Heart FailurePhase 2VITA-HFNCT01469988
The VO2 Increase With Testosterone Addition - Heart Failure (VITA-HF) Trial
A Phase 2 study testing Testosterone in people with Heart Failure, run by University of Alberta at 7 sites in Canada.
Trial summary
Evaluate the efficacy and safety of testosterone supplementation on functional capacity, biomarkers, quality of life and clinical outcomes for patients with heart failure. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Testosterone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 318 participants
- Where
- 7 sitesCanada
- Study dates
- Nov 2012to Apr 2014
- Phase
- Phase 2
- 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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 40 years
- NYHA Class II - III
- Left ventricular ejection fraction available by echo, nuclear or MRI < 12 months
- On optimal medical therapy (as per CCS guidelines for Chronic Heart Failure)42 for >3 months
- Female patients only: participants must be >1 year post-menopausal (defined as 12 months of spontaneous amenorrhea and confirmed by screening FSH >40 mIU/mL) OR >6 weeks post surgical bilateral oophorectomy if surgically sterilized.
Who cannot join
- Already or likely to receive LVAD or organ transplant within 6 months
- History of illicit drug use or alcohol abuse within <3 months, or history of HIV, Hepatitis B or C
- History of hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, clinically significant congenital heart disease, severe aortic or mitral regurgitation or stenosis
- Non-cardiovascular diagnosis with reduced life expectancy < 1 year including active cancer
- Recent (<1 month) cardiovascular event (admission to hospital for unstable angina, acute coronary syndrome, hypertensive crisis or ventricular arrhythmia) or cerebrovascular event (transient ischemic attack or stroke) or recent (<3 months) implantation of cardiac resynchronization therapy
- Hematocrit > 48%
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- Male patients only: PSA > 4 ng/ml, or presence of a prostate nodule
- Total serum testosterone > 350 ng/dl (12.1 nmol/L)
- Untreated severe obstructive sleep apnea per American Thoracic Society criteria
- Chronic glucocorticoid, or anabolic steroid therapy
- Chronic hemodialysis, serum creatinine > 264 umol/L (3 mg/dL) or eGFR< 15 ml/min (MDRD)
- Participation in a competing trial
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Canada7 sites
Ajax / Pickering
Ajax
Brampton (McMaster University)
Brampton
Foothills Hospital (University of Calgary)
Calgary
The University of Alberta (Mazankowski Alberta Heart Institute):
Edmonton
Surrey Memorial Hospital (University of British Columbia)
Surrey
Toronto General Hospital (University of Toronto):
Toronto
Vancouver General Hospital (University of British Columbia)
Vancouver
About this study
Evaluate the efficacy and safety of testosterone supplementation on functional capacity, biomarkers, quality of life and clinical outcomes for patients with heart failure.
Read the detailed description
Background:Heart failure is a prevalent condition of major public health importance that leads to significant morbidity and mortality despite the use of current evidence-based therapy. Further development of novel therapies to alleviate symptoms, improve functional status and ultimately clinical outcomes are needed. Cardiac function alone cannot explain all aspects of the heart failure syndrome: hence a search for peripheral mechanisms and inter-connected cardiac and non-cardiac pathways has ensued. Testosterone plays an integral role in multiple organ systems for growth, development and maintenance of health with known effects on peripheral musculature, vasculature, sympathetic tone, endothelial function and restoration of muscle metabolic function which would be beneficial in HF. Chronic HF has been associated with reduced testosterone levels, and low testosterone levels have been linked to reduced VO2, increased BNP and ANP levels, and worse clinical outcomes. Testosterone supplementation acts as a peripheral vasodilator and acutely increases cardiac output,which would improve oxygen delivery to skeletal muscles and secondarily delay transfer to anaerobic metabolism and depletion of high-energy phosphates. The increase in muscle mass associated with testosterone therapy may also result in increased endurance and decreased muscle fatigability in HF patients. Early small trials demonstrate safety, tolerability and an improvement in exercise walking distance in patients with HF. We contend that the time is now ripe for an adequately-powered phase II trial in order to test if this therapy can improve symptoms and functional status for patients with heart failure.
