NCT01813201

Benefit of the Treatment With Testosterone in Chronic Heart Failure Testosterone Deficiency Subjects

A Randomized and Double-blind Study to Evaluate the Benefit of the Treatment With Testosterone in Chronic Heart Failure Testosterone Deficiency Subjects

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this clinical trial is to determine whether intermittent administration of testosterone against placebo is associated with a reduction of mortality and heart failure hospitalizations at 1 year, in male patients with advanced heart failure and testosterone deficiency.

Detailed description

Heart Failure (HF) represents one of the major social and health problems, for its high prevalence and its huge economic impact, as well as the elevated morbidity and mortality associated. In Spain, the estimated prevalence is 7% over 45 years old, and it increases until 18% over 75 years old. Currently, HF is the leading cause of hospital admission over 65 years and the mortality for patients with symptomatic HF remains worse than the majority of cancers. The estimated minimum expenditure is 1.1% of total health care costs and 2% of specialized medical care. This accounts for a staggeringly large financial burden on the health care system. Chronic HF is a complex disease, whose progression involves multiple pathophysiological systems. It is well established the deleterious effect of activation of renin-angiotensin-aldosterone and sympathetic nervous systems. The blockage of these systems by beta-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs) and aldosterone antagonists has improved prognosis. However, in spite of these therapies, the prognosis of patients with chronic HF remains poor. During the HF progression to advanced stages, it has been shown an anabolic and metabolic deterioration, resulting in a predominance of catabolic processes. The deficiency of anabolic hormones correlates with greater severity of symptoms, activation of neuroendocrine and inflammatory systems, insulin resistance, metabolic impairment, exercise intolerance, anemia and cardiac cachexia. All these processes take part of the final progression of the HF disease until death, when HF becomes a systemic disease. In men with HF, levels of testosterone (the main anabolic hormone) are decreased; in fact, 30% of men have levels below the 10th percentile of a reference healthy population adjusted for age. The deterioration of anabolic hormones correlates inversely with the severity of HF disease and it determines a higher mortality. In fact, low testosterone levels are associated with reduced cardiac output, greater symptomatic limitation and higher mortality. Therefore, testosterone deficiency in men with HF has a detrimental impact on symptoms and prognosis. In addition, testosterone has shown to have beneficial effects on HF patients, such as vasodilatation of coronary and peripheral arteries, inotropic effects, reduction of neurohormonal activation, anti-inflammatory and immunomodulatory actions, reduction of cytokine production and improvement of muscle strength. All these actions have a potential benefit in patients with HF, because they are involved in the progression of the disease, especially at advanced stages. The rational approach "testosterone replacement for improving the prognosis of patients with advanced HF and testosterone deficiency" has strong pathophysiological plausibility. To date, no other clinical trials have evaluated the effect of testosterone replacement on morbidity and mortality. However, in the last years, numerous editorials in leading journals have concluded on the need to clarify the effect of testosterone therapy on cardiac function and the morbimortality in patients with advanced HF. Our group has worked in the last years in this field, confirming the presence of a testosterone deficiency in men with chronic HF, which is associated with a worse prognosis and a greater decline in exercise capacity. Therefore, the investigators propose a clinical trial of morbimortality in a population with advanced heart failure and associated deficiency on testosterone; in which, the previous background justifies the potential benefit of testosterone replacement therapy. In addition, the large clinical impact of this disease supports the priority need of an independent study.

Conditions

• Heart Failure

Interventions

Type	Name	Description
DRUG	Testosterone undecanoate	Testosterone undecanoate intramuscular long-acting, 1000 mg/dose, administered at inclusion and every 12 weeks for 9 months (4 dose) (testosterone group) against the administration of placebo (saline isotonic solution).
DRUG	Saline isotonic solution	Saline isotonic solution (placebo)intramuscular,administered at inclusion and every 12 weeks for 9 months (4 dose)

Timeline

• Start date: 2011-03-01
• Primary completion: 2014-03-01
• Completion: 2014-03-01
• First posted: 2013-03-18
• Last updated: 2017-12-13

Locations

1 site across 1 country: Spain