cARdiotoxicity Profile of aBIraTeRone in prostAte Cancer : a pharmacoviGilancE Study

Arrhythmias, Cardiac Clinical Trial

— ARBITRAGE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03243604
• Other study ID #: CIC1421-17-08
• Status: Completed
• Start date: May 16, 2017
• Est. completion date: July 13, 2017

Study information

• Verified date: October 2018
• Source: Groupe Hospitalier Pitie-Salpetriere
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1717
• Est. completion date: July 13, 2017
• Est. primary completion date: July 13, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Atrial Fibrillation
• Atrial Fibrillation and Flutter
• Atrial Flutter
• Cardiac Failure
• Cardiotoxicity
• Heart Failure
• Tachycardia
• Tachycardia, Supraventricular

Intervention

Drug:
• L02 (sex hormones used in treatment of neoplastic diseases) and G03 (sex hormones)
Androgen-deprivation therapies including L02 (sex hormones used in treatment of neoplastic diseases), and G03 (sex hormones)

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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Description of the drug-drug interactions associated with adverse events	Description of the drug-drug interactions associated with adverse events	2 months
Secondary	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