ATROPOS: Survival Analysis of ICI-associated Myocarditis (ATROPOS)

ATROPOS: Assessing morTality and Risk factOrs in Immune checkPoint Inhibitor-induced myotOxicities: a Survival Analysis Based on an International Registry

ATROPOS is an international, registry-based observational study of cancer patients with immune checkpoint inhibitor-associated myocarditis (ICI-M). The study evaluates whether immunosuppressive treatment strategies, including first-line glucocorticoids and subsequent second-line immunosuppressants, are associated with overall mortality, and whether these associations vary according to myocarditis severity. The target number of cases to be included is 1500 spanning from at least 160 centers, located in at least 18 countries. Analyses will adjust for clinically relevant confounders and may use time-dependent survival models where appropriate.

Study Overview

• Status: Recruiting
• Conditions: Immune Checkpoint Inhibitor-associated Myocarditis

Detailed Description

"ATROPOS (Assessing lethaliTy and Risk factOrs in immune checkPoint inhibitors-induced myOcardia survival analysis based on an international registry) is an observational, non-interventional analysis of the international REDCap registry of immune checkpoint inhibitor-associated myocarditis (ICI-M).

The study population consists of cancer patients exposed to immune checkpoint inhibitors and recorded in the registry with possible, probable, or definite ICI-M according to registry/adjudication definitions. The main objective is to evaluate associations between immunosuppressive treatment strategies and overall mortality, as a function of myocarditis severity, focusing on first-line glucocorticoids and the subsequent use of second-line immunosuppressants. The study will also assess whether these associations are modified by myocarditis severity. Secondary analyses will examine mortality at 30, 90 and 360 days, cause-specific death (e.g. myotoxicity, cancer-related) where available, and clinical risk factors related to oncology history, ICI exposure, symptoms, ECG, echocardiography, cardiac MRI, biomarkers including CK and troponin, other immune-related adverse events, heart failure, respiratory muscle failure, arrhythmias and conductive disorders, sepsis, and pharmacological treatments.

The statistical approach will include descriptive analyses and Cox proportional-hazards modelling. Time-dependent covariates will be considered for variables such as troponin, left ventricular ejection fraction, severity/grade of the myocarditis/myotoxicity, glucocorticoids and other immunosuppressants. Missing data will be described and handled through prespecified methods, with MICE and JointAI used to cross-check robustness of results. Because treatment strategies are not assigned by the protocol, all treatment-effect analyses will be interpreted as observational associations, adjusted for prespecified clinical confounders.

ATROPOS does not assign study treatment, change patient management, require extra visits, or involve a study drug/device. The central analysis dataset uses coded or pseudonymised data, with direct identifiers retained only by local sites when applicable under their own governance."

• Study Type: Observational
• Enrollment (Estimated): 1500

Contacts and Locations

• Study Contact: Name: Joe-Elie Salem, MD-PhD; Phone Number: 0033142178531; Email: joe-elie.salem@aphp.fr

Study Locations

• France
  • Paris, France
    • Recruiting
    • Hopital Pitie-Salpetriere / CIC-2503
    • Contact: Joe-Elie Salem, MD-PhD; Phone Number: 0033142178531; Email: joe-elie.salem@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Cancer patients exposed to immune checkpoint inhibitors and recorded in a REDCap international ICI-Myocarditis registry, including cases with clinical, biomarker, ECG, imaging, treatment, complication and mortality/outcome data sufficient for the planned survival analyses.

Description

Inclusion Criteria:

cancer patients exposed to at least one immune checkpoint inhibitor possible, probable or definite immune checkpoint inhibitor-associated myocarditis recorded in the international registry according to registry/adjudication definitions available index-date/presentation information available mortality follow-up.

Exclusion Criteria:

duplicate records not enough data to classify as myocarditis record/patient withdrawn from research use unresolved data-quality issues preventing inclusion in the final SAP-defined analysis set.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality at 90 days after ICI-M presentation/index date	Death from any cause within 90 days of ICI-M presentation/index date, analysed in relation to immunosuppressive treatment strategy and adjusted for prespecified confounders. Treatment and selected clinical variables may be handled as time-dependent covariates.	90 days from ICI-M presentation/index date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality at 30 days and 360 days after ICI-M presentation/index date	Mortality (with cause-specific approach) at early and longer follow-up horizons; compare overall and sensitivity models across imputation approaches, handling of competitive risks and time-dependent-covariate strategies.	30 days and 360 days from ICI-M presentation/index date
Modification of treatment-mortality association by myocarditis severity	Interaction/sensitivity analyses evaluating whether myocarditis severity modifies the association between glucocorticoid or not and second-line immunosuppressive strategies and mortality outcomes.	Up to 360 days from ICI-M presentation/index date

Collaborators and Investigators

• Sponsor: Groupe Hospitalier Pitie-Salpetriere
• Collaborators: Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 2, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: mortality; myocarditis; REDCap; immune checkpoint inhibitors; myotoxicity
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Cardiovascular Diseases; Muscular Diseases; Wounds and Injuries; Pathologic Processes; Heart Diseases; Neuromuscular Diseases; Chemically-Induced Disorders; Cardiomyopathies; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Pathological Conditions, Signs and Symptoms; Myotoxicity; Myocarditis
• Other Study ID Numbers: CIC2503-26-06 (Registry Identifier: REDCap International ICI-myocarditis registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No