STRIDE 1: effects of the selective ET(A) receptor antagonist, sitaxsentan sodium, in a patient population with pulmonary arterial hypertension that meets traditional inclusion criteria of previous pulmonary arterial hypertension trials.

Abstract

Sitaxsentan (SITAX; Thelin, Encysive Corporation, Bellaire, TX, U.S.A.) is a highly selective oral endothelin-A receptor antagonist. STRIDE-1, a 12-week randomized, doubleblind, placebo-controlled trial of sitaxsentan for pulmonary arterial hypertension showed significant benefit in 6-minute walk distance, functional class and hemodynamics. Pulmonary arterial hypertension clinical trials traditionally limit enrolment to class III/IV patients with idiopathic pulmonary arterial hypertension or pulmonary arterial hypertension related to connective tissue disease, who have a baseline 6-minute walk distance of < 450 m. In contrast, STRIDE-1 included milder cases: class II patients, no baseline 6- minute walk cut-off, and congenital heart disease patients. We now present the STRIDE-1 subset who would have qualified under traditional inclusion criteria. The results were: change for placebo (mean +/- SE) vs change for sitaxsentan (mean +/- SE) vs treatment effect (mean), all statistically significant: 6-minute walk (m): -26 +/- 13, 39 +/- 10, 65; mean right atrial pressure (mmHg): 2.1 +/- 0.8, -1.2 +/- 0.5, -3.3; mean pulmonary arterial pressure (mmHg): 0.4 +/- 1.5, -4.7 +/- 1.5, -5.1; cardiac index (L/min per m): -0.09 +/- 0.09, 0.38 +/- 0.06, 0.47; pulmonary vascular resistance (dyne.s.cm): 85 +/- 60, -274 +/- 47, -359. A 45% improvement in functional class was seen in sitaxsentan-treated patients (P = 0.0005). Thus, in the STRIDE-1 subpopulation that met enrolment criteria of previous pulmonary arterial hypertension trials, improvement in efficacy parameters with sitaxsentan therapy was even greater than seen in the entire STRIDE-1 population.

• Authors: David Langleben, Tommy Brock, Richard Dixon, Robyn Barst, STRIDE-1 study group
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 44 Suppl 1 Pg. S80-4 (Nov 2004) ISSN: 1533-4023 [Electronic] United States
• PMID: 15838366 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Endothelin A Receptor Antagonists
• Isoxazoles
• Thiophenes
• sitaxsentan

Topics

• Administration, Oral
• Adult
• Aged
• Antihypertensive Agents (administration & dosage, adverse effects, therapeutic use)
• Blood Pressure (drug effects)
• Canada
• Double-Blind Method
• Endothelin A Receptor Antagonists
• Exercise Tolerance (drug effects)
• Female
• Humans
• Hypertension, Pulmonary (drug therapy, physiopathology)
• Isoxazoles (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Patient Selection
• Severity of Illness Index
• Thiophenes (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome
• United States
• Vascular Resistance (drug effects)
• Walking