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

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ClinicalTrials.gov Identifier: NCT03387540
Recruitment Status : Completed
First Posted : January 2, 2018
Last Update Posted : September 26, 2019
Sponsor:
Collaborators:
Institute of Cardiometabolism and Nutrition, France
Vanderbilt University
Vanderbilt University Medical Center
Information provided by (Responsible Party):
Joe Elie Salem, Groupe Hospitalier Pitie-Salpetriere

Brief Summary:
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.

Condition or disease Intervention/treatment
Myocarditis Cardiac Complication Drug: ICI

Detailed Description:
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.

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Study Type : Observational [Patient Registry]
Actual Enrollment : 104 participants
Observational Model: Case-Only
Time Perspective: Cross-Sectional
Target Follow-Up Duration: 2 Days
Official Title: Evaluation of Reporting of Immune Checkpoint Inhibitor Associated Cardio-vascular Adverse Reactions Using International Pharmacovigilance Database
Actual Study Start Date : December 2, 2017
Actual Primary Completion Date : December 4, 2017
Actual Study Completion Date : December 31, 2017

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Myocarditis induced by Immune check point inhibitor
Case reported in the World Health Organization (WHO) of myocarditis of patient treated by ICI, with a chronology compatible with the drug toxicity
Drug: ICI
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 Outcome Measures :
  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 Outcome Measures :
  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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients treated with an ICI for a cancer
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03387540


Locations
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France
AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.
Paris, France, 75013
Sponsors and Collaborators
Groupe Hospitalier Pitie-Salpetriere
Institute of Cardiometabolism and Nutrition, France
Vanderbilt University
Vanderbilt University Medical Center

Additional Information:

Publications of Results:
Other Publications:
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Responsible Party: Joe Elie Salem, Principle investigator, Groupe Hospitalier Pitie-Salpetriere
ClinicalTrials.gov Identifier: NCT03387540     History of Changes
Other Study ID Numbers: CIC1421-17-12
First Posted: January 2, 2018    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Joe Elie Salem, Groupe Hospitalier Pitie-Salpetriere:
Anti-PD-1
Anti-PD-L1
Anti CTLA-4
Immune checkpoint inhibitors
Additional relevant MeSH terms:
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Myocarditis
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases