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Clinical Investigations: DIFFUSE DISEASES |

Treprostinil, a Prostacyclin Analogue, in Pulmonary Arterial Hypertension Associated With Connective Tissue Disease*

Ronald J. Oudiz, MD; Robert J. Schilz, DO, PhD, FCCP; Robyn J. Barst, MD; Nazzareno Galié, MD; Stuart Rich, MD, FCCP; Lewis J. Rubin, MD, FCCP; Gérald Simonneau, MD; on behalf of the Treprostinil Study Group
Author and Funding Information

Affiliations: *From the Research and Education Institute (Dr. Oudiz), Harbor-UCLA Medical Center, Torrance, CA; Case Western Reserve University (Dr. Schilz), University Hospitals of Cleveland, Cleveland, OH; Columbia University College of Physicians & Surgeons (Dr. Barst), New York Presbyterian Hospital, New York, NY; Institute of Cardiology (Dr. Galié), University of Bologna, Bologna, Italy; Center for Pulmonary Heart Disease (Dr. Rich), Rush-Presbyterian St. Lukes Medical Center, Chicago, IL; UCSD Medical Center (Dr. Rubin), University of California, San Diego, San Diego, CA; and Service de Pneumologie (Dr. Simonneau), Hôpital Antoine Béclère, Clamart, France.,  A list of study participants is given in the Appendix.

Correspondence to: Ronald J. Oudiz, MD, Harbor-UCLA Medical Center, 1124 W Carson St, #405, Torrance, CA 90502; e-mail: oudiz@humc.edu



Chest. 2004;126(2):420-427. doi:10.1378/chest.126.2.420
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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/m2 in the treprostinil group and − 0.07 ± 0.07 L/min/m2 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.

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