Clinical trial NCT04294771: JOint Use of Database to Identify Risk Factors of CARDio-vascular Toxicity Induced by Immune Checkpoint Inhibitors
Official title: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Myocarditis
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Pericarditis
Vasculitis
Keywords: Drug-induced cardiotoxicity
Immune Checkpoint Inhibitors
Anti-PD-1
Anti-PD-L1
Anti CTLA-4
Lead sponsor: Groupe Hospitalier Pitie-Salpetriere
Sponsor class: OTHER
First posted: 2020-03-04
Enrollment: 500000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients treated with an ICI for a cancer

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

Eligibility criteria: 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

Primary outcomes:
measure: Identifying risk factors of cardio-vascular toxicity of ICIs.
timeFrame: 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 outcomes:
measure: Causality assessment of reported cardiovascular events
timeFrame: 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
measure: Description of the type of cardiotoxicity depending on the category of ICIs
timeFrame: 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
measure: Description of the duration of treatment when the toxicity happens (role of cumulative dose)
timeFrame: 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
measure: Description of the drug-drug interactions associated with adverse events
timeFrame: 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
measure: Description of the pathologies (cancer) for which the incriminated drugs have been prescribed
timeFrame: 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
measure: Description of the population of patients having a cardio-vascular adverse event
timeFrame: 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
measure: Cardio-vascular toxicity of ICIs.
timeFrame: 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
measure: 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
timeFrame: 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
Other outcomes:
Locations:
city: Paris
country: France
facility: AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.
Study officials:
References:
citation: 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. No abstract available.
citation: 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.
citation: 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. No abstract available.
citation: 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. doi: 10.1161/CIRCULATIONAHA.118.034497.
citation: Nguyen LS, Bretagne M, Arrondeau J, Zahr N, Ederhy S, Abbar B, Pinna B, Allenbach Y, Mira JP, Moslehi J, Rosenzwajg M, Salem JE. Reversal of immune-checkpoint inhibitor fulminant myocarditis using personalized-dose-adjusted abatacept and ruxolitinib: proof of concept. J Immunother Cancer. 2022 Apr;10(4):e004699. doi: 10.1136/jitc-2022-004699.