Evaluation of Reporting of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor Inhibitors Associated Cardiovascular Adverse reactioN. (VEGAN)

Evaluation of Reporting of VEGF Inhibitors Associated Cardiovasclular Adverse reactioNs Using International Pharmacovigilance Database.

Antiangiogenics (AAs) which are vascular endothelial growth factor (VEGF) or VEGF receptor (VEGFR) inhibitors might have high grade adverse events (AEs) on the cardio-vascular system. This study investigates reports of cardio-vascular toxicity with treatment including VEGF and VEGFR inhibitors using the World Health Organization (WHO) database VigiBase.

Study Overview

• Status: Completed
• Conditions: Vascular Diseases; Cardiac Complication
• Intervention / Treatment: Drug: Cardiac complication induced by VEGF/VEGFR inhibitor

Detailed Description

AAs have dramatically improved clinical outcomes in multiple cancer types and are increasingly being tested in earlier disease settings and used in combination. However, AEs 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 AAs.

• Study Type: Observational
• Enrollment (Actual): 150000

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients treated with an AA for a cancer

Description

Inclusion Criteria:

• Case reported in the World Health Organization (WHO) database of individual safety case reports to 01/01/2018
• Adverse event reported were including the MedDRA terms: Cardiac disorders (SOC), Vascular disorders (SOC), Sudden death (PT)
• Patients treated with antiangiogenics included in the following list:

Exclusion Criteria:

• Chronology not compatible between the drug and the toxicity

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardio-vascular toxicity of AAs	Identification and report of the cardio-vascular toxicity of AAs. The research includes the report with MedDRA terms: SOC Cardiac Disorders, SOC Vascular Disorders, Sudden death (PT). Drugs investigated are: sorafenib, sunitinib, pazopanib, vandetanib, axitinib, regorafenib, nintedanib, lenvatinib, ceritinib, bevacizumab, ramucirumab, aflibercept.	Case reported in the World Health Organization (WHO) database of individual safety case reports to 01/01/2018

Secondary Outcome Measures

Outcome Measure	Time Frame
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 01/01/2018
Description of the type of cardiotoxicity depending on the category of AAs	Case reported in the World Health Organization (WHO) database of individual safety case reports to 01/01/2018
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 01/01/2018
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 01/01/2018
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 01/01/2018
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 01/01/2018

Collaborators and Investigators

• Sponsor: Groupe Hospitalier Pitie-Salpetriere

Publications and helpful links

General Publications

• Alexandre J, Moslehi JJ, Bersell KR, Funck-Brentano C, Roden DM, Salem JE. Anticancer drug-induced cardiac rhythm disorders: Current knowledge and basic underlying mechanisms. Pharmacol Ther. 2018 Sep;189:89-103. doi: 10.1016/j.pharmthera.2018.04.009. Epub 2018 Apr 24.
• Gougis P, Wassermann J, Spano JP, Keynan N, Funck-Brentano C, Salem JE. Clinical pharmacology of anti-angiogenic drugs in oncology. Crit Rev Oncol Hematol. 2017 Nov;119:75-93. doi: 10.1016/j.critrevonc.2017.08.010. Epub 2017 Sep 1.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2018
• Primary Completion (ACTUAL): January 15, 2018
• Study Completion (ACTUAL): January 31, 2018

Study Registration Dates

• First Submitted: January 22, 2018
• First Submitted That Met QC Criteria: January 22, 2018
• First Posted (ACTUAL): January 29, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 26, 2019
• Last Update Submitted That Met QC Criteria: September 24, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: VEGF; angiogenesis; VEGFR; antiangiogenics
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases
• Other Study ID Numbers: CIC1421-18-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• 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