REduced Dose Versus Full-dose of Direct Oral Anticoagulant After uNprOvoked Venous thromboEmbolism.
Status:
Recruiting
Trial end date:
2022-11-02
Target enrollment:
Participant gender:
Summary
Patients with unprovoked venous thromboembolism (VTE) or VTE associated with persistent risk
factors have a high risk of recurrence after stopping anticoagulation. In these patients,
international guidelines recommend indefinite anticoagulation. However, prolonged use of
warfarin or DOAC at therapeutic dose is associated with a significant risk of bleeding.
Consequently, it has been hypothesized that extended anticoagulation at lower dosage might be
as effective as and safer than full dose of anticoagulation. However, low-dose warfarin (INR
1.5-2) was less effective and not safer than conventional dose warfarin (INR 2-3).
Low dose of DOAC has the potential to validate this hypothesis. In a first randomized trial
comparing full-dose or low-dose apixaban with a placebo during an additional one year of
anticoagulation in patients where physicians were uncertain for prolonging anticoagulation
("Amplify-extension trial"), low-dose apixaban was more effective than placebo without any
major concern regarding safety and possibly as effective as and safer than full-dose
apixaban; in a second randomized trial comparing full-dose or low-dose rivaroxaban with
aspirin, during an additional one year of anticoagulation in patients where physicians were
uncertain for prolonging anticoagulation ("Einstein-Choice trial"), low-dose rivaroxaban was
more effective than aspirin without any major concern regarding safety and possibly as
effective as and safer than full-dose rivaroxaban. However, these two studies were not
designed and powered to demonstrate non-inferiority on efficacy and superiority on safety of
a reduced dose of DOAC versus a full dose DOAC and the selected population did not have
strong indications for indefinite anticoagulation. Thus, there is currently no evidence to
recommend a reduced dose rather than a full dose of DOAC for extended therapy in patients at
high risk of recurrent VTE. Consequently, a randomized trial comparing low-dose DOAC with
full-dose DOAC therapy in patients at high risk of recurrent VTE is needed and justified.
Main hypothesis:
After VTE at high risk of recurrence initially treated during 6 (-15 days) to 24 (+ 3 months)
uninterrupted months, a reduced dose of DOAC will be non-inferior to a full dose of DOAC in
terms of recurrent VTE during extended anticoagulation phase.