Apixaban for the prevention of venous thromboembolism in high-risk ambulatory cancer patients receiving chemotherapy: Rational and design of the AVERT trial

Abstract

Patients with active cancer have a heightened risk of venous thromboembolism (VTE). This risk is further increased by the initiation of chemotherapy. Although previous studies have suggested that the use of parenteral thromboprophylaxis in all ambulatory cancer patients receiving chemotherapy significantly decreases the rate of VTE, current clinical practice guidelines do not recommend routine use of thromboprophylaxis in this patient population. A major criticism of these studies has been the inclusion of patients at lower risk for VTE, which may have diluted the potential beneficial effect of the parenteral thromboprophylaxis. It is therefore imperative to appropriately risk stratify ambulatory cancer patients using a validated scoring system (e.g. Khorana risk score) in order to identify those most likely to benefit from thromboprophylaxis. Direct oral anticoagulants, such as apixaban, may offer a convenient and safe option for thromboprophylaxis. As such, AVERT will randomize 574 ambulatory cancer patients receiving chemotherapy who are at high-risk for VTE (as defined by a Khorana score of ≥2) to Apixaban 2.5 mg BID versus placebo. The primary study outcome will be the first episode of objectively documented symptomatic or incidental VTE (deep vein thrombosis and/or pulmonary embolism) within the first 6 months (180 days ± 3) following initiation of the blinded study drug for both intervention and placebo groups. The secondary safety outcomes include major bleeding, clinically relevant non-major bleeding, and overall survival rates. This study will hopefully offer evidence regarding the benefit of apixaban in ambulatory patients at high risk for VTE receiving chemotherapy.

Keywords: Haemorrhage; Neoplasm; Thromboprophylaxis; Venous thromboembolism; Venous thrombosis.