Double-blind, placebo-controlled clinical trial with a rho-kinase inhibitor in pulmonary arterial hypertension–A pilot efficacy trial–

Y Fukumoto, N Yamada, H Matsubara… - Circulation …, 2013 - jstage.jst.go.jp
Y Fukumoto, N Yamada, H Matsubara, M Mizoguchi, K Uchino, A Yao, Y Kihara, M Kawano…
Circulation Journal, 2013jstage.jst.go.jp
Background: We have previously demonstrated that long-term inhibition of Rho-kinase
ameliorates pulmonary arterial hypertension (PAH) in animal models. In the present study,
we examined the clinical effects of mid-term oral treatment with an extended release
formulation of AT-877 (fasudil hydrochloride), a specific Rho-kinase inhibitor (AT-877ER) on
PAH. Methods and Results: 23 PAH patients were treated with either placebo (10/2
females/males, 51±16 years, idiopathic PAH (IPAH) in 6, PAH associated with connective …
Background
We have previously demonstrated that long-term inhibition of Rho-kinase ameliorates pulmonary arterial hypertension (PAH) in animal models. In the present study, we examined the clinical effects of mid-term oral treatment with an extended release formulation of AT-877 (fasudil hydrochloride), a specific Rho-kinase inhibitor (AT-877ER) on PAH.
Methods and Results
23 PAH patients were treated with either placebo (10/2 females/males, 51±16 years, idiopathic PAH (IPAH) in 6, PAH associated with connective tissue disease (CTD-PAH) in 3, PAH with congenital heart disease (CHD-PAH) in 2, and portal PAH in 1) or AT-877ER (6/5 females/males, 47±14 years, IPAH in 2, CTD-PAH in 5, and CHD-PAH in 4); 3 patients were excluded. We performed a 6-min walk test and right heart catheterization in the remaining 20 patients, before and 3 months after the treatment (placebo n= 11, AT-877ER n= 9). Although there were no significant differences between the 2 groups for the 6-min walk distance, pulmonary hemodynamics tended to be improved in the AT-877ER group, especially the prevalence of improved cardiac index from baseline, which was significantly higher in the AT-877ER than in the placebo group. In the AT-877ER group, serum levels of hydroxyfasudil, an active metabolite of AT-877ER tended to correlate with improvements in the cardiac index and mean pulmonary artery pressure.
Conclusions
Mid-term treatment with oral AT-877ER showed additional improvement in pulmonary hemodynamics in patients with PAH.(Circ J 2013; 77: 2619–2625)
jstage.jst.go.jp