Specific Aim:Evaluate the efficacy and safety of testosterone supplementation on functional capacity, biomarkers, quality of life and clinical outcomes for patients with heart failure.
Synopsis:We propose a phase II randomized controlled, multi-center, double-blind trial, "The VO2Increase with Testosterone Addition - Heart Failure (VITA-HF) Trial". We plan to enroll 318 patients with chronic HF and NYHA II-III in a 1:1 trial of testosterone therapy (versus placebo): our primary objective is to test the effects on peak VO2 at 26 weeks (a commonly used surrogate outcome in phase II HFRCTthat represents both central and peripheral effects of our interventions). Given the assumptions made (a peak VO2 standard deviation of 2.7 mls/kg/min, paired t-test, and 2-sided alpha 0.05), 318 patients will have 85% power to detect a 1.0 ml/kg/min difference between the groups in the change in peak VO2 over 26 weeks. The minimally clinically important difference for peak VO2 may be as small as 0.26 mls/kg/min but is possibly higher and therefore, we have taken a conservative approach similar to that of other CIHR and NIH trials. Additional measures of quality of life, biomarkers (BNP) and clinical outcomes will be performed at 26 and 52 weeks. Quantitative measurement of core laboratory echocardiographic imaging will also assess the effect on left ventricular remodeling and markers of systolic and diastolic function. Assessment at 26 weeks will allow for the early effects to be demonstrated whereas our secondary endpoint evaluated at 52 weeks will demonstrate clinical and other outcomes important for phase III planning (including clinical, biochemical and echocardiographic endpoints).Androgel 5g was selected due to compliance and prior RCT dosing to ensure efficacy with a broad safety margin.
Feasibility:The investigators on this grant are attending physicians in large, tertiary care heart failure clinics with large patient populations and extensive experience with recruiting patients into clinical studies. The 7 sites selected have both experience and expertise in enrolling HF patients in CIHR and NIH trials.
Importance:Our proposed trial (VITA-HF) tests a novel strategic target which could enhance the quality and potentially the quantity of life of patients with heart failure by modulating complementary peripheral and central HF mechanisms.
- Conditions
- Heart Failure
- Being tested
- Testosterone
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TestosteroneDrug
Patients will be dosed accordingly: Female: 0.3g once daily (or matching placebo) gel;Males: 5g once daily (or matching placebo) gel.
| Study group | Role | What they receive |
|---|---|---|
| Testosterone | Experimental | Not described Receives: Drug: Testosterone |
| Placebo | Placebo comparator | Not described Receives: Drug: Testosterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
In patients with chronic heart failure, does 26 weeks of treatment with transdermal testosterone improve peak VO2?
The primary endpoint is change in peak VO2 measured at baseline and 26 weeks. The timing of the primary endpoint was chosen to allow for effects of either therapy to be seen within a reasonable timeframe, and to minimize loss to follow up, withdrawal due to clinical or adverse events and published data thus far supporting that an effect could be seen within 26 weeks.
Measured: 26 weeks
Secondary outcomes (2)
In patients with chronic heart failure, does 26 or 52 weeks of treatment with transdermal testosterone improve quality of life, biomarker (b-type natriuretic peptide, fasting glucose) or echocardiographic measures (LVEF, LVEDD, LVESD, SV)?
Includes total hospitalizations or ED visits (total, CV and HF), change in serum BNP at 26 and 52 weeks, change in quality of life assessed by KCCQ and FACIT-F, and changes in echocardiographic parameters (change from baseline in LVEDD, LVESD, LVEF, or SV). The FACIT-F was developed to assess fatigue, and has been validated and used in RCT. Markers of testosterone status will be evaluated to evaluate that the levels of these individual markers are attained relative to the doses used.
