Evaluation of Reporting of Immune Checkpoint Inhibitor Associated Cardio-vascular Adverse Reactions

Completed

• Conditions: Cardiac Complication; Myocarditis
• Interventions: Drug: ICI

• Registration Number: NCT03387540
• Lead Sponsor: Groupe Hospitalier Pitie-Salpetriere

Brief Summary

Immune checkpoint inhibitors (ICIs) might have high grade immune-related adverse events (irAEs) on the cardio-vascular system. This study investigates reports of cardio-vascular toxicity with treatment including anti-PD1, Anti-PDL-1, and Anti CTLA4 classes using the World Health Organization (WHO) database VigiBase.

Detailed Description

ICIs have dramatically improved clinical outcomes in multiple cancer types and are increasingly being tested in earlier disease settings and used in combination. However, irAEs can occur. Here the investigators use VigiBase (http://www.vigiaccess.org/), the World Health Organization (WHO) database of individual safety case reports, to identify cases of cardiovascular adverse drug reaction following treatment with ICIs.

Study Timeline

• Study Start: 2017-12-02
• Primary Completion: 2017-12-04
• Study First Submitted: 2017-12-22
• Study First Submitted QC: 2017-12-22
• Study Completion: 2017-12-31
• Study First Posted: 2018-01-02
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-24
• Last Update Posted: 2019-09-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 104

Inclusion Criteria

• Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
• Adverse event reported were including the MedDRA terms: Cardiac and vascular investigations (excl enzyme tests) (HLGT), Vascular disorders (SOC), Skeletal and cardiac muscle analyses (HLT), Sudden death (PT), Sudden cardiac death (PT), Cardiac disorders (SOC), Cardiac arrhythmias (HLGT), Cardiac disorder signs and symptoms (HLGT), Cardiac neoplasms (HLGT), Cardiac valve disorders (HLGT), Congenital cardiac disorders (HLGT), Coronary artery disorders (HLGT), Endocardial disorders (HLGT), Heart failures (HLGT), Myocardial disorders (HLGT), Pericardial disorders (HLGT)
• Patients treated with ICIs included in the ATC: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).

Exclusion Criteria

• Chronology not compatible between the drug and the toxicity

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Myocarditis induced by Immune check point inhibitor	ICI	Case reported in the World Health Organization (WHO) of myocarditis of patient treated by ICI, with a chronology compatible with the drug toxicity

Primary Outcome Measures

Name	Time	Method
Cardio-vascular toxicity of ICIs.	Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017	Identification and report of the cardio-vascular toxicity of ICIs. The research includes the report with MedDRA terms: SOC Cardiac Disorders, SOC Vascular Disorders, Sudden death (PT), Cardiac and vascular investigations (excl enzyme tests) (HLGT), Skeletal and cardiac muscle analyses (HLT). Drugs investigated are ICIs: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).

Secondary Outcome Measures

Name	Time	Method
Description of the duration of treatment when the toxicity happens (role of cumulative dose)	Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the drug-drug interactions associated with adverse events	Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the population of patients having a cardio-vascular adverse event	Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Causality assessment of reported cardiovascular events according to the WHO system	Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the type of cardiotoxicity depending on the category of ICIs	Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Description of the pathologies (cancer) for which the incriminated drugs have been prescribed	Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

Trial Locations

Locations (1)

AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.; 🇫🇷 Paris, France