Venous thromboembolism (VTE) is a disorder that includes deep vein thrombosis and pulmonary embolism. A deep vein thrombosis occurs when a blood clot forms in a deep vein, usually in the lower leg, thigh, or pelvis. A pulmonary embolism occurs when a clot breaks loose and travels through the bloodstream to the lungs. The risk of developing VTE is highest after major surgery or a major injury, or when you have heart failure, cancer, or a heart attack.
Anticoagulants, or blood thinners, keep blood clots from getting larger and stop the formation of further clots, preventing strokes or heart failure. Possible side effects include bleeding, especially if you are taking other medicines that also thin your blood, such as aspirin. Edoxaban is an oral anticoagulant approved in 2015 for patients with VTE.
A European clinical study (ETNA-VTE) is ongoing to understand the risks and benefits of using edoxaban in real-world clinical settings and to gain insight into efficacy (i.e. recurrence of blood clots) and safety (i.e. bleeding events and adverse reactions to the medication) in patients affected by VTE. The study also measures the risk of death and of being hospitalised for causes potentially related to edoxaban.
The main objective of this study is to replicate the analyses planned in the ETNA-VTE study using secondary health data of patients who has been prescribed edoxaban collected in daily practice in the UK and compare the results.
Daiichi-Sankyo is currently undertaking a non-interventional post-approval safety study (ETNA study - EU-PAS register numbers EUPAS15504), in order to understand the risks and benefits of edoxaban in the real-world, as part of the Risk Management Plan of edoxaban. The ETNA-VTE study aims to gain insight into the safety of edoxaban in non-preselected patients with VTE treated with edoxaban.
In this non-interventional retrospective study we aim to evaluate the safety and efficacy of edoxaban in patients diagnosed with venous thromboembolism (VTE) between 2015 and 2019 in the United Kingdom, using the Clinical Practice Research Datalink (CPRD) both Aurum and GOLD with linkage to Hospital Episode Statistics (HES) databases. This study will provide supporting evidence to the ETNA-VTE study and highlight specific information for UK.
We will use Hospital Episode Statistics (HES) data to identify clinical events of interest, hospitalisations, all causes and related to specific conditions. Linkage to Office of National Statistic (ONS) will allow the determination of mortality rates (all-causes, CV- or VTE- specific).
The primary analysis will estimate the overall diagnosed VTE recurrence rate and the frequency of occurrence of safety events, including major bleeding events, non-major bleeding drug-related adverse events, mortality, in patients with VTE treated with edoxaban during an overall observational period of 18 months.
Secondary analysis will assess the impact of edoxaban level of exposure on endpoints such as: stroke (ischaemic and haemorrhagic), systemic embolic events (SEE), hospitalizations related to CV condition including VTE-related hospitalisation, Post-thrombotic syndrome (PTS) and malignancy.
Comparisons of various subgroups and covariates will be done via adjusted Cox proportional hazard regression models presenting hazard ratios and corresponding 95% confidence intervals.
The primary outcomes will be:
Safety measures:
- Bleedings:
- Major bleeding (see Section N. Exposures, Outcomes and Covariates for details)
- Non-major bleeding (see Section N. Exposures, Outcomes and Covariates for details)
- Adverse drug reactions (see Section N. Exposures, Outcomes and Covariates for details)
- Mortality: All-cause mortality, VTE-related, CV mortality
Effectiveness measures: VTE recurrence
The secondary outcomes will be:
Efficacy measures
- recurrence rate of VTE for patients on edoxaban
- recurrence rate of VTE for patients who permanently discontinued edoxaban
Safety measures
- Stroke (ischaemic and haemorrhagic)
- Systemic Embolic Events (SEE)
- Hospitalizations related to cardiovascular (CV) condition (including VTE related hospitalisation)
- Post Thrombotic Syndrome (PTS)
FLORENT Guelfucci - Chief Investigator - Syneos Health Commercial France SARL
FLORENT Guelfucci - Corresponding Applicant - Syneos Health Commercial France SARL
Brian Buysse - Collaborator - Syneos Health
Florence Bianic - Collaborator - Syneos Health Consulting Inc (formerly inVentiv)
Petra Laeis - Collaborator - Daiichi Sankyo Europe GmbH (Germany)
Stefano Perni - Collaborator - Syneos Health
HES Accident and Emergency;HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation