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

J Cardiovasc Pharmacol. 2004 Nov;44 Suppl 1:S80-4. doi: 10.1097/01.fjc.0000166207.74178.d0.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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