Heart Failure
Conditions
Brief summary
Heart failure (HF) is a complex condition resulting from structural or functional heart diseases that impair the ability of the heart to fill with or pump out blood. The main manifestations of HF are shortness of breath and tiredness which may limit the ability to exercise or perform simple daily physical activities such as walking. Heart disease leading to HF is associated with reduced muscle mass and reduced strength and low blood levels of testosterone; a hormone normally produced by the human (male and female) body. Recent studies have shown improvements of symptoms and ability to exercise in patients with heart failure receiving testosterone. This is a placebo controlled study to determine the efficacy and safety of low dose testosterone (300 and 450 microgram/day) delivered by a transdermal system (patch) in women with significant HF.
Interventions
DRUGplacebo
placebo patch
DRUGtestosterone
300 or 450 micrograms/day transdermal testosterone patch
Sponsors
Warner Chilcott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female 50 years of age or older; post-menopausal (≥ 12 Mo/ from last menstruation) * Documented left ventricular ejection fraction (LVEF) of 20-40% within 90 days prior to the baseline visit * History of HF for more than 90 days and a diagnosis of symptomatic HF (Class III NYHA) for at least 30 days prior to the baseline visit * Ambulatory (i.e., able to walk without assistance of another person or device such as cane or walker)
Exclusion criteria
* Neuromuscular or rheumatologic conditions that limit the to their ability to improve walking distance * Pulmonary edema or multiorgan failure or cardiogenic shock within 30 days prior to the baseline visit * Congenital heart disease, infiltrative myocardial disease * Unstable angina or myocardial infarction within 30 days prior to the baseline visit * Undiagnosed abnormal genital bleeding * History of breast cancer, breast surgery, or breast disease contraindicating estrogen/hormone therapy * Polycystic ovary syndrome or any other condition known to be adversely affected by testosterone treatment * Resting heart rate \> 120 bpm * Systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 100 mmHg * Known or suspected hypersensitivity or allergy to any adhesive or to any of the components of the testosterone transdermal system (TTS) * Use of SERMS, SARMS, SPRMs, tibolone, testosterone, estrogen, progesterone agonists and antagonists or taking any prescription and over the counter medications/ nutraceuticals (eg, phyto-estrogens) that may have anabolic or steroid hormonal effects within 30 days prior to the baseline visit * Use of marketed or investigational oral, sub-lingual, topical, transdermal injectable, or vaginal androgen therapy including dehydroepiandrosterone (DHEA) at any time within 3 months prior to the baseline visit * Use of systemic corticosteroids within 30 days prior to the baseline visit (acute use for fewer than 7 days is acceptable)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Six Minute Walking Test (6MWT), Meters | Baseline and Day 180 | Measurement of distance walked as fast as possible on a hard flat pathway in six minutes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Severity of Heart Failure (HF) as Measured by New York Heart Association (NYHA) Classification | Baseline and Day 180 | Class I: Cardiac disease w/o limitation of physical activity. Class II: Cardiac disease resulting in slight limitation of physical activity. Comfortable at rest; ordinary activity results in fatigue, palpitation, dyspnea or anginal pain. Class III: Cardiac disease resulting in marked limitation of physical activity. Comfortable at rest; less than ordinary activity causes fatigue, palpitation, dyspnea or anginal pain. Class IV: Cardiac disease resulting in inability to carry on any physical activity w/o discomfort. Symptoms present at rest. Any physical activity increases discomfort. |
| Mortality or Hospitalizations | Baseline and Day 180 | Composite endpoint - patients who were hospitalized or died during the trial. |
| Percent Change Minnesota Living With Heart Failure Questionnaire (MLHFQ) Overall Score and Domain Scores | Baseline and Day 180 | Minnesota Living with Heart Failure Questionnaire assessing how much heart failure affects life during previous month. Three scales measuring physical dimension (8 items, score 0-40), emotional dimension (5 items, score 0-25) and overall score (all 21 items, score 0-105). Eight separate items measure social & economic impairments included as part of overall score. |
| Percent Change Patient Global Assessment of Heart Failure Status | Baseline and Day 180 | Four global questions classifying improvement or deterioration in heart failure - Since your last clinic vist, has there been any change in activity limitation / symptoms / emotions / overall quality of life, related to your heart failure? Scale -7/very great deal worse, -6 great deal worse, -5 good deal worse, -4 moderately worse, -3 somewhat worse, -2 a little worse, -1 hardly any worse/almost the same, 0 no change, 1 hardly better/almost the same, 2 little better, 3 somewhat better, 4 moderately better, 5 good deal better, 6 great deal better, 7 very great deal better. |
| Percent Change Physician Global Assessment of Heart Failure Status | Baseline and Day 180 | Physician rates improvement or deterioration in heart failure: Scale -7/very great deal worse, -6 great deal worse, -5 good deal worse, -4 moderately worse, -3 somewhat worse, -2 a little worse, -1 hardly any worse/almost the same, 0 no change, 1 hardly better/almost the same, 2 little better, 3 somewhat better, 4 moderately better, 5 good deal better, 6 great deal better, 7 very great deal better. |
Countries
United States
Participant flow
Recruitment details
6 month trial, screening started 22 Sep 2009 and ended 24 Mar 2010.
