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

• Sponsor: Groupe Hospitalier Pitie-Salpetriere (Other)
• Overall Status: Completed
• CT.gov ID: NCT03387540
• Collaborator: Institute of Cardiometabolism and Nutrition, France (Other), Vanderbilt University (Other), Vanderbilt University Medical Center (Other)
• Enrollment: 104
• Location: 1
• Actual Duration (Days): 29
• Patients Per Site Per Month: 109.2

Study Details

Study Description

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	Phase
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.

Study Design

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

Arms and Interventions

Arm	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).

Outcome Measures

Primary Outcome Measures

1. Cardio-vascular toxicity of ICIs. [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 [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 [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) [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 [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 [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 [Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Dressler D, Potter H. Molecular mechanisms in genetic recombination. Annu Rev Biochem. 1982;51:727-61. Review.

• Responsible Party: Joe Elie Salem, Principle investigator, Groupe Hospitalier Pitie-Salpetriere
• ClinicalTrials.gov Identifier: NCT03387540
• Other Study ID Numbers: CIC1421-17-12
• First Posted: Jan 2, 2018
• Last Update Posted: Sep 26, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• 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, Principle investigator, Groupe Hospitalier Pitie-Salpetriere: Anti-PD-1; Anti-PD-L1; Anti CTLA-4; Immune checkpoint inhibitors
• Additional relevant MeSH terms: Myocarditis

Study Results

No Results Posted as of Sep 26, 2019