Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study.
OBJECTIVE
To evaluate the safety and efficacy of sitaxsentan, an endothelin-A receptor antagonist, in a 12-week, open-label trial of patients with pulmonary arterial hypertension (PAH).


METHODS
Six children and 14 adults with New York Heart Association (NYHA) functional class II, III, or IV primary pulmonary hypertension or PAH associated with either congenital systemic-to-pulmonary shunts or collagen vascular disease were enrolled.


METHODS
Sitaxsentan was administered orally at 100 to 500 mg bid for 12 weeks. Cardiopulmonary hemodynamics via cardiac catheterization were obtained at baseline and week 12. Six-minute walk test distance was measured at baseline, week 6, and week 12.


RESULTS
Sitaxsentan treatment resulted in significant improvement in exercise capacity as assessed by the 6-min walk distance (baseline [mean +/- SD], 466 +/- 132 m; week 12, 515 +/- 141 m, n = 20, p = 0.006). Mean pulmonary artery pressure and pulmonary vascular resistance index also improved (63 +/- 20 to 52 +/- 22 mm Hg, n = 17, p = 0.0002; and 20 +/- 11 to 14 +/- 13 U x m(2), n = 17, p = 0.008, respectively). Serious adverse events included two cases of acute hepatitis (fatal in one patient).


CONCLUSIONS
Patients with NYHA functional class II, III, or IV PAH showed a significant improvement in exercise capacity and cardiopulmonary hemodynamics over a 12-week period of treatment with sitaxsentan, an endothelin-A receptor antagonist. Further investigation is warranted to evaluate the safety and efficacy of sitaxsentan in patients with PAH.
Barst
Robyn J
RJ
Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
Rich
Stuart
S
Widlitz
Allison
A
Horn
Evelyn M
EM
McLaughlin
Vallerie
V
McFarlin
Joyce
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D065128:Endothelin Receptor Antagonists; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D044022:Receptor, Endothelin A; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*
D065128:Endothelin Receptor Antagonists; D007555:Isoxazoles; D044022:Receptor, Endothelin A; D013876:Thiophenes; C106276:sitaxsentan