PAH-CTD is progressive, difficult to manage, and the leading cause of death in CTD. Endothelin levels are increased in PAH-CTD and have vasoconstrictive and proliferative effects primarily mediated by the smooth muscle cell ETA receptor. Sitaxsentan (SITAX) is a pharmacologically distinct, oral, once-daily, highly selective (6500:1) endothelin ETA receptor antagonist. We previously reported that PAH-CTD patients (pts) in STRIDE-1, a 12 wk, MC, DB, placebo (PBO) controlled trial improved 6MW (58m; p=0.0274), NYHA functional class (NYHA FC) and hemodynamics. For the first time, we report on the long-term follow-up of the PAH-CTD subgroup during the STRIDE-1X extension study.
STRIDE-1 evaluated SITAX 100mg, 300 mg, and PBO. Due to similar treatment effects in total ITT population, the SITAX 100mg and 300mg groups were pooled. After STRIDE-1, pts could enter the blinded STRIDE-1X and were treated with either SITAX 100mg or 300mg. Pts on PBO were re-randomized to either SITAX 100mg or 300mg. NYHA FC data were collected in STRIDE-1X. A post hoc analysis was performed to evaluate the effect of SITAX in the intent-to-treat PAH-CTD subgroup. At baseline, 42 of 178 pts had PAH-CTD and were NYHA FC II or III. 41 pts entered STRIDE-1X.
Median and mean treatment was 26 weeks, maximum 55 weeks. Overall, 22 (54%) pts improved by more than one NYHA FC with 11 (50%) pts reporting first improvement during the week 0-12 and 11 (50%) during week 12-52. Two (5%) pts deteriorated by one or more NYHA FC, both occuring by week 4. Both doses of sitaxsentan were well tolerated. One pt (5%) in each group reported liver function abnormalities >3xULN during the entire treatment course. 5 pts discontinued during the study.
Short-term treatment with SITAX improves NYHA FC. First time improvements in NYHA FC may also occur late in treatment. Long-term treatment with SITAX is well tolerated.
SITAX has a favorable safety and efficacy profile in pts with PAH-CTD.
Reda Girgis, Grant monies (from industry related sources) Encysive Pharmaceuticals; Consultant fee, speaker bureau, advisory committee, etc. Encysive Pharmaceuticals; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. sitaxsentan.