Treatment with Oral Treprostinil Delays Time to Clinical Worsening in Patients with Pulmonary Arterial Hypertension - Results from FREEDOM-EV

Abstract

Purpose Oral treprostinil (TRE) has been shown to improve exercise capacity in patients with pulmonary arterial hypertension (PAH), but its effect on clinical outcomes was unknown. Methods In this global, event-driven study, eligible participants taking one approved PAH medication were randomized to TRE or placebo (PBO). Dosing was individualized and titrated from 0.125 mg three times daily (TID) up to 12 mg TID. Primary objective was to determine the effect of TRE on time to first adjudicated clinical worsening (CW) event: death, hospitalization due to worsening of PAH, initiation of inhaled/infused prostacyclin, disease progression (≥ 15% decrease in six minute walk distance [6MWD] and increase in functional class [FC] or worsening heart failure), or unsatisfactory long-term clinical response. Results 690 participants were randomized (346 TRE, 344 PBO). They were predominantly female and Conclusion In participants taking one oral PAH medication, early, sequential combination therapy with TRE significantly delayed disease progression compared to PBO. Functional and symptomatic improvements at W24-48 support the primary endpoint and were greatest for those achieving ≥3 mg TID at W24.