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

Myocarditis Clinical Trial

— RAFALE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03387540
• Other study ID #: CIC1421-17-12
• Status: Completed
• Start date: December 2, 2017
• Est. completion date: December 31, 2017

Study information

• Verified date: September 2019
• Source: Groupe Hospitalier Pitie-Salpetriere
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: December 31, 2017
• Est. primary completion date: December 4, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Complication
• Myocarditis

Intervention

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).

Locations

Country	Name	City	State
France	AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.	Paris

Sponsors (4)

Lead Sponsor	Collaborator
Groupe Hospitalier Pitie-Salpetriere	Institute of Cardiometabolism and Nutrition, France, Vanderbilt University, Vanderbilt University Medical Center

Country where clinical trial is conducted

France, 

References & Publications (4)

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

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. — View Citation

Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Reporting of immune checkpoint inhibitor-associated myocarditis - Authors' reply. Lancet. 2018 Aug 4;392(10145):384-385. doi: 10.1016/S0140-6736(18)31556-3. — View Citation

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, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardio-vascular toxicity of ICIs.	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).	Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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