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

NCT04294771 | Unknown FDA Drug

• 1 other identifier: CIC1421-20-03
• Study Type: observational
• Target: 500,000
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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

Study Arms (2)

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

Non case

Non-case will be patients exposed to ICI without cardiovascular toxicities

Drug: ICI

Interventions

ICI DRUG

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)

Also known as: Immune checkpoint inhibitors

Myocarditis and other cardiovascular toxicities ICI-related; Non case

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients treated with an ICI for a cancer

You may qualify if:

• 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)

You may not qualify if:

• Chronology not compatible between the drug and the toxicity

Sponsors & Collaborators

• Groupe Hospitalier Pitie-Salpetriere: lead

Study Sites (1)

AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.

Paris, 75013, France

RECRUITING

Related Publications (7)

• 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.

  PMID: 29536852 BACKGROUND

• 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.

  PMID: 30442497 BACKGROUND

• 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.

  PMID: 31189043 BACKGROUND

• 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.

  PMID: 31390169 BACKGROUND

• Power JR, Dolladille C, Ozbay B, Procureur A, Ederhy S, Palaskas NL, Lehmann LH, Cautela J, Courand PY, Hayek SS, Zhu H, Zaha VG, Cheng RK, Alexandre J, Roubille F, Baldassarre LA, Chen YC, Baik AH, Laufer-Perl M, Tamura Y, Asnani A, Francis S, Gaughan EM, Rainer PP, Bailly G, Flint D, Arangalage D, Cariou E, Florido R, Narezkina A, Liu Y, Sandhu S, Leong D, Issa N, Piriou N, Heinzerling L, Peretto G, Crusz SM, Akhter N, Levenson JE, Turker I, Eslami A, Fenioux C, Moliner P, Obeid M, Chan WT, Ewer SM, Kassaian SE, Johnson DB, Nohria A, Ben Zadok OI, Moslehi JJ, Salem JE; International ICI-Myocarditis Registry. Immune checkpoint inhibitor-associated myocarditis: a novel risk score. Eur Heart J. 2025 Jun 18:ehaf315. doi: 10.1093/eurheartj/ehaf315. Online ahead of print.

  PMID: 40569849 DERIVED

• Power JR, Dolladille C, Ozbay B, Procureur AM, Ederhy S, Palaskas NL, Lehmann LH, Cautela J, Courand PY, Hayek SS, Zhu H, Zaha VG, Cheng RK, Alexandre J, Roubille F, Baldassarre LA, Chen YC, Baik AH, Laufer-Perl M, Tamura Y, Asnani A, Francis S, Gaughan EM, Rainer PP, Bailly G, Flint D, Arangalage D, Cariou E, Florido R, Narezkina A, Liu Y, Sandhu S, Leong D, Issa N, Piriou N, Heinzerling L, Peretto G, Crusz SM, Akhter N, Levenson JE, Turker I, Eslami A, Fenioux C, Moliner P, Obeid M, Chan WT, Ewer SM, Kassaian SE; International ICI-Myocarditis Registry; Johnson DB, Nohria A, Zadok OIB, Moslehi JJ, Salem JE. Predictors and Risk Score for Immune Checkpoint-Inhibitor-Associated Myocarditis Severity. medRxiv [Preprint]. 2024 Jun 3:2024.06.02.24308336. doi: 10.1101/2024.06.02.24308336.

  PMID: 38883792 DERIVED

• 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.

  PMID: 35383117 DERIVED

MeSH Terms

Conditions

Myocarditis; Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Pericarditis; Vasculitis

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Vascular Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Joe-Elie SALEM, MD PhD

CONTACT

142178531; joe-elie.salem@aphp.fr

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 4, 2020
• Study Start: January 1, 2019
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: September 15, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)