

MeSH Terms

Conditions

Heart Failure; Hyponatremia

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jonathan Howlett, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: October 17, 2016
• First Posted: November 9, 2016
• Study Start: October 1, 2016
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: July 27, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)