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Chest. 2004 Aug;126(2):420-7.

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

Author information

1
Research and Education Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA. oudiz@humc.edu

Abstract

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 x m(2) in the treprostinil group and increased by 1 +/- 1 U x m(2) 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.

Comment in

PMID:
15302727
DOI:
10.1378/chest.126.2.420
[Indexed for MEDLINE]

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