Clinical trial NCT03193138: CardioTOxicity Induced by andRogeNICS and Their Antagonists (TORNICS)
Official title: Cardiotoxicity of Androgenic Agonists and Antagonists in the National French Pharmacovigilance Database and EudraCT Database
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Diseases
Keywords: Cardiotoxicity
Androgens
Hormone Replacement Therapy
Testosterone
Androgen Antagonists
Lead sponsor: Groupe Hospitalier Pitie-Salpetriere
Sponsor class: OTHER
First posted: 2017-06-20
Enrollment: 3096
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The population is selected in the French pharmacovigilance database and EudraCT database from 01/01/1985 to 14/04/2017 and included patients treated with hormonal therapies included in the ATC classification references: G03, H01C and L02.

Brief summary: Anti-androgenic therapies relying on peripheral and/or central blockade for the treatment of prostate cancer seems to have an impact on the cardio-vascular system. This study investigates reports of cardiovascular toxicities for treatment including Anatomical Therapeutic Chemical (ATC) classification: sex hormones (G03), hypothalamic hormones (H01C) and sex hormones used in treatment of neoplastic diseases (L02) in the French pharmacovigilance database and European Clinical Trials (EudraCT) database.

Detailed description: Hormone replacement therapies and contraceptive pills are responsible of a wide range of cardio-vascular side effects, particularly thrombo-embolic disorders and ischemic heart disease. The difference of incidence and type of cardio-vascular events between men and women are strongly related to sex hormones. Androgenic agonists and antagonists are used in various indication including prostate cancer or hormone replacement therapies. This study investigates the main characteristics of patients affected by cardiovascular side effects (of which ventricular arrhythmia's, QT prolongation and Torsade de Pointe) imputed to drugs classified as G03, H01C and L02 according to ATC. A causality assessment according to both Begaud's method and the World Health Organization-The Uppsala Monitoring Centre (WHO-UMC) is systematically applied.

Eligibility criteria: Inclusion Criteria:

* Case reported in the French pharmacovigilance database and EudraCT database from 01/01/1985 to 14/04/2017
* Adverse event reported were including the MedDRA terms: SOC Cardiac Affections and the HLT Death and Sudden Death
* Patients treated with hormonal therapies included in the ATC classification references: G03, H01C and L02

Exclusion Criteria:

* Chronology not compatible between the drug and the toxicity

Primary outcomes:
measure: Identification and report of the cardio-vascular toxicity of anti-androgenic therapies (reference G03 in the ATC classification) with a causality assessment using Begaud's and WHO's method.
timeFrame: Immediate evaluation
measure: Identification and report of the cardio-vascular toxicity of anti-androgenic therapies (reference H01C in the ATC classification) with a causality assessment using Begaud's and WHO's method.
timeFrame: Immediate evaluation
measure: Identification and report of the cardio-vascular toxicity of anti-androgenic therapies (reference L02 in the ATC classification) with a causality assessment using Begaud's and WHO's method.
timeFrame: Immediate evaluation
Secondary outcomes:
measure: Causality assessment of reported cardiovascular events
timeFrame: Immediate evaluation
measure: Type of cardiotoxicity depending on the category and type of hormonal therapy
timeFrame: Immediate evaluation
measure: Duration of treatment when the toxicity happens
timeFrame: Immediate evaluation
measure: Drug-drug interactions associated with adverse events
timeFrame: Immediate evaluation
measure: Pathologies for which the incriminated drugs have been prescribed
timeFrame: Immediate evaluation
measure: Population of patients having a cardio-vascular adverse event
timeFrame: Immediate evaluation
Other outcomes:
Locations:
city: Paris
country: France
facility: Centre Régional de Pharmaco-vigilance - Paris, Pitié-Salpétrière
state: Ile De France
Study officials:
References:
citation: Salem JE, Yang T, Moslehi JJ, Waintraub X, Gandjbakhch E, Bachelot A, Hidden-Lucet F, Hulot JS, Knollmann BC, Lebrun-Vignes B, Funck-Brentano C, Glazer AM, Roden DM. Androgenic Effects on Ventricular Repolarization: A Translational Study From the International Pharmacovigilance Database to iPSC-Cardiomyocytes. Circulation. 2019 Sep 24;140(13):1070-1080. doi: 10.1161/CIRCULATIONAHA.119.040162. Epub 2019 Aug 5.
citation: Salem JE, Waintraub X, Courtillot C, Shaffer CM, Gandjbakhch E, Maupain C, Moslehi JJ, Badilini F, Haroche J, Gougis P, Fressart V, Glazer AM, Hidden-Lucet F, Touraine P, Lebrun-Vignes B, Roden DM, Bachelot A, Funck-Brentano C. Hypogonadism as a Reversible Cause of Torsades de Pointes in Men. Circulation. 2018 Jul 3;138(1):110-113. doi: 10.1161/CIRCULATIONAHA.118.034282. No abstract available.
citation: Barber M, Nguyen LS, Wassermann J, Spano JP, Funck-Brentano C, Salem JE. Cardiac arrhythmia considerations of hormone cancer therapies. Cardiovasc Res. 2019 Apr 15;115(5):878-894. doi: 10.1093/cvr/cvz020.
citation: Salem JE, Yang T, Moslehi JJ, Waintraub X, Gandjbakhch E, Bachelot A, Hidden-Lucet F, Hulot JS, Knollmann BC, Lebrun-Vignes B, Funck-Brentano C, Glazer AM, Roden DM. Androgenic effects on ventricular repolarization: A translational study from the international pharmacovigilance database to iPSC-cardiomyocytes. Ann Endocrinol (Paris). 2021 Jun;82(3-4):132-133. doi: 10.1016/j.ando.2020.02.008. Epub 2020 Feb 29.