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NCT Number: NCT03387540

Evaluation of Reporting of Immune Checkpoint Inhibitor Associated Cardio-vascular Adverse Reactions

Immune checkpoint inhibitors (ICIs) might have high grade immune-related adverse events (irAEs) on the cardio-vascular system. This study investigates reports of cardio-vascular toxicity with treatment including anti-PD1, Anti-PDL-1, and Anti CTLA4 classes using the World Health Organization (WHO) database VigiBase.

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Key information

Conditions

Myocarditis Cardiac Complication Cardiomyopathies Cardiovascular Diseases Heart Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

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

Paris, 75013, France

About this study

ICIs have dramatically improved clinical outcomes in multiple cancer types and are increasingly being tested in earlier disease settings and used in combination. However, irAEs can occur. Here the investigators use VigiBase (http://www.vigiaccess.org/), the World Health Organization (WHO) database of individual safety case reports, to identify cases of cardiovascular adverse drug reaction following treatment with ICIs.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
  • 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).

Exclusion criteria

  • Chronology not compatible between the drug and the toxicity

Treatment and study plan

ICI

Drug

Immune checkpoint inhibitor targeting either PD-1, PD-L1 or CTLA-4, and included in the following list (ATC classification): Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).

Primary outcomes

  1. Cardio-vascular toxicity of ICIs.

    Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

    Identification and report of the cardio-vascular toxicity of ICIs. The research includes the report with MedDRA terms: SOC Cardiac Disorders, SOC Vascular Disorders, Sudden death (PT), Cardiac and vascular investigations (excl enzyme tests) (HLGT), Skeletal and cardiac muscle analyses (HLT). Drugs investigated are ICIs: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).

Secondary outcomes

  1. Causality assessment of reported cardiovascular events according to the WHO system

    Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

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

    Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

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

    Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

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

    Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

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

    Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

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

    Time frame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017

Sponsors and collaborators

Lead sponsor

Groupe Hospitalier Pitie-Salpetriere

Other

Collaborators

  • Institute of Cardiometabolism and Nutrition, France
  • Vanderbilt University
  • Vanderbilt University Medical Center

Registry information

Official study title

Evaluation of Reporting of Immune Checkpoint Inhibitor Associated Cardio-vascular Adverse Reactions Using International Pharmacovigilance Database

Acronym: RAFALE

Important dates

Study start
2017
Primary completion
2017
Study completion
2017
First posted
Jan 2, 2018
Registry last updated
Sep 26, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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