Measured: 52 weeks
In patients with chronic heart failure, does 52 weeks of treatment with transdermal testosterone reduce ED visits or hospitalization for heart failure, or total mortality?
Incorporates clinical endpoints and quality of life to determine if patients are improved, unchanged or worsened at 52 weeks. All patients will be ranked sequentially into a ranking stratified to 3 tiers: (1) Death [time to death from randomization date with earliest death given lowest rank]; (2) Cardiovascular hospitalization or ED visit [time to hospitalization or ED visit from randomization date, if alive]; and (3) Change in KCCQ score [if alive and no hospitalization or ED visit, then patients with least change are ranked lowest, unchanged ranked next and improvement ranked highest].
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2011 (estimated)
- Study startNov 2012
- Primary completionApr 2014
- Study completionApr 2014
Why it stopped: Feasibility
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.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 318 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Justin Ezekowitz, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01469988
- Sponsor's protocol ID
- 82-VH-01
- Acronym
- VITA-HF
- Status last verified
- Apr 2014
- First submitted
- 2 Nov 2011
- Last updated
- 23 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The VO2 Increase With Testosterone Addition - Heart Failure (VITA-HF) Trial
- ClinicalTrials.gov ID
- NCT01469988
- Acronym / sponsor ID
- VITA-HF / 82-VH-01
- Conditions
- Heart Failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Feasibility
- Enrolment
- 318 participants (estimated)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- Nov 2012
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 10 Nov 2011 (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.
Evaluate the efficacy and safety of testosterone supplementation on functional capacity, biomarkers, quality of life and clinical outcomes for patients with heart failure.
Detailed description
Background:Heart failure is a prevalent condition of major public health importance that leads to significant morbidity and mortality despite the use of current evidence-based therapy. Further development of novel therapies to alleviate symptoms, improve functional status and ultimately clinical outcomes are needed. Cardiac function alone cannot explain all aspects of the heart failure syndrome: hence a search for peripheral mechanisms and inter-connected cardiac and non-cardiac pathways has ensued. Testosterone plays an integral role in multiple organ systems for growth, development and maintenance of health with known effects on peripheral musculature, vasculature, sympathetic tone, endothelial function and restoration of muscle metabolic function which would be beneficial in HF. Chronic HF has been associated with reduced testosterone levels, and low testosterone levels have been linked to reduced VO2, increased BNP and ANP levels, and worse clinical outcomes. Testosterone supplementation acts as a peripheral vasodilator and acutely increases cardiac output,which would improve oxygen delivery to skeletal muscles and secondarily delay transfer to anaerobic metabolism and depletion of high-energy phosphates. The increase in muscle mass associated with testosterone therapy may also result in increased endurance and decreased muscle fatigability in HF patients. Early small trials demonstrate safety, tolerability and an improvement in exercise walking distance in patients with HF. We contend that the time is now ripe for an adequately-powered phase II trial in order to test if this therapy can improve symptoms and functional status for patients with heart failure.
Specific Aim:Evaluate the efficacy and safety of testosterone supplementation on functional capacity, biomarkers, quality of life and clinical outcomes for patients with heart failure.
Synopsis:We propose a phase II randomized controlled, multi-center, double-blind trial, "The VO2Increase with Testosterone Addition - Heart Failure (VITA-HF) Trial". We plan to enroll 318 patients with chronic HF and NYHA II-III in a 1:1 trial of testosterone therapy (versus placebo): our primary objective is to test the effects on peak VO2 at 26 weeks (a commonly used surrogate outcome in phase II HFRCTthat represents both central and peripheral effects of our interventions). Given the assumptions made (a peak VO2 standard deviation of 2.7 mls/kg/min, paired t-test, and 2-sided alpha 0.05), 318 patients will have 85% power to detect a 1.0 ml/kg/min difference between the groups in the change in peak VO2 over 26 weeks. The minimally clinically important difference for peak VO2 may be as small as 0.26 mls/kg/min but is possibly higher and therefore, we have taken a conservative approach similar to that of other CIHR and NIH trials. Additional measures of quality of life, biomarkers (BNP) and clinical outcomes will be performed at 26 and 52 weeks. Quantitative measurement of core laboratory echocardiographic imaging will also assess the effect on left ventricular remodeling and markers of systolic and diastolic function. Assessment at 26 weeks will allow for the early effects to be demonstrated whereas our secondary endpoint evaluated at 52 weeks will demonstrate clinical and other outcomes important for phase III planning (including clinical, biochemical and echocardiographic endpoints).Androgel 5g was selected due to compliance and prior RCT dosing to ensure efficacy with a broad safety margin.
