PMID- 28090293
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2045-8932 (Print)
IS  - 2045-8940 (Electronic)
IS  - 2045-8932 (Linking)
VI  - 6
IP  - 4
DP  - 2016 Dec
TI  - Relevance of angiopoietin-2 and soluble P-selectin levels in patients with 
      pulmonary arterial hypertension receiving combination therapy with oral 
      treprostinil: a FREEDOM-C2 biomarker substudy.
PG  - 516-523
LID - 10.1086/688671 [doi]
AB  - Studies have suggested roles for angiopoietin-2 (Ang-2) and soluble P-selectin 
      (sP-selectin) as biomarkers of disease severity and treatment response in 
      pulmonary arterial hypertension (PAH), but additional data are required for 
      validation. We evaluated these biomarkers using data from FREEDOM-C2, in which 
      patients with PAH receiving stable monotherapy or combination therapy were 
      randomized to receive additional treatment with oral treprostinil (up-titrated 
      from 0.25 mg twice daily) or placebo for 16 weeks. Biomarker analysis was 
      optional in FREEDOM-C2. We measured plasma Ang-2 and sP-selectin levels at 
      baseline and at week 16, and we assessed their association with predefined 
      outcomes (6-minute walk distance [6MWD] change from baseline >40 m, 6MWD >380 m, 
      functional class I/II, and/or N-terminal pro-brain natriuretic peptide 
      [NT-proBNP] <1,800 pg/mL at week 16) using Spearman correlation, receiver 
      operating characteristics, and logistic regression. Biomarker data were available 
      for 83 of 157 and 95 of 153 patients in the oral treprostinil and placebo groups, 
      respectively. In the oral treprostinil group, baseline Ang-2 levels correlated 
      with week 16 NT-proBNP levels (P < 0.0001). Baseline Ang-2 >/=12 ng/mL was 
      associated with a reduced likelihood of having NT-proBNP <1,800 pg/mL at week 16 
      (multivariate odds ratio: 0.08; 95% confidence interval: 0.02-0.32). However, 
      Ang-2 showed no significant association with the other assessed outcomes, and 
      sP-selectin was not associated or correlated with any of the outcomes. These data 
      suggest that Ang-2 and sP-selectin are not associated with response to oral 
      treprostinil in patients already receiving stable PAH therapy. TRIAL 
      REGISTRATION: Clinicaltrials.gov identifier NCT00887978.
FAU - Richter, Manuel J
AU  - Richter MJ
AD  - Department of Pneumology, Kerckhoff Heart and Thoracic Center, Bad Nauheim, 
      Germany; Department of Internal Medicine, Justus Liebig University Giessen, 
      Universities of Giessen and Marburg Lung Center, Giessen, Germany.
FAU - Schermuly, Ralph
AU  - Schermuly R
AD  - Department of Internal Medicine, Justus Liebig University Giessen, Universities 
      of Giessen and Marburg Lung Center, Giessen, Germany.
FAU - Seeger, Werner
AU  - Seeger W
AD  - Department of Internal Medicine, Justus Liebig University Giessen, Universities 
      of Giessen and Marburg Lung Center, Giessen, Germany.
FAU - Rao, Youlan
AU  - Rao Y
AD  - United Therapeutics, Research Triangle Park, North Carolina, USA.
FAU - Ghofrani, Hossein A
AU  - Ghofrani HA
AD  - Department of Pneumology, Kerckhoff Heart and Thoracic Center, Bad Nauheim, 
      Germany; Department of Internal Medicine, Justus Liebig University Giessen, 
      Universities of Giessen and Marburg Lung Center, Giessen, Germany; Department of 
      Medicine, Imperial College London, London, United Kingdom.
FAU - Gall, Henning
AU  - Gall H
AD  - Department of Internal Medicine, Justus Liebig University Giessen, Universities 
      of Giessen and Marburg Lung Center, Giessen, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT00887978
PT  - Journal Article
PL  - United States
TA  - Pulm Circ
JT  - Pulmonary circulation
JID - 101557243
PMC - PMC5210055
OTO - NOTNLM
OT  - angiopoietin-2
OT  - granule membrane protein 140
OT  - prostacyclin
OT  - pulmonary hypertension
EDAT- 2017/01/17 06:00
MHDA- 2017/01/17 06:01
PMCR- 2016/12/01
CRDT- 2017/01/17 06:00
PHST- 2017/01/17 06:00 [entrez]
PHST- 2017/01/17 06:00 [pubmed]
PHST- 2017/01/17 06:01 [medline]
PHST- 2016/12/01 00:00 [pmc-release]
AID - PC2013340 [pii]
AID - 10.1086/688671 [doi]
PST - ppublish
SO  - Pulm Circ. 2016 Dec;6(4):516-523. doi: 10.1086/688671.