Clinical trial NCT03243604: cARdiotoxicity Profile of aBIraTeRone in prostAte Cancer : a pharmacoviGilancE Study
Official title: Cardiotoxicity of Abiraterone in the National French Pharmacovigilance Database and in the European Clinical Trials Database (EudraCT)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Arrhythmias, Cardiac
Atrial Fibrillation and Flutter
Tachycardia, Supraventricular
Cardiac Failure
Keywords: Cardiotoxicity
abiraterone acetate
androgen antagonist
Lead sponsor: Groupe Hospitalier Pitie-Salpetriere
Sponsor class: OTHER
First posted: 2017-08-09
Enrollment: 1717
Sex: MALE
Minimum age (years): 18
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 May 2017 and included patients treated with hormonal therapies included in the ATC L02, and G03

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Analysis of disproportionality of reports for cardiotoxicity associated with abiraterone as compared to enzalutamide by performing a case- non-case study
timeFrame: 2 months
Secondary outcomes:
measure: Compare the reporting of suspected drug-induced supraventricular arrhythmias with abiraterone as compared to enzalutamide by performing a disproportionality analysis
timeFrame: 2 months
measure: Compare the reporting of drug-induced cardiac failure with abiraterone as compared to enzalutamide by performing a disproportionality analysis
timeFrame: 2 months
measure: Compare the reporting of drug-induced cardiac failure and/or supraventricular arrhythmias with abiraterone as compared to other androgen-deprivation therapies by performing a disproportionality analysis
timeFrame: 2 months
measure: Description of other mineralocorticoid related adverse events (hypokaliemia, fluid retention, and hypertension) when the cardio toxicity occurs
timeFrame: 2 months
measure: Description of the population of patients having a cardio-vascular adverse event
timeFrame: 2 months
measure: Description of the duration of treatment when the toxicity happens (role of cumulative dose)
timeFrame: 2 months
measure: Description of the drug-drug interactions associated with adverse events
timeFrame: 2 months
measure: Causality assessment of reported cardiovascular events according to the WHO-UMC system
timeFrame: 2 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Centre Régional de Pharmaco-vigilance - Paris, Pitié-Salpétrière
state: Ile De France
Study officials:
References: