Study OverviewFREEDOM-EV TRIAL—designed with a composite primary endpoint to assess the effect of Orenitram on time to first clinical worsening event1,2
FREEDOM-EV was an international, multicenter, randomized, double-blind, placebo-controlled, event-driven study1,2

- Patients received Orenitram or placebo starting at 0.125 mg TID and titrated to a maximum dose of 12 mg TID1
- Randomization was stratified by type of background therapy and baseline 6MWD2
Primary Endpoint
Clinical Assessments Summary
Time to First Adjudicated Clinical Worsening Event2:
Selected Secondary Endpoints
Change from baseline measured at week 242:
- Exercise capacity as assessed by 6MWD
- Right ventricle dysfunction as indicated by NT-proBNP
- Symptom improvement as indicated by WHO FC
Vital Status Substudy
- Patients who participated in FREEDOM-EV and agreed to be followed were a part of the vital status substudy2‡
- Decrease in 6MWD at week 24 and beyond, and sustained WHO FC III/IV symptoms for ≥24 weeks, consecutively.2
- Defined as a ≥15% decrease in 6MWD and increase in WHO FC, or a ≥15% decrease in 6MWD and appearance or worsening of symptoms of right heart failure.2
- The initial data collection plan stopped following participants 30 days after discontinuing randomized treatment unless they consented to participate in an open-label follow-up study. An amended protocol later included a vital status substudy; vital status was assessed every 6 months for consenting participants until closure of the randomized study in October 2018.2
The FREEDOM-EV study population was relatively young and recently diagnosed, with the majority of patients at FC II1,2

- Patients in FREEDOM-EV included 3% FC I, 63% FC II, 34% FC III, and 0.1% FC IV.2
The majority of patients had idiopathic or heritable PAH (63%)1,2
- 26% had PAH associated with connective tissue disease
- 7% had PAH associated with a congenital heart defect
- 1% had PAH associated with HIV infection
- 3% had PAH from other causes