Apixaban thromboprophylaxis to prevent venous thromboembolism in ambulatory lung cancer patients undergoing systemic anticancer treatment.

Research question: Does thromboprophylaxis with apixaban reduce venous thromboembolism in ambulatory patients with primary lung cancer undergoing systemic anticancer therapy. Background: Venous thromboembolism (VTE) is common in lung cancer and results in worse quality of life, increased healthcare costs, increased morbidity, and mortality. VTE is also increased in lung cancer patients undergoing systemic anticancer therapy (SACT). VTE can be reduced using anticoagulation as thromboprophylaxis, but this is not the current standard of care for outpatients having SACT. The subcutaneous anticoagulant low molecular weight heparin can reduce VTE in lung cancer but can be inconvenient to take. Apixaban is a type of direct oral anticoagulant (DOAC) taken in tablet form and not requiring regular blood monitoring, which have a good safety profile and are licensed for other medical conditions. Whilst anticoagulants have been used for thromboprophylaxis in patients with cancer, the role of DOACs in ambulatory lung cancer patients is unanswered by the existing literature. Aims and objectives: Primary outcome The primary outcome is to determine if objectively confirmed VTE (composite) is reduced by treatment with 6 months of apixaban 2.5mg BD in ambulatory lung cancer patients commencing SACT alone or as multi-modal therapy. Secondary outcomes These include investigating the effect of apixaban thromboprophylaxis on composite bleeding events, individual components of the composite primary efficacy outcome, VTE-related death, vascular death, other rates of thrombosis (arterial thromboembolism, visceral thromboembolism, stroke, myocardial infarction), net clinical benefit (combining efficacy and safety endpoints) and quality of life. We will also assess medication adherence, acceptability, cost effectiveness and include lung cancer core outcome sets. Other secondary outcomes include individual components of the primary efficacy outcome, VTE-related death (and its components), vascular death, other thrombosis rates (arterial thromboembolism, visceral thromboembolism, stroke, myocardial infarction), and net clinical benefit Methods: THROMBO-STOP is a multicentre, double blind, placebo-controlled, parallel group, two arm, phase 3 randomised clinical trial testing the efficacy of Apixaban to reduce VTE in ambulatory lung cancer patients undergoing SACT. There will be a 12-month internal pilot, process evaluation, acceptability study and economic evaluation. For this superiority trial, 1456 patients (728 per group) are required to have a 90% power of detecting, as significant with an alpha of 0.05 (two-sided), a decrease in the rate of VTE from 8.6% in the control group (placebo) to 4% in the intervention group (apixaban), assuming a 20% drop-out rate. The planned recruitment of 1456 patients over a 36-month window would involve 34 sites. Timelines for delivery: THROMBO-STOP patients will be recruited over a 36-month period which includes a 12-month internal pilot. The overall study time will be 60 months accounting for trial set up and analysis. Anticipated impact and dissemination: Dissemination will occur through conferences and publications, as well as through the trial PPI group and a regular newsletter. Impact is anticipated through changes in National guidelines on lung cancer and VTE.