Heart FailurePhase 4NCT02959411
Tolvaptan for Advanced or Refractory Heart Failure
A Phase 4 study testing Tolvaptan in people with Heart Failure and Hyponatremia, run by University of Calgary at 1 site in Canada.
Trial summary
This study will clarify the clinical usefulness of Tolvaptan therapy in patients with complicated acute decompensated heart failure and hyponatremia (low blood sodium). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Hyponatremia
- What is being tested?
- Tolvaptan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2016to 30 Jun 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Tolvaptan for the Management of Acute Decompensated Heart Failure in Patients With Advanced or Refractory Heart Failure
This study will clarify the clinical usefulness of Tolvaptan therapy in patients with complicated acute decompensated heart failure and hyponatremia (low blood sodium).
Read the 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
- Being tested
- Tolvaptan, Standard of care diuretic therapy
- Medical subject headings
- Heart Failure, Hyponatremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
Also called Samsca
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 therapyDrug
Usual standard of care diuretic therapy for patients hospitalized with acute decompensated heart failure
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan | Experimental | Tolvaptan 15-60 mg, once daily for 4 days or until hospital discharge Receives: Drug: Tolvaptan |
| Standard of care diuretic therapy | Active comparator | Usual standard of care diuretic therapy for patients with acute decompensated heart failure Receives: Drug: Standard of care diuretic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in body weight
Measured: From randomization to 96 hours after randomization
Secondary outcomes (12)
Total 96 hour urine output
Measured in ml urine
Measured: From randomization to 96 hours post randomization
Subjective change in shortness of breath
As assessed by a 5 point Likert scale
Measured: 48 hours after randomization and 96 hours post randomization
Change in renal function
Measured by estimated glomerular filtration rate
Measured: From randomization to 7 days post randomization
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
Measured: From randomization to 7 days post randomization
Change in serum sodium
Measured in mmol/L
Measured: From randomization to 7 days post randomization
Length of hospitalization
Number of days in hospital
Measured: From hospital admission to 30 days post randomization
Need for intensive care unit admission
Categorical measure (yes/no)
Measured: From hospital admission to 30 days post randomization
Need for positive inotropic agent use
Categorical measure (yes/no)
Measured: From randomization to 7 days post randomization
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)
Measured: From randomization to 7 days post randomization
30 day cardiovascular death and/or hospitalization
Categorical outcome (yes/no)
Measured: From Randomization to 30 days post randomization
Clinical markers of congestion
Described as total number of the presence of Jugular venous pressure (JVP) level, edema, rales, orthopnea, 3rd heart sound
Measured: From randomization to 96 hours after randomization
Change in N-terminal brain natriuretic peptide (NT-pro BNP)
Measurement calculated in absolute value of NT-pro-BNP
Measured: From randomization to 96 hours post randomization compared to baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2016 (estimated)
- Study startOct 2016
- Primary completion30 Jun 2020
- Study completion30 Jun 2020
Why it stopped: Low accrual rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Jonathan Howlett, University of Calgary
- Investigators
- Jonathan Howlett, MD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02959411
- Sponsor's protocol ID
- REB16-0064
- Status last verified
- Jul 2020
- First submitted
- 17 Oct 2016
- Last updated
- 27 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tolvaptan for the Management of Acute Decompensated Heart Failure in Patients With Advanced or Refractory Heart Failure
- ClinicalTrials.gov ID
- NCT02959411
- Acronym / sponsor ID
- REB16-0064
- Conditions
- Heart Failure, Hyponatremia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual rate
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- Oct 2016
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 9 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan | Experimental | Drug: TolvaptanTolvaptan 15-60 mg, once daily for 4 days or until hospital discharge |
| Standard of care diuretic therapy | Active comparator | Drug: Standard of care diuretic therapyUsual standard of care diuretic therapy for patients with acute decompensated heart failure |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TolvaptanAlso: SamscaTolvaptan 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. | Drug | Tolvaptan |
| Standard of care diuretic therapyUsual standard of care diuretic therapy for patients hospitalized with acute decompensated heart failure | Drug | Standard of care diuretic therapy |
Primary outcome
Change in body weight
Time frame: From randomization to 96 hours after randomization
12 secondary outcomes
Total 96 hour urine output
Time frame: From randomization to 96 hours post randomization
Subjective change in shortness of breath
Time frame: 48 hours after randomization and 96 hours post randomization
Change in renal function
Time frame: From randomization to 7 days post randomization
Proportion of patients developing worsening renal function (WRF)
Time frame: From randomization to 7 days post randomization
Change in serum sodium
Time frame: From randomization to 7 days post randomization
Length of hospitalization
Time frame: From hospital admission to 30 days post randomization
Need for intensive care unit admission
Time frame: From hospital admission to 30 days post randomization
Need for positive inotropic agent use
Time frame: From randomization to 7 days post randomization
Composite of Worsening Renal Function or need for inotropic agent
Time frame: From randomization to 7 days post randomization
30 day cardiovascular death and/or hospitalization
Time frame: From Randomization to 30 days post randomization
Clinical markers of congestion
Time frame: From randomization to 96 hours after randomization
Change in N-terminal brain natriuretic peptide (NT-pro BNP)
Time frame: From randomization to 96 hours post randomization compared to baseline
Results and safety
The study was stopped early (reason given: Low accrual rate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2020.
- Individual participant dataSharing planned: No
Related trials for Heart Failure
RecruitingPhase 2/3
Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Left Ventricular Systolic Dysfunction (MK-1242-036)
Heart Failure, Left Ventricular Systolic Dysfunction
RecruitingPhase 1/2
HS235 Study in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction
Pulmonary Hypertension, Heart Failure With Preserved Ejection Fraction
Active, not recruiting
Heart Failure Patient Management and Interventions Using Continuous Patient Monitoring Outside Hospitals and Real-world Data
Chronic Heart Failure, Heart Transplant Recipient
Enrolling by invitationObservational study
Multi-Scale Analysis of Phenotypes in Heart Failure (MAP-HEART)
Heart Failure
Not yet recruitingObservational study
Real-world Effectiveness and Safety of Savagen (Sacubitril/Valsartan) in Malaysian HFrEF Patients
Heart Failure With Reduced Ejection Fraction (HFrEF), Heart Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan Howlett, MD principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tolvaptan in people with Heart Failure and Hyponatremia, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low accrual rate). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in body weight (time frame: From randomization to 96 hours after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2020.