Evaluation of losmapimod in patients with chronic obstructive pulmonary disease (COPD) with systemic inflammation stratified using fibrinogen (‘EVOLUTION’): Rationale and protocol
Joint first authors.
- https://doi.org/10.1016/j.artres.2013.10.380How to use a DOI?
- COPD, Losmapimod, p38 MAPK inhibitor, Fibrinogen, Inflammation, 18F-FDG PET/CT
Introduction: p38 mitogen-activated protein kinases (MAPK) are key signalling molecules in cellular responses to external stresses, regulate pro-inflammatory cytokine expression and are implicated in the inflammatory pathogenesis of Chronic Obstructive Pulmonary Disease (COPD) and atherosclerosis. The EVOLUTION trial is a randomised, double-blind, placebo-controlled, Phase 2a trial recruiting from two UK centres that aims to evaluate the effects of Losmapimod (GW856553), a potent oral p38α/β MAPK inhibitor in COPD patients stratified by a fibrinogen level >2.8 g/L.
Methods: Patients are randomised to 7.5 mg losmapimod or matching placebo tablets twice daily for four months. Vascular and pulmonary inflammation is assessed by 18F-FDG PET/CT at baseline and following treatment. Other endpoints including flow-mediated dilatation, aortic pulse wave velocity, spirometry, six-minute walk distance and blood biomarkers of inflammation, are evaluated pre- and post-treatment.
Results: The primary endpoints following 16 weeks treatment include, 1) change in arterial inflammation measured by 18F-FDG PET/CT signal in the aorta and carotid arteries, 2) change in atheromatous plaque and aortic wall characterisation evaluated by 18F-FDG PET/CT and MRI, and 3) change in flow-mediated dilatation.
Key secondary endpoints include change in 1) pulmonary inflammation evaluated by 18F-FDG PET/CT, 2) change in respiratory and physical function indices, 3) arterial stiffness, and 4) measures of systemic biomarkers. Safety endpoints include serious and non-serious adverse events, clinical laboratory results and ECGs.
Discussion: Data gained from the EVOLUTION trial will provide novel information on pulmonary and extra-pulmonary effects of losmapimod in inflammatory disease, in a COPD population with evidence of systemic inflammation.
- © 2013 Association for Research into Arterial Structure and Physiology. Published by Elsevier B.V. All rights reserved.
- Open Access
- This is an open access article distributed under the CC BY-NC license.
Cite this article
TY - JOUR AU - M. Fisk AU - D. Mohan AU - J. Cheriyan AU - L. Yang AU - J. Fuld AU - C.M. McEniery AU - R. Tal-Singer AU - M.I. Polkey AU - I.B. Wilkinson PY - 2013 DA - 2013/11 TI - Evaluation of losmapimod in patients with chronic obstructive pulmonary disease (COPD) with systemic inflammation stratified using fibrinogen (‘EVOLUTION’): Rationale and protocol JO - Artery Research SP - 24 EP - 34 VL - 8 IS - 1 SN - 1876-4401 UR - https://doi.org/10.1016/j.artres.2013.10.380 DO - https://doi.org/10.1016/j.artres.2013.10.380 ID - Fisk2013 ER -