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

NCT01813201 | Completed Phase 4 DMC

• 2 other identifiers: TIC-09112009-016498-13
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heart Failure

Keywords

Testosterone; Anabolic deterioration

Outcome Measures

Primary Outcomes (1)

• Death

  Death from any cause or hospitalization for heart failure or decompensation of heart failure requiring intravenous drug for stabilization.

  1 year

Secondary Outcomes (5)

• Mortality

  1 year

• Hospital readmissions for any reason.

  1 year

• Number of decompensated heart failure who have required intravenous medication for stabilization.

  1 year

• Changes in test quality of life (Minnesota Living Heart Failure) and clinical modified Framingham score.

  1 year

• Changes in cardiac function parameters assessed by echocardiography and natriuretic peptide (NT)-proBNP concentration.

  1 year

Study Arms (2)

Testosterone undecanoate

ACTIVE COMPARATOR

Testosterone undecanoate intramuscular long-acting, 1000 mg/dose, administered at inclusion and every 12 weeks for 9 months (4 dose)

Drug: Testosterone undecanoate

Saline isotonic solution (Placebo)

PLACEBO COMPARATOR

Placebo (saline isotonic solution)administered at inclusion and every 12 weeks for 9 months (4 dose) (control group).

Drug: Saline isotonic solution

Interventions

Testosterone undecanoate DRUG

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).

Also known as: Reandron®

Testosterone undecanoate

Saline isotonic solution DRUG

Saline isotonic solution (placebo)intramuscular,administered at inclusion and every 12 weeks for 9 months (4 dose)

Saline isotonic solution (Placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least one hospital admission for HF.
• Stable clinical status, New York Heart Association (NYHA) functional class II-IV.
• Left ventricular ejection fraction of less than 40%
• NT-proBNP concentration greater than 1000 pg / ml.
• Total testosterone and free testosterone deficiency measured in the last month
• Age \>18 years.
• Patients who have given their written informed consent.

You may not qualify if:

• No informed consent.
• Taking oral anticoagulants
• Severe valvular heart disease with an indication for surgical repair.
• Extracardiac disease with an estimated prognosis of less than 1 year.
• History of androgen-dependent prostate cancer, benign prostate hyperplasia treatment or prostate-specific antigen (PSA)\> 3 ng / ml.
• History of breast carcinoma or liver tumor
• Severe renal impairment (glomerular filtration rate \<30 ml / kg / min).
• Acute coronary syndrome in the last year
• Renal or hepatic failure
• Uncontrolled hypertension
• Erythrocytosis (hematocrit\> 5%)
• Hypersensitivity to testosterone or any excipients.

Sponsors & Collaborators

• Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia: lead
• Hospital Universitario Virgen de la Arrixaca: collaborator
• Germans Trias i Pujol Hospital: collaborator

Study Sites (1)

Cardiology Service, Hospital Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Related Publications (21)

• Rodriguez-Artalejo F, Banegas Banegas JR, Guallar-Castillon P. [Epidemiology of heart failure]. Rev Esp Cardiol. 2004 Feb;57(2):163-70. Spanish.

  PMID: 14967113 BACKGROUND

• Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM; Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004 May 20;350(21):2140-50. doi: 10.1056/NEJMoa032423.

  PMID: 15152059 BACKGROUND

• Pugh PJ, English KM, Jones TH, Channer KS. Testosterone: a natural tonic for the failing heart? QJM. 2000 Oct;93(10):689-94. doi: 10.1093/qjmed/93.10.689. No abstract available.

  PMID: 11029481 BACKGROUND

• Malkin C, Jones T, Channer K. Testosterone in chronic heart failure. Front Horm Res. 2009;37:183-196. doi: 10.1159/000176053.

  PMID: 19011297 BACKGROUND

• Pugh PJ, Jones RD, Jones TH, Channer KS. Heart failure as an inflammatory condition: potential role for androgens as immune modulators. Eur J Heart Fail. 2002 Dec;4(6):673-80. doi: 10.1016/s1388-9842(02)00162-9.

  PMID: 12453536 BACKGROUND

• Anker SD, Al-Nasser FO. Chronic heart failure as a metabolic disorder. Heart Fail Monit. 2000;1(2):42-9.

  PMID: 12634873 BACKGROUND

• Anker SD, Chua TP, Ponikowski P, Harrington D, Swan JW, Kox WJ, Poole-Wilson PA, Coats AJ. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation. 1997 Jul 15;96(2):526-34. doi: 10.1161/01.cir.96.2.526.

  PMID: 9244221 BACKGROUND

• Kontoleon PE, Anastasiou-Nana MI, Papapetrou PD, Alexopoulos G, Ktenas V, Rapti AC, Tsagalou EP, Nanas JN. Hormonal profile in patients with congestive heart failure. Int J Cardiol. 2003 Feb;87(2-3):179-83. doi: 10.1016/s0167-5273(02)00212-7.

