Long-term effects of inhaled treprostinil in patients with pulmonary arterial hypertension: the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) study open-label extension.

Inhaled treprostinil improved functional capacity as add-on therapy in the short-term management of patients with pulmonary arterial hypertension (PAH). This study investigated the long-term effects of inhaled treprostinil in patients concurrently receiving oral background therapy. A total of 206 patients (81% women) completing the 12-week double-blind phase of the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) study transitioned into an open-label extension. Patients were assessed every 3 months for changes in 6-minute walk distance (6MWD), Borg dyspnea score, New York Heart Association (NYHA) functional class, quality of life (QOL) scores, and signs and symptoms of PAH. Patients were primarily NYHA class III (86%), with a mean baseline 6MWD of 349 ± 81 meters. A median change in 6MWD of 28, 31, 32, and 18 meters in patients continuing therapy was observed at 6, 12, 18, and 24 months, respectively. This effect was more prominent in those patients originally allocated to active therapy in the double-blind phase. Survival rates for patients remaining on therapy were 97%, 94%, and 91% at 12, 18, and 24 months, respectively. In addition, 82%, 74%, and 69% of patients maintained treatment benefit as evidenced by lack of clinical worsening at 12, 18, and 24 months. The most common adverse events were known effects of prostanoid therapy (headache [34%], nausea [21%], and vomiting [10%]) or were due to the route of administration (cough [53%], pharyngolaryngeal pain [13%], and chest pain [13%]). Long-term therapy with inhaled treprostinil demonstrated persistent benefit for PAH patients who remained on therapy for up to 24 months.

Benza RL ，Seeger W ，McLaughlin VV ，Channick RN ，Voswinckel R ，Tapson VF ，Robbins IM ，Olschewski H ，Rubin LJ ... -  《-》

Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial.

This study assessed the efficacy and safety of inhaled treprostinil in pulmonary arterial hypertension (PAH) patients receiving therapy with either bosentan or sildenafil. There is no cure for PAH, despite effective treatments, and outcomes remain suboptimal. The addition of inhaled treprostinil, a long-acting prostacyclin analog, might be a safe and effective treatment addition to other PAH-specific oral therapies. Two hundred thirty-five PAH patients with New York Heart Association (NYHA) functional class III (98%) or IV symptoms and a 6-min walk distance (6MWD) of 200 to 450 m while treated with bosentan (70%) or sildenafil were randomized to inhaled treprostinil (up to 54 mug) or inhaled placebo 4 times daily. The primary end point was peak 6MWD at 12 weeks. Secondary end points included time to clinical worsening, Borg Dyspnea Score, NYHA functional class, 12-week trough 6MWD, 6-week peak 6MWD, quality of life, and PAH signs and symptoms. The biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) was assessed. Twenty-three patients withdrew from the study prematurely (13 treprostinil, 10 placebo). The Hodges-Lehmann between-treatment median difference in change from baseline in peak 6MWD was 19 m at week 6 (p = 0.0001) and 20 m at week 12 (p = 0.0004). Hodges-Lehmann between-treatment median difference in change from baseline in trough 6MWD at week 12 was 14 m (p = 0.0066). Quality of life measures and NT-proBNP improved on active therapy. There were no improvements in other secondary end points, including time to clinical worsening, Borg Dyspnea Score, NYHA functional class, and PAH signs and symptoms. Inhaled treprostinil was safe and well-tolerated. This trial demonstrates that, among PAH patients who remain symptomatic on bosentan or sildenafil, inhaled treprostinil improves exercise capacity and quality of life and is safe and well-tolerated. (TRIUMPH I: Double Blind Placebo Controlled Clinical Investigation Into the Efficacy and Tolerability of Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension; NCT00147199).

McLaughlin VV ，Benza RL ，Rubin LJ ，Channick RN ，Voswinckel R ，Tapson VF ，Robbins IM ，Olschewski H ，Rubenfire M ，Seeger W ... -  《-》

Safety and efficacy of transition from subcutaneous treprostinil to oral sildenafil in patients with pulmonary arterial hypertension.

Keogh AM ，Jabbour A ，Weintraub R ，Brown K ，Hayward CS ，Macdonald PS ... -  《-》

Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial.

Tapson VF ，Torres F ，Kermeen F ，Keogh AM ，Allen RP ，Frantz RP ，Badesch DB ，Frost AE ，Shapiro SM ，Laliberte K ，Sigman J ，Arneson C ，Galiè N ... -  《-》

One-year experience with intravenous treprostinil for pulmonary arterial hypertension.

Intravenous (IV) epoprostenol has been the mainstay of therapy in advanced pulmonary arterial hypertension (PAH). Continuous IV treprostinil has several potential advantages over IV epoprostenol; however, there has been a lack of published long-term efficacy and safety data on IV treprostinil in PAH. We conducted a 48-week, multicenter, prospective, open-label, uncontrolled, study of continuous IV treprostinil in 16 patients on no prior PAH specific therapy at baseline (de novo), or 31 patients transitioned at baseline from IV epoprostenol (transition). The primary end point was change in exercise capacity assessed by the 6-minute walk distance (6MWD) test. In de novo patients, IV treprostinil increased the mean ± standard error 6MWD by 125 m from 332 ± 21 m at baseline to 457 ± 26 m at Week 48. There were also improvements in the secondary end points of Naughton-Balke treadmill time, Borg Dyspnea Score, and hemodynamics at Week 48 compared with baseline. In 23 patients transitioned from IV epoprostenol with 48-week follow-up data, 6MWD, hemodynamic measures, and World Health Organization functional class at Week 48 were all stable compared with baseline. Side effects were generally mild and consistent with those reported with prostacyclin treatment. During the study, 5 patients died of causes not considered related to the therapy, and 7 discontinued due to adverse events. In this open-label trial, continuous IV treprostinil for 1 year appears to be safe and effective in de novo PAH patients and those transitioned from IV epoprostenol.

Benza RL ，Tapson VF ，Gomberg-Maitland M ，Poms A ，Barst RJ ，McLaughlin VV ... -  《-》