JOCARDITE: JOint Use of Database to Identify Risk Factors of CARDio-vascular Toxicity Induced by Immune Checkpoint Inhibitors
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Myocarditis and other cardiovascular toxicities ICI-related 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
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)
Other Names:
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| Non case Non-case will be patients exposed to ICI without cardiovascular toxicities |
Drug: ICI
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)
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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
- 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. [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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Case reported in the World Health Organization (WHO) database of individual safety case reports to 01/01/2025
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Case reported in the APHP Entrepot de Données de Santé (EDS) database of individual safety case reports to 01/01/2025
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Case reported in the Système National Des Données de Santé (SNDS) Database of individual safety case reports to 01/01/2025
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Case reported in a retrospective international multicenter registry of ICI-associated myocarditis to 01/01/2025
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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)
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM. | Paris | France | 75013 |
Sponsors and Collaborators
- Groupe Hospitalier Pitie-Salpetriere
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Bonaca MP, Olenchock BA, Salem JE, Wiviott SD, Ederhy S, Cohen A, Stewart GC, Choueiri TK, Di Carli M, Allenbach Y, Kumbhani DJ, Heinzerling L, Amiri-Kordestani L, Lyon AR, Thavendiranathan P, Padera R, Lichtman A, Liu PP, Johnson DB, Moslehi J. Myocarditis in the Setting of Cancer Therapeutics: Proposed Case Definitions for Emerging Clinical Syndromes in Cardio-Oncology. Circulation. 2019 Jul 2;140(2):80-91. Review.
- Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018 Mar 10;391(10124):933. doi: 10.1016/S0140-6736(18)30533-6.
- Salem JE, Allenbach Y, Vozy A, Brechot N, Johnson DB, Moslehi JJ, Kerneis M. Abatacept for Severe Immune Checkpoint Inhibitor-Associated Myocarditis. N Engl J Med. 2019 Jun 13;380(24):2377-2379. doi: 10.1056/NEJMc1901677.
- Salem JE, Manouchehri A, Moey M, Lebrun-Vignes B, Bastarache L, Pariente A, Gobert A, Spano JP, Balko JM, Bonaca MP, Roden DM, Johnson DB, Moslehi JJ. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol. 2018 Dec;19(12):1579-1589. doi: 10.1016/S1470-2045(18)30608-9. Epub 2018 Nov 12.
- CIC1421-20-03