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RecruitingNCT04294771JOCARDITEUpdated Sep 11, 2026

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

An observational study in Myocarditis, Cardiomyopathies and Heart Diseases, sponsored by Groupe Hospitalier Pitie-Salpetriere. Recruiting at 1 site in France. Per ClinicalTrials.gov, last updated 2026-09-11.

Sponsored by Groupe Hospitalier Pitie-Salpetriere · Observational

From the registry’s dates

  • Started Jan 2019; still recruiting 7 years 10 months later.
Study type
Observational
Model
Other
Time perspective
Retrospective
Enrollment
500,000
Sex
All
01

Study 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

Read the 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

02

Conditions studied

  • Myocarditis
  • Cardiomyopathies
  • Heart Diseases
  • Cardiovascular Diseases
  • Pericarditis
  • Vasculitis

Keywords

  • Drug-induced cardiotoxicity
  • Immune Checkpoint Inhibitors
  • Anti-PD-1
  • Anti-PD-L1
  • Anti CTLA-4
03

In context

Myocarditis

174 studies on the registry are indexed under Myocarditis; 75 are open to participants now.

This study's planned enrollment of 500,000 is above the median of 208 across 120 observational studies indexed under Myocarditis.

Browse Myocarditis studies →

Lead sponsor

Groupe Hospitalier Pitie-Salpetriere is the lead sponsor of 66 studies on the registry; 4 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Patients treated with an ICI for a cancer

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

Exclusion Criteria:

  • Chronology not compatible between the drug and the toxicity
05

Study design

Observational model
Other
Time perspective
Retrospective
Enrollment
500,000 participants (estimated)
Patient registry
No

Groups and cohorts

  • 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

  • DrugICI

    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

This study also gives Pembrolizumab, Nivolumab, Ipilimumab, Durvalumab, Atezolizumab. No intervention listed here names it: that was found by reading the record.

06

What researchers measure

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

    Time frame: 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

  1. Causality assessment of reported cardiovascular events

    Time frame: 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

  2. Description of the type of cardiotoxicity depending on the category of ICIs

    Time frame: 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

  3. Description of the duration of treatment when the toxicity happens (role of cumulative dose)

    Time frame: 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

  4. Description of the drug-drug interactions associated with adverse events

    Time frame: 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

  5. Description of the pathologies (cancer) for which the incriminated drugs have been prescribed

    Time frame: 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

  6. Description of the population of patients having a cardio-vascular adverse event

    Time frame: 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

  7. Cardio-vascular toxicity of ICIs.

    Number of patients with cardiovascular adverse events with significant over-reporting ICIs

    Time frame: 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

  8. 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

    Time frame: 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

07

Study locations

1 of 1 sites recruiting
08

References and documents

Publications

  • 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. PubMed 29536852 ↗
  • 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. PubMed 30442497 ↗
  • 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. PubMed 31189043 ↗
  • 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. PubMed 31390169 ↗
  • 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. 2026 Mar 5;47(9):1050-1062. doi: 10.1093/eurheartj/ehaf315. PubMed 40569849 ↗
  • 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. PubMed 38883792 ↗
  • 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. PubMed 35383117 ↗

Individual participant data

Plan to share: No

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Jan 2019 (actual). Primary completion is estimated for Jan 2030, 132 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Mar 2, 2020
First posted
Mar 4, 2020
StartActual
Jan 1, 2019
Primary completionEst.
Jan 1, 2030
CompletionEst.
Jan 1, 2030
Last update
Sep 11, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 11, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04294771
Lead sponsor
Groupe Hospitalier Pitie-Salpetriere
Responsible party
Joe Elie Salem (Principal Investigator, Groupe Hospitalier Pitie-Salpetriere) — Principal investigator
First posted
Mar 4, 2020
Start date
Jan 1, 2019
Primary completion
Jan 1, 2030 (estimated)
Completion
Jan 1, 2030 (estimated)
Last update
Sep 11, 2026

Study contacts

Joe-Elie SALEM, MD PhD
Contact
joe-elie.salem@aphp.fr
142178531 ext. +33

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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