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

Phase 2

Terminated

Conditions: Heart Failure

Interventions: Drug: placebo
Drug: testosterone

Registration Number: NCT00957034

Lead Sponsor: Warner Chilcott

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 17

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	placebo	placebo patch
300 µg/day testosterone	testosterone	300 micrograms/day transdermal testosterone patch
450 µg/day testosterone	testosterone	450 micrograms/day transdermal testosterone patch

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.