Oral Treprostinil for the Treatment of Pulmonary Arterial Hypertension in Patients Receiving Background Endothelin Receptor Antagonist and Phosphodiesterase Type 5 Inhibitor Therapy (The FREEDOM-C2 Study) A Randomized Controlled Trial

被引:240
作者
Tapson, Victor F. [1 ]
Jing, Zhi-Cheng [3 ]
Xu, Kai-Feng [4 ]
Pan, Lei [5 ]
Feldman, Jeremy [6 ]
Kiely, David G. [7 ,8 ]
Kotlyar, Eugene [9 ]
McSwain, C. Shane [2 ]
Laliberte, Kevin [2 ]
Arneson, Carl [2 ]
Rubin, Lewis J. [10 ]
机构
[1] Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA
[2] United Therapeutics Corp, Res Triangle Pk, NC USA
[3] Tongji Univ, Sch Med, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China
[4] Beijing Union Med Coll Hosp, Beijing, Peoples R China
[5] Capital Med Univ, Beijing Shijitan Hosp, Dept Pulm Vasc Dis, Beijing, Peoples R China
[6] Arizona Pulm Specialists Ltd, Phoenix, AZ USA
[7] Natl Inst Hlth Res, Cardiovasc Biomed Res Unit, Sheffield, S Yorkshire, England
[8] Sheffield Teaching Hosp NHS Fdn Trust, Royal Hallamshire Hosp, Sheffield Pulm Vasc Dis Unit, Sheffield, S Yorkshire, England
[9] St Vincents Hosp, Heart Lung Clin, Sydney, NSW 2010, Australia
[10] UC San Diego Med Ctr, San Diego, CA USA
关键词
SUBCUTANEOUS INFUSION; INHALED ILOPROST; DOUBLE-BLIND; SILDENAFIL; EFFICACY; BOSENTAN;
D O I
10.1378/chest.12-2875
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background: Treprostinil is a stable prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) as parenteral or inhaled therapy. Treprostinil diolamine, a sustained-release oral formulation of treprostinil, was studied to determine whether it could provide a more convenient prostacyclin treatment option for patients with less severe PAH. The objective of this study was to evaluate the efficacy and safety of oral treprostinil in patients with PAH receiving stable background endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor (PDE-5I) therapy, or both. Methods: A 16-week, multicenter, double-blind, placebo-controlled study in 310 patients with PAH compared bid administration of oral treprostinil (n = 157) with placebo (n = 153). The primary end point was change in 6-min walk distance at week 16. Secondary efficacy end points were World Health Organization functional class, Borg dyspnea score, dyspnea-fatigue index, signs and symptoms of PAH, and clinical worsening. Results: One hundred thirty-two patients (84%) receiving oral treprostinil and 138 (90%) receiving placebo completed the study. The mean +/- SD dose of oral treprostinil at week 16 was 3.1 +/- 1.9 mg bid. The Hodges-Lehmann placebo-corrected median difference in 6MWD at week 16 was 10.0 m (95% CI, 2 2 to 22 m; P = .089). There were no significant changes in secondary end points. The most common adverse events associated with oral treprostinil were headache (71%), diarrhea (55%), nausea (46%), flushing (35%), and jaw pain (25%). Conclusions: The addition of oral treprostinil to background ERA and PDE-5I therapy did not result in a statistically significant improvement in exercise capacity. Side effects were common but tolerated by most subjects.
引用
收藏
页码:952 / 958
页数:7
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