PMID- 25703961
DCOM- 20151215
LR  - 20171116
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 34
IP  - 3
DP  - 2015 Mar
TI  - Use of clinically relevant responder threshold criteria to evaluate the response 
      to treatment in the phase III PATENT-1 study.
PG  - 338-47
LID - 10.1016/j.healun.2014.12.001 [doi]
LID - S1053-2498(14)01496-X [pii]
AB  - 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-naive 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-naive 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-naive 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-naive patients and patients on background PAH-targeted
      therapy who fulfilled criteria defining a positive response to therapy.
CI  - Copyright (c) 2015 International Society for Heart and Lung Transplantation.
      Published by Elsevier Inc. All rights reserved.
FAU - Langleben, David
AU  - Langleben D
AD  - Center for Pulmonary Vascular Disease and Lady Davis Institute, Jewish General
      Hospital, McGill University, Montreal, Canada. Electronic address:
FAU - Galie, Nazzareno
AU  - Galie N
AD  - Department of Experimental, Diagnostic and Specialty Medicine, Bologna University
      Hospital, Bologna, Italy.
FAU - He, Jianguo
AU  - He J
AD  - 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.
FAU - Huang, Yigao
AU  - Huang Y
AD  - Department of Cardiology, Guangdong General Hospital and Guangdong Cardiovascular
      Institute, Guangzhou, Guangdong, China.
FAU - Humbert, Marc
AU  - Humbert M
AD  - Assistance Publique-Hopitaux de Paris, Service de Pneumologie, Hopital Bicetre,
      Universite Paris-Sud, Laboratoire d'Excellence en Recherche sur le Medicament et 
      Innovation Therapeutique, and INSERM Unite 999, Le Kremlin-Bicetre, France.
FAU - Keogh, Anne
AU  - Keogh A
AD  - St Vincent's Hospital, Sydney, New South Wales, Australia.
FAU - Rubin, Lewis J
AU  - Rubin LJ
AD  - University of California, San Diego, La Jolla, California.
FAU - Zhou, Daxin
AU  - Zhou D
AD  - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai
      Institute of Cardiovascular Diseases, Shanghai, China.
FAU - Curram, John
AU  - Curram J
AD  - Global Development, Bayer Pharma AG, Newbury, United Kingdom.
FAU - Davie, Neil
AU  - Davie N
AD  - Global Clinical Development, Bayer Pharma AG, Wuppertal, Germany.
FAU - Ghofrani, Hossein-Ardeschir
AU  - Ghofrani HA
AD  - University of Giessen and Marburg Lung Center, Giessen, Germany, German Center of
      Lung Research, and Department of Medicine, Imperial College London, London,
      United Kingdom.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20141212
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - RU3FE2Y4XI (riociguat)
SB  - IM
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Exercise Test/drug effects
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Hypertension, Pulmonary/*drug therapy/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Pyrazoles/*administration & dosage
MH  - Pyrimidines/*administration & dosage
MH  - Treatment Outcome
MH  - Ventricular Function, Right/drug effects/*physiology
MH  - Ventricular Pressure/*drug effects
MH  - Walking/*physiology
OT  - pulmonary arterial hypertension
OT  - responder threshold criteria
OT  - riociguat
OT  - soluble guanylate cyclase stimulator
OT  - treatment response
EDAT- 2015/02/24 06:00
MHDA- 2015/12/17 06:00
CRDT- 2015/02/24 06:00
PHST- 2014/10/24 00:00 [received]
PHST- 2014/12/03 00:00 [revised]
PHST- 2014/12/06 00:00 [accepted]
PHST- 2015/02/24 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
AID - S1053-2498(14)01496-X [pii]
AID - 10.1016/j.healun.2014.12.001 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2015 Mar;34(3):338-47. doi:
      10.1016/j.healun.2014.12.001. Epub 2014 Dec 12.