JOint Use of Database to Identify Risk Factors of CARDio-vascular Toxicity Induced by Immune Checkpoint Inhibitors

Recruiting

• Conditions: Pericarditis; Vasculitis; Cardiovascular Diseases; Myocarditis; Cardiomyopathies; Heart Diseases
• Interventions: Drug: ICI

• Registration Number: NCT04294771
• Lead Sponsor: Groupe Hospitalier Pitie-Salpetriere

Brief Summary

Immune checkpoint inhibitors (ICIs) might induce high grade immune-related adverse events (irAEs) involving the cardio-vascular system. This study investigates reports of cardio-vascular toxicity associated with treatment including anti-PD1, Anti-PDL-1, and Anti CTLA4 classes using the World Health Organization (WHO) database VigiBase, Assistance Publique Hopitaux de Paris Entrepot de Données de Santé (APHP.EDS), French Système National Des Données de Santé (SNDS) Databases and a retrospective international multicenter registry of ICI-associated myocarditis

Detailed Description

ICIs have dramatically improved clinical outcomes in multiple cancer types and are increasingly being tested in earlier disease settings and in combination. Thus, irAEs can occur and risk factors for such events have been scarcely described. Here, the investigators will use VigiBase (http://www.vigiaccess.org/), the World Health Organization (WHO) database of individual safety case reports, to identify risk factors for cases of cardiovascular adverse drug reaction following treatment with ICIs, the investigators will also use two french databases : APHP Entrepot de Données de Santé (EDS), French Système National Des Données de Santé (SNDS) Databases and a retrospective international multicenter registry of ICI-associated myocarditis

Study Timeline

• Study Start: 2019-01-01
• Study First Submitted: 2020-03-02
• Study First Submitted QC: 2020-03-02
• Study First Posted: 2020-03-04
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-14
• Last Update Posted: 2023-09-15
• Primary Completion: 2025-01-01
• Study Completion: 2025-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500000

Inclusion Criteria

• Case reported in the World Health Organization (WHO) database of individual safety case reports to 01/01/2025
• Case reported in the APHP Entrepot de Données de Santé (EDS) database of individual safety case reports to 01/01/2025
• Case reported in the Système National Des Données de Santé (SNDS) Database of individual safety case reports to 01/01/2025
• Case reported in a retrospective international multicenter registry of ICI-associated myocarditis to 01/01/2025
• 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), Cemiplimab (L01XC33)

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 and other cardiovascular toxicities ICI-related	ICI	Case reported in the World Health Organization (WHO)international pharmacovigilance database, or APHP Entrepot de Données de Santé (EDS) and French Système National Des Données de Santé (SNDS) Databases, with a chronology compatible with the drug toxicity
Non case	ICI	Non-case will be patients exposed to ICI without cardiovascular toxicities

Primary Outcome Measures

Name	Time	Method
Identifying risk factors of cardio-vascular toxicity of ICIs.	Case reported in VigiBase, APHP Entrepot de Données de Santé (EDS), Système National Des Données de Santé (SNDS) Databases and a retrospective international multicenter registry of ICI-associated myocarditis from inception to January 2025	Identifying risk factors of overreporting of cardiovascular adverse events in ICI treated patients

Secondary Outcome Measures

Name	Time	Method
Causality assessment of reported cardiovascular events	Case reported in VigiBase, APHP Entrepot de Données de Santé (EDS), Système National Des Données de Santé (SNDS) Databases and a retrospective international multicenter registry of ICI-associated myocarditis from inception to January 2025
Description of the drug-drug interactions associated with adverse events	Case reported in VigiBase, APHP Entrepot de Données de Santé (EDS), Système National Des Données de Santé (SNDS) Databases and a retrospective international multicenter registry of ICI-associated myocarditis from inception to January 2025
Description of the duration of treatment when the toxicity happens (role of cumulative dose)	Case reported in VigiBase, APHP Entrepot de Données de Santé (EDS), Système National Des Données de Santé (SNDS) Databases and a retrospective international multicenter registry of ICI-associated myocarditis from inception to January 2025
Description of the pathologies (cancer) for which the incriminated drugs have been prescribed	Case reported in VigiBase, APHP Entrepot de Données de Santé (EDS), Système National Des Données de Santé (SNDS) Databases and a retrospective international multicenter registry of ICI-associated myocarditis from inception to January 2025
Description of the population of patients having a cardio-vascular adverse event	Case reported in VigiBase, APHP Entrepot de Données de Santé (EDS), Système National Des Données de Santé (SNDS) Databases and a retrospective international multicenter registry of ICI-associated myocarditis from inception to January 2025
Description and added predictive value of electrocardiographic, echocardiographic, cardiac and muscle pathology, cardiac MRI and positron emission tomograph (PET) manifestations in patients with ICI associated myocarditis	Case reported in VigiBase, APHP Entrepot de Données de Santé (EDS), Système National Des Données de Santé (SNDS) Databases and a retrospective international multicenter registry of ICI-associated myocarditis from inception to January 2025	Description and added predictive value of electrocardiographic, echocardiographic, cardiac and muscle pathology, cardiac MRI and positron emission tomograph (PET) manifestations in patients with ICI associated myocarditis
Description of the type of cardiotoxicity depending on the category of ICIs	Case reported in VigiBase, APHP Entrepot de Données de Santé (EDS), Système National Des Données de Santé (SNDS) Databases and a retrospective international multicenter registry of ICI-associated myocarditis from inception to January 2025
Cardio-vascular toxicity of ICIs.	Case reported in VigiBase, APHP Entrepot de Données de Santé (EDS), Système National Des Données de Santé (SNDS) Databases and a retrospective international multicenter registry of ICI-associated myocarditis from inception to January 2025	Number of patients with cardiovascular adverse events with significant over-reporting ICIs

Trial Locations

Locations (1)

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