PMID- 20581169
OWN - NLM
STAT- MEDLINE
DCOM- 20101203
LR  - 20240322
IS  - 1535-4970 (Electronic)
IS  - 1073-449X (Print)
IS  - 1073-449X (Linking)
VI  - 182
IP  - 9
DP  - 2010 Nov 1
TI  - Imatinib in pulmonary arterial hypertension patients with inadequate response to 
      established therapy.
PG  - 1171-7
LID - 10.1164/rccm.201001-0123OC [doi]
AB  - RATIONALE: Pulmonary arterial hypertension (PAH) is a progressive condition with 
      a poor prognosis. Platelet-derived growth factor receptor (PDGFR) signaling plays 
      an important role in its pathobiology. OBJECTIVES: To assess safety, 
      tolerability, and efficacy of the PDGFR inhibitor imatinib in patients with PAH. 
      METHODS: Patients with PAH in functional classes II-IV were enrolled in a 24-week 
      randomized, double-blind, placebo-controlled pilot study. Patients received 
      imatinib (an inhibitor of PDGFR activity) 200 mg orally once daily (or placebo), 
      which was increased to 400 mg if the initial dose was well tolerated. The primary 
      endpoints were safety and change from baseline in the 6-minute-walk distance 
      (6MWD). Secondary endpoints included hemodynamics and functional classification. 
      MEASUREMENTS AND MAIN RESULTS: Fifty-nine patients enrolled (imatinib [n = 28]; 
      placebo [n = 31]); 42 completed the study. Dropouts were equally matched between 
      the two groups. In the intention-to-treat (ITT) population there was no 
      significant change in the 6MWD (mean +/- SD) in the imatinib versus placebo group 
      (+22 +/- 63 versus -1.0 +/- 53 m). There was a significant decrease in pulmonary 
      vascular resistance (imatinib -300 +/- 347 versus placebo -78 +/- 269 dynes . s . 
      cm(-)(5), P < 0.01) and increase in cardiac output (imatinib +0.6 +/- 1.2 versus 
      placebo -0.1 +/- 0.9 L/min, P = 0.02). Serious adverse events occurred in 11 
      imatinib recipients (39%) and 7 placebo recipients (23%). Three deaths occurred 
      in each group. Post hoc subgroup analyses suggest that patients with greater 
      hemodynamic impairment may respond better than patients with less impairment. 
      CONCLUSIONS: These data from a Phase II study are consistent with imatinib being 
      well tolerated in patients with PAH, and provide proof of concept for further 
      studies evaluating its safety, tolerability, and efficacy in PAH. Clinical trial 
      registered with www.clinicaltrials.gov (NCT00477269).
FAU - Ghofrani, Hossein A
AU  - Ghofrani HA
AD  - Pulmonary Hypertension Division, Medical Clinic II/V, University Hospital Giessen 
      und Marburg GmbH, Giessen, Germany. ardeschir.ghofrani@innere.med.uni-giessen.de
FAU - Morrell, Nicholas W
AU  - Morrell NW
FAU - Hoeper, Marius M
AU  - Hoeper MM
FAU - Olschewski, Horst
AU  - Olschewski H
FAU - Peacock, Andrew J
AU  - Peacock AJ
FAU - Barst, Robyn J
AU  - Barst RJ
FAU - Shapiro, Shelley
AU  - Shapiro S
FAU - Golpon, Heiko
AU  - Golpon H
FAU - Toshner, Mark
AU  - Toshner M
FAU - Grimminger, Friedrich
AU  - Grimminger F
FAU - Pascoe, Steve
AU  - Pascoe S
LA  - eng
SI  - ClinicalTrials.gov/NCT00477269
GR  - G0502091/MRC_/Medical Research Council/United Kingdom
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20100625
PL  - United States
TA  - Am J Respir Crit Care Med
JT  - American journal of respiratory and critical care medicine
JID - 9421642
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.1 (Receptors, Platelet-Derived Growth Factor)
SB  - IM
MH  - Adult
MH  - Benzamides
MH  - Double-Blind Method
MH  - Exercise Test
MH  - Female
MH  - Humans
MH  - Hypertension, Pulmonary/*drug therapy/physiopathology
MH  - Imatinib Mesylate
MH  - Intention to Treat Analysis
MH  - Lung/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Piperazines/*pharmacology
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Pyrimidines/*pharmacology
MH  - Receptors, Platelet-Derived Growth Factor/drug effects
MH  - Respiratory Function Tests
MH  - Treatment Outcome
PMC - PMC3001259
EDAT- 2010/06/29 06:00
MHDA- 2010/12/14 06:00
PMCR- 2011/05/01
CRDT- 2010/06/29 06:00
PHST- 2010/06/29 06:00 [entrez]
PHST- 2010/06/29 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2011/05/01 00:00 [pmc-release]
AID - 201001-0123OC [pii]
AID - ajrccm18291171 [pii]
AID - 10.1164/rccm.201001-0123OC [doi]
PST - ppublish
SO  - Am J Respir Crit Care Med. 2010 Nov 1;182(9):1171-7. doi: 
      10.1164/rccm.201001-0123OC. Epub 2010 Jun 25.