title: Use of clinically relevant responder threshold criteria to evaluate the response to treatment in the phase III PATENT-1 study.
abstract: BACKGROUND
  In PATENT-1, riociguat significantly improved 6-minute walking distance (6MWD) and a range of secondary end-points in patients with pulmonary arterial hypertension (PAH). We investigated whether riociguat increased the proportion of patients achieving clinically relevant responder thresholds compared with placebo during PATENT-1.
  
  
  METHODS
  In PATENT-1, a randomized, double-blind study, treatment-naïve patients or patients on background PAH-targeted therapy with symptomatic PAH received 12 weeks of treatment with placebo, riociguat up to 2.5 mg 3 times daily, or riociguat up to 1.5 mg 3 times daily. Increases in 6MWD ≥40 m, 6MWD ≥380 m, cardiac index ≥2.5 liter/min/m(2), mixed venous oxygen saturation ≥65%, World Health Organization functional class I/II, N-terminal pro-brain natriuretic peptide <1,800 pg/ml, and right atrial pressure <8 mm Hg were chosen as threshold criteria of a positive response.
  
  
  RESULTS
  Riociguat increased the proportion of treatment-naïve patients and patients on background PAH-targeted therapy with 6MWD ≥380 m at Week 12 (+21% and +15%, respectively), whereas there was a small reduction in 6MWD in placebo-treated patients for both sub-groups. Riociguat also increased the proportion of treatment-naïve patients and patients on background PAH-targeted therapy achieving World Health Organization functional class I/II (+12% and +19%, respectively) and cardiac index ≥2.5 liter/min/m(2) (+30% and +33%, respectively) at Week 12, whereas there was little change in the respective placebo groups.
  
  
  CONCLUSIONS
  Compared with placebo, riociguat increased the proportion of treatment-naïve patients and patients on background PAH-targeted therapy who fulfilled criteria defining a positive response to therapy.
authors.affiliation: Center for Pulmonary Vascular Disease and Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Canada. Electronic address: david.langleben@mcgill.ca.
authors.forename: David
authors.initials: D
authors.lastname: Langleben
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Bologna University Hospital, Bologna, Italy.
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Galiè
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Cardiology, Guangdong General Hospital and Guangdong Cardiovascular Institute, Guangzhou, Guangdong, China.
authors.forename: Yigao
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Université Paris-Sud, Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique, and INSERM Unité 999, Le Kremlin-Bicêtre, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: St Vincent's Hospital, Sydney, New South Wales, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Keogh
authors.affiliation: University of California, San Diego, La Jolla, California.
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
authors.affiliation: Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China.
authors.forename: Daxin
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Global Development, Bayer Pharma AG, Newbury, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Curram
authors.affiliation: Global Clinical Development, Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Neil
authors.initials: N
authors.lastname: Davie
authors.affiliation: University of Giessen and Marburg Lung Center, Giessen, Germany, German Center of Lung Research, and Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Hossein-Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
mesh_terms: D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005080:Exercise Test / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D016896:Treatment Outcome; D016278:Ventricular Function, Right / Q000187:drug effects / Q000502:physiology*; D017725:Ventricular Pressure / Q000187:drug effects*; D016138:Walking / Q000502:physiology*
chemical_list: D011720:Pyrazoles; D011743:Pyrimidines; C542595:riociguat
keywords: pulmonary arterial hypertension; responder threshold criteria; riociguat; soluble guanylate cyclase stimulator; treatment response