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

Cardiotoxicity of Abiraterone in the National French Pharmacovigilance Database and in the European Clinical Trials Database (EudraCT)

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.

Study Overview

• Status: Completed
• Conditions: Arrhythmias, Cardiac; Tachycardia, Supraventricular; Cardiac Failure; Atrial Fibrillation and Flutter
• Intervention / Treatment: Drug: L02 (sex hormones used in treatment of neoplastic diseases) and G03 (sex hormones)

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.

• Study Type: Observational
• Enrollment (Actual): 1717

Contacts and Locations

Study Locations

• France
  • Ile De France
    • Paris, Ile De France, France, 75013
      • Centre Régional de Pharmaco-vigilance - Paris, Pitié-Salpétrière

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• 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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of disproportionality of reports for cardiotoxicity associated with abiraterone as compared to enzalutamide by performing a case- non-case study	Analysis of disproportionality of reports for cardiotoxicity associated with abiraterone as compared to enzalutamide by performing a case- non-case study	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the reporting of suspected drug-induced supraventricular arrhythmias with abiraterone as compared to enzalutamide by performing a disproportionality analysis	Compare the reporting of suspected drug-induced supraventricular arrhythmias with abiraterone as compared to enzalutamide by performing a disproportionality analysis	2 months
Compare the reporting of drug-induced cardiac failure with abiraterone as compared to enzalutamide by performing a disproportionality analysis	Compare the reporting of drug-induced cardiac failure with abiraterone as compared to enzalutamide by performing a disproportionality analysis	2 months
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	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	2 months
Description of other mineralocorticoid related adverse events (hypokaliemia, fluid retention, and hypertension) when the cardio toxicity occurs	Description of other mineralocorticoid related adverse events (hypokaliemia, fluid retention, and hypertension) when the cardio toxicity occurs	2 months
Description of the population of patients having a cardio-vascular adverse event	Description of the population of patients having a cardio-vascular adverse event	2 months
Description of the duration of treatment when the toxicity happens (role of cumulative dose)	Description of the duration of treatment when the toxicity happens (role of cumulative dose)	2 months
Description of the drug-drug interactions associated with adverse events	Description of the drug-drug interactions associated with adverse events	2 months
Causality assessment of reported cardiovascular events according to the WHO-UMC system	Causality assessment of reported cardiovascular events according to the WHO-UMC system	2 months

Collaborators and Investigators

• Sponsor: Groupe Hospitalier Pitie-Salpetriere

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2017
• Primary Completion (Actual): July 13, 2017
• Study Completion (Actual): July 13, 2017

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: August 4, 2017
• First Posted (Actual): August 9, 2017

Study Record Updates

• Last Update Posted (Actual): October 18, 2018
• Last Update Submitted That Met QC Criteria: October 17, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Cardiotoxicity; abiraterone acetate; androgen antagonist
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Wounds and Injuries; Cardiac Conduction System Disease; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Heart Failure; Atrial Fibrillation; Arrhythmias, Cardiac; Tachycardia; Cardiotoxicity; Tachycardia, Supraventricular; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: CIC1421-17-08

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No