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

Study Overview
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Brief Summary
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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
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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

Official Title
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JOint Use of Database to Identify Risk Factors of CARDio-vascular Adverse Reactions Induced by Immune Checkpoint InhibiTors: VigiBase, Entrepot de Données de Santé (EDS), Système National Des Données de Santé (SNDS) Databases and a Retrospective International Multicenter Registry of ICI-associated Myocarditis

Conditions
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Vasculitis, Myocarditis, Cardiomyopathies, Heart Diseases, Cardiovascular Diseases, Pericarditis

Intervention / Treatment
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* Drug: ICI


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Myocarditis and other cardiovascular toxicities ICI-related<br>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 | Drug: ICI<br>* Immune checkpoint inhibitor targeting either PD-1, PD-L1 or CTLA-4, and included in the ATC following list (ATC classification): Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC3)<br>* Other names: Immune checkpoint inhibitors;|
| Non case<br>Non-case will be patients exposed to ICI without cardiovascular toxicities | Drug: ICI<br>* Immune checkpoint inhibitor targeting either PD-1, PD-L1 or CTLA-4, and included in the ATC following list (ATC classification): Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC3)<br>* Other names: Immune checkpoint inhibitors;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identifying risk factors of cardio-vascular toxicity of ICIs. | Identifying risk factors of overreporting of cardiovascular adverse events in ICI treated patients | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 | 
| 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 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 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 | 
| Cardio-vascular toxicity of ICIs. | Number of patients with cardiovascular adverse events with significant over-reporting 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 | 
| 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug-induced cardiotoxicity, Immune Checkpoint Inhibitors, Anti-PD-1, Anti-PD-L1, Anti CTLA-4