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo patch | 6 |
| 300 µg/Day Testosterone 300 micrograms/day transdermal testosterone patch | 4 |
| 450 µg/Day Testosterone 450 micrograms/day transdermal testosterone patch | 7 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 |
| Overall Study | Sponsor Terminated Study | 6 | 1 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | 300 µg/Day Testosterone | 450 µg/Day Testosterone | Total |
|---|---|---|---|---|
| Age Continuous | 70.3 years STANDARD_DEVIATION 6.2 | 69.8 years STANDARD_DEVIATION 5 | 74.3 years STANDARD_DEVIATION 9 | 71.8 years STANDARD_DEVIATION 7.2 |
| Region of Enrollment United States | 6 participants | 4 participants | 7 participants | 17 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 7 Participants | 17 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 6 | 2 / 4 | 4 / 7 |
| serious Total, serious adverse events | 2 / 6 | 0 / 4 | 2 / 7 |
Outcome results
Primary
Percent Change From Baseline in Six Minute Walking Test (6MWT), Meters
Measurement of distance walked as fast as possible on a hard flat pathway in six minutes
Time frame: Baseline and Day 180
Population: No statistical analysis performed due to early termination of the study. Study was stopped prior to any subjects reaching a timepoint for efficacy assessment. Safety results were available and recorded in the interim.
Secondary
Mortality or Hospitalizations
Composite endpoint - patients who were hospitalized or died during the trial.
Time frame: Baseline and Day 180
Population: No statistical analysis performed due to early termination of the study. Study was stopped prior to any subjects reaching a timepoint for efficacy assessment. Safety results were available and recorded in the interim.
Secondary
Percent Change From Baseline in Severity of Heart Failure (HF) as Measured by New York Heart Association (NYHA) Classification
Class I: Cardiac disease w/o limitation of physical activity. Class II: Cardiac disease resulting in slight limitation of physical activity. Comfortable at rest; ordinary activity results in fatigue, palpitation, dyspnea or anginal pain. Class III: Cardiac disease resulting in marked limitation of physical activity. Comfortable at rest; less than ordinary activity causes fatigue, palpitation, dyspnea or anginal pain. Class IV: Cardiac disease resulting in inability to carry on any physical activity w/o discomfort. Symptoms present at rest. Any physical activity increases discomfort.
Time frame: Baseline and Day 180
Population: No statistical analysis performed due to early termination of the study. Study was stopped prior to any subjects reaching a timepoint for efficacy assessment. Safety results were available and recorded in the interim.
Secondary
Percent Change Minnesota Living With Heart Failure Questionnaire (MLHFQ) Overall Score and Domain Scores
Minnesota Living with Heart Failure Questionnaire assessing how much heart failure affects life during previous month. Three scales measuring physical dimension (8 items, score 0-40), emotional dimension (5 items, score 0-25) and overall score (all 21 items, score 0-105). Eight separate items measure social & economic impairments included as part of overall score.
Time frame: Baseline and Day 180
Population: No statistical analysis performed due to early termination of the study. Study was stopped prior to any subjects reaching a timepoint for efficacy assessment. Safety results were available and recorded in the interim.
Secondary
Percent Change Patient Global Assessment of Heart Failure Status
Four global questions classifying improvement or deterioration in heart failure - Since your last clinic vist, has there been any change in activity limitation / symptoms / emotions / overall quality of life, related to your heart failure? Scale -7/very great deal worse, -6 great deal worse, -5 good deal worse, -4 moderately worse, -3 somewhat worse, -2 a little worse, -1 hardly any worse/almost the same, 0 no change, 1 hardly better/almost the same, 2 little better, 3 somewhat better, 4 moderately better, 5 good deal better, 6 great deal better, 7 very great deal better.
Time frame: Baseline and Day 180
Population: No statistical analysis performed due to early termination of the study. Study was stopped prior to any subjects reaching a timepoint for efficacy assessment. Safety results were available and recorded in the interim.
Secondary
Percent Change Physician Global Assessment of Heart Failure Status
Physician rates improvement or deterioration in heart failure: Scale -7/very great deal worse, -6 great deal worse, -5 good deal worse, -4 moderately worse, -3 somewhat worse, -2 a little worse, -1 hardly any worse/almost the same, 0 no change, 1 hardly better/almost the same, 2 little better, 3 somewhat better, 4 moderately better, 5 good deal better, 6 great deal better, 7 very great deal better.
Time frame: Baseline and Day 180
Population: No statistical analysis performed due to early termination of the study. Study was stopped prior to any subjects reaching a timepoint for efficacy assessment. Safety results were available and recorded in the interim.