Trial reportAdvances in therapy2024
Oral Treprostinil is Associated with Improved Survival in FREEDOM-EV and its Open-Label Extension.
Trial report in Advances in therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01560637 (Open-Label Extension Study of UT-15C in Subjects With Pulmonary Arterial Hypertension- A Long-Term Follow-Up to Protocol TDE-PH-310), which is not on this map. Cited by 5 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Open-Label Extension Study of UT-15C in Subjects With Pulmonary Arterial Hypertension- A Long-Term Follow-Up to Protocol TDE-PH-310
Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.
- Comparative efficacy and safety of prostacyclin therapies for pulmonary arterial hypertension: a systematic review and network meta-analysis.Frontiers in medicine · 2025Pooled it
- Transitioning From Oral to Intravenous Treprostinil in Pulmonary Arterial Hypertension: A Case Report.Clinical case reports · 2026Article
- A long-term follow-up study of sotatercept for treatment of pulmonary arterial hypertension: interim results of SOTERIA.The European respiratory journal · 2025Article
- Comparative Analysis of Survival in Pulmonary Arterial Hypertension for Patients Treated with Selexipag in Clinical Practice (EXPOSURE Study).Drugs - real world outcomes · 2025Article
- The Importance of Dose Escalation in the Treatment of Pulmonary Arterial Hypertension with Treprostinil.Biomedicines · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 17 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionIn the event-driven FREEDOM-EV trial, oral treprostinil delayed clinical worsening in patients with pulmonary arterial hypertension (PAH). Open-label extension studies offer additional data about tolerability, efficacy, and survival, especially for those initially assigned placebo. The aim of the current study was to determine if oral treprostinil changed survival when considering the parent and extension study, if treprostinil provides functional benefits for participants initially assigned to placebo, and if the benefits observed for those treated with treprostinil were durable.
methodsBoth active and placebo participants from FREEDOM-EV could enroll in the FREEDOM-EV open-label extension (OLE) study after experiencing an investigator-assessed clinical worsening event or after parent study closure. All participants in the OLE were offered open-label oral treprostinil. Previously assigned placebo participants titrated to maximally tolerated doses; previously assigned treprostinil participants continued dose titration. We repeated assessments including functional class and 6-min walk distance (6MWD) at 12-week intervals and measured N-terminal pro-brain natriuretic peptide (NT-proBNP) at week 48. Survival was estimated by Kaplan-Meier analysis, and we estimated hazard ratio (HR) using Cox proportional hazards.
resultsOf 690 FREEDOM-EV participants, 470 enrolled in the OLE; vital status was available for 89% of initial Freedom-EV participants. When considering the combined parent and open-label data, initial assignment to oral treprostinil reduced mortality (HR 0.64, 95% confidence interval 0.46-0.91, p = 0.013); absolute risk reduction was 9%. Participants randomized to placebo who initiated oral treprostinil after clinical worsening and tolerated treatment through week 48 demonstrated favorable shifts in functional class (p < 0.0001), 6MWD improvements of + 84 m (p < 0.0001), and a reduction in NT-proBNP of - 778 pg/mL (p = 0.02), compared to OLE baseline. Modest trends toward benefit were measured for those initially assigned placebo who did not have clinical worsening, and 132/144 (92%) of treprostinil assigned participants without clinical worsening remained on drug at week 48 in the OLE study. Adverse events were consistent with FREEDOM-EV.
conclusionInitial treprostinil assignment improved survival in the entire data set; those who began treprostinil after a clinical worsening in the placebo arm and tolerated drug to week 48 enjoyed substantial functional gains. CLINICAL
trial registrationClinicalTrials.gov identifier NCT01560637.
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