Patients with acute
venous thromboembolism (VTE) in the setting of transient provoking factors are typically treated with short-term anticoagulation. However, the risk of recurrence may be increased in the presence of enduring risk factors. In such patients, the optimal
duration of treatment remains uncertain. HI-PRO is a single-center, double-blind randomized trial. Patients with
deep vein thrombosis (DVT) or
pulmonary embolism (PE) following a major provoking factor, including major surgery or major
trauma, who completed at least 3 months of standard-dose therapeutic anticoagulation and have at least one enduring risk factor (such as
obesity or
heart failure) will be considered for inclusion. Patients will be randomized to
apixaban 2.5 mg twice daily or placebo for 12 months. The primary efficacy outcome will be symptomatic recurrent VTE-a composite of DVT and/or PE at 12 months after randomization. Secondary efficacy outcomes include a composite of death due to cardiovascular causes, nonfatal
myocardial infarction,
stroke or systemic
embolism, major adverse limb events, or coronary or peripheral
ischemia requiring revascularization at 12 months, and individual components of these outcomes. The primary safety outcome is major
bleeding according to the International Society on
Thrombosis and Haemostasis definition. The study plans to enroll 600 patients (300 per arm) to have 80% power for detecting a 75% relative risk reduction in the primary outcome. Active recruitment began in March 2021. HI-PRO will provide clinically meaningful data on whether patients with provoked VTE and enduring risk factors have fewer adverse clinical outcomes if prescribed low-intensity extended-duration anticoagulation.