Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease

Ronald J. Oudiz*, Robert J. Schilz, Robyn J. Barst, Nazzareno Galié, Stuart Rich, Lewis J. Rubin, Gérald Simonneau

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

217 Scopus citations


Study objectives: To assess the efficacy and safety of continuous subcutaneous infusion of treprostinil, a stable prostacyclin analogue, for treating pulmonary arterial hypertension (PAH) in patients with connective tissue disease (CTD). Design: Two multicenter, randomized, double-blind, placebo-controlled, prospective trials of treprostinil vs placebo in 470 patients with PAH. Patients: A subset of 90 patients with PAH and CTD, including systemic lupus erythematosus, diffuse scleroderma, limited scleroderma, and mixed CTD/overlap syndrome. Interventions: Patients received either treprostinil (initiated at 1.25 ng/kg/min, and titrated upward) or placebo via continuous subcutaneous infusion. The maximum dose of treprostinil allowed was 22.5 ng/kg/min. Measurements: Six-minute walk (6MW) distance and dyspnea-fatigue scores were determined at baseline, and at 6 weeks and 12 weeks. Hemodynamic measures were obtained at baseline and at 12 weeks. Results: At baseline, most patients had New York Heart Association class III symptoms. The mean baseline 6MW distance was 289 m (range, 60 to 448 m). The mean dose of treprostinil at week 12 was 8.4 ng/kg/min (range, 1.25 to 17.5 ng/kg/min). After 12 weeks, the change in cardiac index from baseline was + 0.2 ± 0.08 L/min/m 2 in the treprostinil group and - 0.07 ± 0.07 L/min/m 2 in the placebo group (p = 0.007). The pulmonary vascular resistance index decreased by 4 ± 2 U × m2 in the treprostinil group and increased by 1 ± 1 U × m2 in the placebo group (p = 0.006). The placebo-corrected median improvement from baseline in 6MW distance was 25 m in treprostinil-treated patients (p = 0.055); this improvement appeared to be dose related. Dyspnea fatigue scores also improved in the treprostinil group compared with the placebo group (p = 0.014). Adverse events included infusion site pain and typical side effects related to prostaglandins, and were tolerated by most patients. Conclusions: Continuous subcutaneous infusion of treprostinil in patients with PAH associated with CTD improved exercise capacity, symptoms of PAH, and hemodynamics.

Original languageEnglish (US)
Pages (from-to)420-427
Number of pages8
Issue number2
StatePublished - Aug 2004


  • Connective tissue disease
  • Hemodynamics
  • Prostacyclin
  • Pulmonary arterial hypertension
  • Remodulin
  • Scleroderma
  • Systemic lupus erythematosus
  • Treprostinil

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease'. Together they form a unique fingerprint.

Cite this