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

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.

• Authors: Ronald J Oudiz, Robert J Schilz, Robyn J Barst, Nazzareno Galié, Stuart Rich, Lewis J Rubin, Gérald Simonneau, Treprostinil Study Group
• Journal: Chest (Chest) Vol. 126 Issue 2 Pg. 420-7 (Aug 2004) ISSN: 0012-3692 [Print] United States
• PMID: 15302727 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Epoprostenol
• treprostinil

Topics

• Adolescent
• Adult
• Aged
• Child
• Connective Tissue Diseases (complications)
• Double-Blind Method
• Epoprostenol (administration & dosage, analogs & derivatives, therapeutic use)
• Exercise Tolerance
• Female
• Hemodynamics (physiology)
• Humans
• Hypertension, Pulmonary (drug therapy)
• Infusions, Intravenous
• Injections, Subcutaneous
• Lupus Erythematosus, Systemic (complications)
• Male
• Middle Aged
• Mixed Connective Tissue Disease (complications)
• Prospective Studies
• Scleroderma, Limited (complications)
• Scleroderma, Systemic (complications)
• Treatment Outcome
• Walking