CardioTOxicity Induced by andRogeNICS and Their Antagonists (TORNICS)

Heart Diseases Clinical Trial

— TORNICS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03193138
• Other study ID #: CIC1421-17-06
• Status: Completed
• Start date: June 7, 2017
• Est. completion date: June 21, 2017

Study information

• Verified date: September 2019
• Source: Groupe Hospitalier Pitie-Salpetriere
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3096
• Est. completion date: June 21, 2017
• Est. primary completion date: June 21, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiotoxicity
• Heart Diseases

Intervention

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

Locations

Country	Name	City	State
France	Centre Régional de Pharmaco-vigilance - Paris, Pitié-Salpétrière	Paris	Ile De France

Sponsors (1)

Lead Sponsor	Collaborator
Groupe Hospitalier Pitie-Salpetriere

Country where clinical trial is conducted

France, 

References & Publications (3)

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. — View 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 Reversibl — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Causality assessment of reported cardiovascular events	Causality assessment of reported cardiovascular events according to the WHO-UMC system	Immediate evaluation
Secondary	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
Secondary	Duration of treatment when the toxicity happens	Description of the duration of treatment when the toxicity happens (role of cumulative dose)	Immediate evaluation
Secondary	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
Secondary	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
Secondary	Population of patients having a cardio-vascular adverse event	Description of the population of patients having a cardio-vascular adverse event	Immediate evaluation