Clinical trial NCT03387540: Evaluation of Reporting of Immune Checkpoint Inhibitor Associated Cardio-vascular Adverse Reactions
Official title: Evaluation of Reporting of Immune Checkpoint Inhibitor Associated Cardio-vascular Adverse Reactions Using International Pharmacovigilance Database
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myocarditis
Cardiac Complication
Keywords: Anti-PD-1
Anti-PD-L1
Anti CTLA-4
Immune checkpoint inhibitors
Lead sponsor: Groupe Hospitalier Pitie-Salpetriere
Sponsor class: OTHER
Collaborators: name: Institute of Cardiometabolism and Nutrition, France
name: Vanderbilt University
name: Vanderbilt University Medical Center
First posted: 2018-01-02
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients treated with an ICI for a cancer

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.

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.

Eligibility 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

Primary outcomes:
measure: Cardio-vascular toxicity of ICIs.
timeFrame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Secondary outcomes:
measure: Causality assessment of reported cardiovascular events according to the WHO system
timeFrame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
measure: Description of the type of cardiotoxicity depending on the category of ICIs
timeFrame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
measure: Description of the duration of treatment when the toxicity happens (role of cumulative dose)
timeFrame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
measure: Description of the drug-drug interactions associated with adverse events
timeFrame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
measure: Description of the pathologies (cancer) for which the incriminated drugs have been prescribed
timeFrame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
measure: Description of the population of patients having a cardio-vascular adverse event
timeFrame: Case reported in the World Health Organization (WHO) database of individual safety case reports to 12/31/2017
Other outcomes:
Locations:
city: Paris
country: France
facility: AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.
Study officials:
References:
citation: Dressler D, Potter H. Molecular mechanisms in genetic recombination. Annu Rev Biochem. 1982;51:727-61. doi: 10.1146/annurev.bi.51.070182.003455. No abstract available.
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. No abstract available.
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. No abstract available.
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, pharmacovigilance study. Lancet Oncol. 2018 Dec;19(12):1579-1589. doi: 10.1016/S1470-2045(18)30608-9. Epub 2018 Nov 12.