Back to resultsTolvaptan for Advanced or Refractory Heart Failure
Primary Purpose
Heart Failure, Hyponatremia
Status
Terminated
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Tolvaptan
Standard of care diuretic therapy
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure
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
Sites / Locations
- University of Calgary
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Tolvaptan
Standard of care diuretic therapy
Arm Description
Tolvaptan 15-60 mg, once daily for 4 days or until hospital discharge
Usual standard of care diuretic therapy for patients with acute decompensated heart failure
Outcomes
Primary Outcome Measures
Change in body weight
Secondary Outcome Measures
Total 96 hour urine output
Measured in ml urine
Subjective change in shortness of breath
As assessed by a 5 point Likert scale
Change in renal function
Measured by estimated glomerular filtration rate
Proportion of patients developing worsening renal function (WRF)
Categorical measure- need for renal replacement therapy or ultrafiltration or increase in serum creatinine by > 26 umol/L
Change in serum sodium
Measured in mmol/L
Length of hospitalization
Number of days in hospital
Need for intensive care unit admission
Categorical measure (yes/no)
Need for positive inotropic agent use
Categorical measure (yes/no)
Composite of Worsening Renal Function or need for inotropic agent
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
Categorical outcome (yes/no)
Clinical markers of congestion
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)
Measurement calculated in absolute value of NT-pro-BNP
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02959411
Brief Title
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
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Terminated
Why Stopped
Low accrual rate
Study Start Date
October 2016 (undefined)
Primary Completion Date
June 30, 2020 (Actual)
Study Completion Date
June 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Calgary
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Hyponatremia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tolvaptan
Arm Type
Experimental
Arm Description
Tolvaptan 15-60 mg, once daily for 4 days or until hospital discharge
Arm Title
Standard of care diuretic therapy
Arm Type
Active Comparator
Arm Description
Usual standard of care diuretic therapy for patients with acute decompensated heart failure
Intervention Type
Drug
Intervention Name(s)
Tolvaptan
Other Intervention Name(s)
Samsca
Intervention Description
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
Intervention Name(s)
Standard of care diuretic therapy
Intervention Description
Usual standard of care diuretic therapy for patients hospitalized with acute decompensated heart failure
Primary Outcome Measure Information:
Title
Change in body weight
Time Frame
From randomization to 96 hours after randomization
Secondary Outcome Measure Information:
Title
Total 96 hour urine output
Description
Measured in ml urine
Time Frame
From randomization to 96 hours post randomization
Title
Subjective change in shortness of breath
Description
As assessed by a 5 point Likert scale
Time Frame
48 hours after randomization and 96 hours post randomization
Title
Change in renal function
Description
Measured by estimated glomerular filtration rate
Time Frame
From randomization to 7 days post randomization
Title
Proportion of patients developing worsening renal function (WRF)
Description
Categorical measure- need for renal replacement therapy or ultrafiltration or increase in serum creatinine by > 26 umol/L
Time Frame
From randomization to 7 days post randomization
Title
Change in serum sodium
Description
Measured in mmol/L
Time Frame
From randomization to 7 days post randomization
Title
Length of hospitalization
Description
Number of days in hospital
Time Frame
From hospital admission to 30 days post randomization
Title
Need for intensive care unit admission
Description
Categorical measure (yes/no)
Time Frame
From hospital admission to 30 days post randomization
Title
Need for positive inotropic agent use
Description
Categorical measure (yes/no)
Time Frame
From randomization to 7 days post randomization
Title
Composite of Worsening Renal Function or need for inotropic agent
Description
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)
Time Frame
From randomization to 7 days post randomization
Title
30 day cardiovascular death and/or hospitalization
Description
Categorical outcome (yes/no)
Time Frame
From Randomization to 30 days post randomization
Title
Clinical markers of congestion
Description
Described as total number of the presence of Jugular venous pressure (JVP) level, edema, rales, orthopnea, 3rd heart sound
Time Frame
From randomization to 96 hours after randomization
Title
Change in N-terminal brain natriuretic peptide (NT-pro BNP)
Description
Measurement calculated in absolute value of NT-pro-BNP
Time Frame
From randomization to 96 hours post randomization compared to baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan Howlett, MD
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
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Tolvaptan for Advanced or Refractory Heart Failure
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