Protocol No: ECCT/14/12/01 Date of Protocol: 18-02-2014

Study Title:

XALIA LEA- Xarelto® for Long-term and
Initial Anticoagulation in Venous
Thromboembolism (VTE) in Latin America,
EMEA and Asia

Study Objectives:
Laymans Summary:
Abstract of Study:

Acute venous thromboembolism (i.e. deep-vein thrombosis [DVT] or pulmonary
embolism [PE]) is a common disorder with an annual incidence of approximately 1
or 2 cases per 1000 persons in the general population and is the third most common
cause of vascular death after myocardial infarction and stroke. The current standard
treatment for DVT is overlapping parenteral anticoagulation (e.g. LMWH) and a
vitamin K antagonist (e.g. warfarin). Parenteral anticoagulation needs to be
continued for 5 to 7 days, at least until an INR of 2.0 has been obtained, followed by
a minimum of 3 months of treatment with the vitamin K antagonist. Treatment with
vitamin K antagonists requires frequent monitoring of the international normalized
ratio (INR), and multiple interactions of vitamin K antagonists with foods and other
drugs have been reported. The duration of treatment is determined by individual risk
factors of the patient.
Rivaroxaban is a direct factor Xa inhibitor, and has been approved first in the
prevention of venous thromboembolism after elective hip and knee replacement
surgery. It does not require routine laboratory monitoring and has no food
interactions and only a few drug interactions compared to standard of care.
As part of the development program, the EINSTEIN clinical trial program was
designed to evaluate the use of rivaroxaban for the acute treatment and secondary
prevention of DVT (EINSTEIN-DVT) and PE (EINSTEIN-PE) and in long-term
secondary prevention of recurrent DVT and PE (EINSTEIN-EXT). A unique aspect
of the EINSTEIN-DVT and PE studies is the use of rivaroxaban as a single agent
(single drug approach) in contrast to the use of intravenous anticoagulants and
The EINSTEIN-DVT study demonstrated that rivaroxaban is at least as effective as
the current standard therapy with similar safety, in the treatment and secondary
prevention of DVT. The EINSTEIN PE study demonstrated non-inferior efficacy of
rivaroxaban compared to standard of care with similar rates of major and clinically
relevant non-major bleeding. EINSTEIN PE further demonstrated a significant
reduction of major bleeding events in patients treated with rivaroxaban compared to
standard of care. EINSTEIN-EXT demonstrated that continued treatment with
rivaroxaban after 6 or 12 months initial treatment is superior in preventing
recurrences, as compared with placebo, and has an acceptable risk of bleeding.
At the time of writing, rivaroxaban is approved by the EMA, the FDA, Singapore,
Malaysia, Indonesia, Philippines, Taiwan, Korea and Mexico, Brazil, Argentina,
Chile, Colombia, Peru, Ecuador, Uruguay, and several other countries in Latin
America as well as in the EMEA region Saudi Arabia, Egypt, Middle Africa, UAE,
Kuwait, Qatar, Turkey, Jordan, Lebanon, Russia, Kazakhstan and Algeria for the
treatment of acute DVT, PE and recurrent VTE following DVT or PE in adults. The
approved dose is 15mg bid for the first 21 days followed by 20mg od for the
continuing treatment period. Further dosing information are listed in detail in the
Summary of Product Characteristics (SmPC). In the European Union and other
countries, rivaroxaban is the first agent that allows treatment of thrombotic events
with a single drug approach. Treatment with rivaroxaban can be already initiated at
diagnosis and does not require intravenous/subcutaneous heparin or VKA anymore.
If the decision is made to switch treatment from rivaroxaban to current standard of
care, adequate anticoagulation has to be ensured. In patients converting from rivaroxaban to VKA, VKA should be given concurrently until the INR is ≥2.0.
Patients converting from rivaroxaban to parenteral anticoagulation should receive
the parenteral anticoagulant at the time originally scheduled for the intake of
Bayer conducts the XALIA LEA study to yield complementary post-authorization
information in rivaroxaban or standard therapy patients under real-life conditions.