cARdiotoxicity Profile of aBIraTeRone in prostAte Cancer : a pharmacoviGilancE Study (ARBITRAGE)

Groupe Hospitalier Pitie-Salpetriere

Status: Completed

Conditions: Tachycardia, Supraventricular; Cardiac Failure; Atrial Fibrillation and Flutter; Arrhythmias, Cardiac

Treatments: Drug: L02 (sex hormones used in treatment of neoplastic diseases) and G03 (sex hormones)

Study type: Observational

Funder types: Other

Identifiers

NCT03243604

CIC1421-17-08

Details and patient eligibility

About

Abiraterone associated with prednisone is used in prostate cancer. Abiraterone is a selective small-molecule inhibiting cytochrome P450 17A1 (CYP17A1), a key enzyme in androgen synthesis.

CYP17A inhibition is also responsible for mineral corticosteroid related adverse events as hypokaliemia, fluid retention, and hypertension. Primary hyperaldosteronism is associated with cardiovascular toxicities such as atrial fibrillation and cardiac failure. Other androgen-deprivation therapies are not associated with increased mineral corticosteroid level.

This study investigates reports of cardiovascular toxicities for treatment including L02 (sex hormones used in treatment of neoplastic diseases), and G03 (sex hormones) used in prostate cancer in the French pharmacovigilance database and in the EudraCT database.

Full description

Due to its peculiar pharmacology, abiraterone is potentially associated with more cardiotoxicity as compared to other androgen-deprivation therapies. This study investigates the main characteristics of patients affected by cardiovascular side effects of which supraventricular arrhythmias (including atrial fibrillation, atrial flutter, supraventricular tachycardia), and cardiac failure imputed to drugs classified as L02, and G03 according to anatomical therapeutic chemical (ATC) classification. A causality assessment according to the World Health Organization-The Uppsala Monitoring Centre (WHO-UMC) is systematically applied.

Enrollment: 1,717 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Case reported in the French pharmacovigilance database from 01/01/1985 to 16/05/2017
• Case reported in the EudraCT database to May 2017
• Adverse event reported were including the MedDRA terms: SOC Cardiac Disorders; SOC Vascular Disorders; HLT Death, Sudden Death; HLGT Water, electrolyte and mineral investigations; HLGT Cardiac and vascular investigations (excl enzyme tests); and PT Syncope.
• Patients treated with hormonal therapies included in the ATC L02, and G03

Exclusion criteria

• Chronology not compatible between the drug and the toxicity