CardioTOxicity Induced by andRogeNICS and Their Antagonists (TORNICS)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Cardiotoxicity of Androgenic Agonists and Antagonists in the National French Pharmacovigilance Database and EudraCT Database

Conditions
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Heart Diseases

Intervention / Treatment
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* Drug: Hormonal therapies: G03, H01C and L02 in the ATC classification


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Hormonal therapies: G03, H01C and L02 in the ATC classification|Hormonal therapies including all therapies classified G03, H01C and L02 in the ATC classification|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | The research includes the report with MedDRA terms: System Organ Class (SOC) Cardiac Disorders and High Level Term (HLT) Death and Sudden Death. Drugs investigated are hormonal therapies with the reference G03 in the ATC classification | Immediate evaluation | 
| 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. | The research includes the report with MedDRA terms: System Organ Class (SOC) Cardiac Disorders and High Level Term (HLT) Death and Sudden Death. Drugs investigated are hormonal therapies with the reference H01C in the ATC classification | Immediate evaluation | 
| 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. | The research includes the report with MedDRA terms: System Organ Class (SOC) Cardiac Disorders and High Level Term (HLT) Death and Sudden Death. Drugs investigated are hormonal therapies with the reference L02 in the ATC classification | Immediate evaluation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Causality assessment of reported cardiovascular events | Causality assessment of reported cardiovascular events according to the WHO-UMC system | Immediate evaluation | 
| Type of cardiotoxicity depending on the category and type of hormonal therapy | Description of the type of cardiotoxicity depending on the category and type of hormonal therapy | Immediate evaluation | 
| Duration of treatment when the toxicity happens | Description of the duration of treatment when the toxicity happens (role of cumulative dose) | Immediate evaluation | 
| Drug-drug interactions associated with adverse events | Description of the drug-drug interactions associated with adverse events (particularly heart failure, ischemic heart disease and cardiac arrhythmia's) | Immediate evaluation | 
| Pathologies for which the incriminated drugs have been prescribed | Description of the pathologies (cancer, hormonal insufficiency) for which the incriminated drugs have been prescribed | Immediate evaluation | 
| Population of patients having a cardio-vascular adverse event | Description of the population of patients having a cardio-vascular adverse event | Immediate evaluation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiotoxicity, Androgens, Hormone Replacement Therapy, Testosterone, Androgen Antagonists