CardioTOxicity Induced by andRogeNICS and Their Antagonists (TORNICS)

Completed

• Conditions: Heart Diseases

• Registration Number: NCT03193138
• Lead Sponsor: Groupe Hospitalier Pitie-Salpetriere

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.

Study Timeline

• Study Start: 2017-06-07
• Study First Submitted: 2017-06-12
• Study First Submitted QC: 2017-06-16
• Study First Posted: 2017-06-20
• Primary Completion: 2017-06-21
• Study Completion: 2017-06-21
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-24
• Last Update Posted: 2019-09-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 3096

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.	Immediate evaluation	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
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.	Immediate evaluation	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
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.	Immediate evaluation	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Centre Régional de Pharmaco-vigilance - Paris, Pitié-Salpétrière; 🇫🇷 Paris, Ile De France, France