  PMID: 12559538 BACKGROUND

• Moriyama Y, Yasue H, Yoshimura M, Mizuno Y, Nishiyama K, Tsunoda R, Kawano H, Kugiyama K, Ogawa H, Saito Y, Nakao K. The plasma levels of dehydroepiandrosterone sulfate are decreased in patients with chronic heart failure in proportion to the severity. J Clin Endocrinol Metab. 2000 May;85(5):1834-40. doi: 10.1210/jcem.85.5.6568.

  PMID: 10843161 BACKGROUND

• Jankowska EA, Biel B, Majda J, Szklarska A, Lopuszanska M, Medras M, Anker SD, Banasiak W, Poole-Wilson PA, Ponikowski P. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006 Oct 24;114(17):1829-37. doi: 10.1161/CIRCULATIONAHA.106.649426. Epub 2006 Oct 9.

  PMID: 17030678 BACKGROUND

• Jankowska EA, Filippatos G, Ponikowska B, Borodulin-Nadzieja L, Anker SD, Banasiak W, Poole-Wilson PA, Ponikowski P. Reduction in circulating testosterone relates to exercise capacity in men with chronic heart failure. J Card Fail. 2009 Jun;15(5):442-50. doi: 10.1016/j.cardfail.2008.12.011. Epub 2009 Feb 10.

  PMID: 19477405 BACKGROUND

• P Peñafiel, DA Pascual, B. Redondo, P Nicolas, PL Tornel, J Sanchez-Mas, G de la Morena, M Valdés. Anabolic deficiency as determinant of functional impairment and prognosis in heart failure patients. European journal of Heart Failure 2007;6(supl 1):146.

  BACKGROUND

• Pugh PJ, Jones TH, Channer KS. Acute haemodynamic effects of testosterone in men with chronic heart failure. Eur Heart J. 2003 May;24(10):909-15. doi: 10.1016/s0195-668x(03)00083-6.

  PMID: 12714022 BACKGROUND

• Malkin CJ, Jones TH, Channer KS. The effect of testosterone on insulin sensitivity in men with heart failure. Eur J Heart Fail. 2007 Jan;9(1):44-50. doi: 10.1016/j.ejheart.2006.04.006. Epub 2006 Jul 7.

  PMID: 16828341 BACKGROUND

• Rauchhaus M, Doehner W, Anker SD. Heart failure therapy: testosterone replacement and its implications. Eur Heart J. 2006 Jan;27(1):10-2. doi: 10.1093/eurheartj/ehi653. Epub 2005 Nov 16. No abstract available.

  PMID: 16291772 BACKGROUND

• Pugh PJ, Jones RD, West JN, Jones TH, Channer KS. Testosterone treatment for men with chronic heart failure. Heart. 2004 Apr;90(4):446-7. doi: 10.1136/hrt.2003.014639. No abstract available.

  PMID: 15020527 BACKGROUND

• Malkin CJ, Pugh PJ, West JN, van Beek EJ, Jones TH, Channer KS. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Eur Heart J. 2006 Jan;27(1):57-64. doi: 10.1093/eurheartj/ehi443. Epub 2005 Aug 10.

  PMID: 16093267 BACKGROUND

• Caminiti G, Volterrani M, Iellamo F, Marazzi G, Massaro R, Miceli M, Mammi C, Piepoli M, Fini M, Rosano GM. Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol. 2009 Sep 1;54(10):919-27. doi: 10.1016/j.jacc.2009.04.078.

  PMID: 19712802 BACKGROUND

• Aukrust P, Ueland T, Gullestad L, Yndestad A. Testosterone: a novel therapeutic approach in chronic heart failure? J Am Coll Cardiol. 2009 Sep 1;54(10):928-9. doi: 10.1016/j.jacc.2009.05.039. No abstract available.

  PMID: 19712803 BACKGROUND

• Pascual-Figal DA, Tornel PL, Valdes M. Letter by Pascual-Figal et al regarding article, "Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival". Circulation. 2007 May 29;115(21):e548; author reply e549. doi: 10.1161/CIRCULATIONAHA.106.685040. No abstract available.

  PMID: 17533191 BACKGROUND

• Navarro-Penalver M, Perez-Martinez MT, Gomez-Bueno M, Garcia-Pavia P, Lupon-Roses J, Roig-Minguell E, Comin-Colet J, Bayes-Genis A, Noguera JA, Pascual-Figal DA. Testosterone Replacement Therapy in Deficient Patients With Chronic Heart Failure: A Randomized Double-Blind Controlled Pilot Study. J Cardiovasc Pharmacol Ther. 2018 Nov;23(6):543-550. doi: 10.1177/1074248418784020. Epub 2018 Jun 21.

  PMID: 29929385 DERIVED

Related Links

• MeSH Terms
• Spanish Cardiology Society

MeSH Terms

Conditions

Heart Failure

Interventions

testosterone undecanoate

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Domingo A Pascual-Figal, MD, PhD

  Hospital Universitario Virgen Arrixaca

  PRINCIPAL INVESTIGATOR

• Antoni Bayes-Genis, MD, PhD

  Germans Trias i Pujol Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2011
• First Posted: March 18, 2013
• Study Start: March 1, 2011
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: December 13, 2017

Record last verified: 2014-11

Locations

ES (1)