Feasibility:The investigators on this grant are attending physicians in large, tertiary care heart failure clinics with large patient populations and extensive experience with recruiting patients into clinical studies. The 7 sites selected have both experience and expertise in enrolling HF patients in CIHR and NIH trials.
Importance:Our proposed trial (VITA-HF) tests a novel strategic target which could enhance the quality and potentially the quantity of life of patients with heart failure by modulating complementary peripheral and central HF mechanisms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Testosterone | Experimental | Drug: Testosterone |
| Placebo | Placebo comparator | Drug: Testosterone |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 40 years
- NYHA Class II - III
- Left ventricular ejection fraction available by echo, nuclear or MRI < 12 months
- On optimal medical therapy (as per CCS guidelines for Chronic Heart Failure)42 for >3 months
- Female patients only: participants must be >1 year post-menopausal (defined as 12 months of spontaneous amenorrhea and confirmed by screening FSH >40 mIU/mL) OR >6 weeks post surgical bilateral oophorectomy if surgically sterilized.
Key exclusion criteria (12 listed)
- Already or likely to receive LVAD or organ transplant within 6 months
- History of illicit drug use or alcohol abuse within <3 months, or history of HIV, Hepatitis B or C
- History of hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, clinically significant congenital heart disease, severe aortic or mitral regurgitation or stenosis
- Non-cardiovascular diagnosis with reduced life expectancy < 1 year including active cancer
- Recent (<1 month) cardiovascular event (admission to hospital for unstable angina, acute coronary syndrome, hypertensive crisis or ventricular arrhythmia) or cerebrovascular event (transient ischemic attack or stroke) or recent (<3 months) implantation of cardiac resynchronization therapy
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 |
|---|---|---|
| TestosteronePatients will be dosed accordingly: Female: 0.3g once daily (or matching placebo) gel;Males: 5g once daily (or matching placebo) gel. | Drug | Placebo, Testosterone |
Primary outcome
In patients with chronic heart failure, does 26 weeks of treatment with transdermal testosterone improve peak VO2?
Time frame: 26 weeks
The primary endpoint is change in peak VO2 measured at baseline and 26 weeks. The timing of the primary endpoint was chosen to allow for effects of either therapy to be seen within a reasonable timeframe, and to minimize loss to follow up, withdrawal due to clinical or adverse events and published data thus far supporting that an effect could be seen within 26 weeks.
2 secondary outcomes
In patients with chronic heart failure, does 26 or 52 weeks of treatment with transdermal testosterone improve quality of life, biomarker (b-type natriuretic peptide, fasting glucose) or echocardiographic measures (LVEF, LVEDD, LVESD, SV)?
Time frame: 52 weeks
In patients with chronic heart failure, does 52 weeks of treatment with transdermal testosterone reduce ED visits or hospitalization for heart failure, or total mortality?
Time frame: 52 weeks
Results and safety
The study was stopped early (reason given: Feasibility). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2018.
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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.
Justin Ezekowitz principal investigator
University of Alberta
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Testosterone in people with Heart Failure, run by University of Alberta at 7 sites 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 12 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 23 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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: Feasibility). 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?
In patients with chronic heart failure, does 26 weeks of treatment with transdermal testosterone improve peak VO2? (time frame: 26 weeks). 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 23 Jan 2018; AzTrials last refreshed its copy on 6 Nov 2026.