title: Double-blind, placebo-controlled clinical trial with a rho-kinase inhibitor in pulmonary arterial hypertension.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukumoto
authors.forename: Norikazu
authors.initials: N
authors.lastname: Yamada
authors.forename: Hiromi
authors.initials: H
authors.lastname: Matsubara
authors.forename: Minori
authors.initials: M
authors.lastname: Mizoguchi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Uchino
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yao
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kihara
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kawano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takeda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Adachi
authors.forename: Shinobu
authors.initials: S
authors.lastname: Osanai
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tanabe
authors.forename: Teruo
authors.initials: T
authors.lastname: Inoue
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kubo
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ota
authors.forename: Koichiro
authors.initials: K
authors.lastname: Fukuda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakano
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D008168:Lung / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil