title: Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is a progressive, fatal disease with no cure. Parenteral and inhaled prostacyclin analogue therapies are effective for the treatment of PAH, but complicated administration requirements can limit the use of these therapies in patients with less severe disease. This study was designed to evaluate the safety and efficacy of the oral prostacyclin analogue treprostinil diolamine as initial treatment for de novo PAH.
  
  
  RESULTS
  Three hundred forty-nine patients (intent-to-treat population) not receiving endothelin receptor antagonist or phosphodiesterase type-5 inhibitor background therapy were randomized (treprostinil, n=233; placebo, n=116). The primary analysis population (modified intent-to-treat) included 228 patients (treprostinil, n=151; placebo, n=77) with access to 0.25-mg treprostinil tablets at randomization. The primary end point was change from baseline in 6-minute walk distance at week 12. Secondary end points included Borg dyspnea index, clinical worsening, and symptoms of PAH. The week 12 treatment effect for 6-minute walk distance (modified intent-to-treat population) was 23.0 m (P=0.0125). For the intent-to-treat population, 6-minute walk distance improvements were observed at peak (26.0 m; P=0.0001) and trough (17.0 m; P=0.0025) plasma study drug concentrations. Other than an improvement in the combined 6-minute walk distance/Borg dyspnea score, there were no significant changes in secondary end points. Oral treprostinil therapy was generally well tolerated; the most common adverse events (intent-to-treat) were headache (69%), nausea (39%), diarrhea (37%), and pain in jaw (25%).
  
  
  CONCLUSIONS
  Oral treprostinil improves exercise capacity in PAH patients not receiving other treatment. Oral treprostinil could provide a convenient, first-line prostacyclin treatment option for PAH patients not requiring more intensive therapy.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00325403.
authors: Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Rd, Yangpu District, Shanghai, China 20043. jingzhicheng@gmail.com
authors: Zhi-Cheng
authors: ZC
authors: Jing
authors: Keyur
authors: K
authors: Parikh
authors: Tomas
authors: T
authors: Pulido
authors: Carlos
authors: C
authors: Jerjes-Sanchez
authors: R James
authors: RJ
authors: White
authors: Roblee
authors: R
authors: Allen
authors: Adam
authors: A
authors: Torbicki
authors: Kai-Feng
authors: KF
authors: Xu
authors: David
authors: D
authors: Yehle
authors: Kevin
authors: K
authors: Laliberte
authors: Carl
authors: C
authors: Arneson
authors: Lewis J
authors: LJ
authors: Rubin
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D002648:Child; D004417:Dyspnea / Q000453:epidemiology; D011464:Epoprostenol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017079:Exercise Tolerance / Q000502:physiology; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D015994:Incidence; D007391:International Cooperation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D016138:Walking / Q000502:physiology; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D011464:Epoprostenol; C427248:treprostinil