Assessing the Safety/Efficacy of Transdermal Testosterone in Female Patients With Symptomatic Heart Failure

Study Overview
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Brief Summary
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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.

Official Title
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A Placebo-controlled Study to Determine the Efficacy and Safety of 300 and 450 µg/Day Transdermal Testosterone in Female Patients With Low Ejection Fraction and Symptomatic Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: placebo
* Drug: testosterone


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>placebo patch | Drug: placebo<br>* placebo patch<br>|
| Experimental: 300 µg/day testosterone<br>300 micrograms/day transdermal testosterone patch | Drug: testosterone<br>* 300 or 450 micrograms/day transdermal testosterone patch<br>|
| Experimental: 450 µg/day testosterone<br>450 micrograms/day transdermal testosterone patch | Drug: testosterone<br>* 300 or 450 micrograms/day transdermal testosterone patch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Baseline and Day 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Day 180 | 
| Mortality or Hospitalizations | Composite endpoint - patients who were hospitalized or died during the trial. | Baseline and Day 180 | 
| 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. | Baseline and Day 180 | 
| 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. | Baseline and Day 180 | 
| 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. | Baseline and Day 180 |