Effect of Fostair® on Biomarkers of Platelet Adhesion in Idiopathic Pulmonary Fibrosis
Status:
Completed
Trial end date:
2015-05-01
Target enrollment:
Participant gender:
Summary
The investigator has recently studied markers of platelet activation in idiopathic pulmonary
fibrosis (IPF) and found that in IPF patients there is a significantly increased platelet
reactivity when compared with controls which is demonstrated by a concentration dependent
increase in platelet-monocyte complex formation, platelet P-selectin expression and platelet
fibrinogen binding in the presence of' the platelet agonists Adenosine diphosphate and L-
Threonyl- L- phenylalanyl- L- leucyl- L- leucyl- L-argininamide (TFLLR).
During platelet activation the platelets degranulate releasing numerous profibrotic cytokines
including Transforming growth factor beta and Platelet derived growth factor that are
recognised to be important in the pathogenesis of IPF. It is therefore plausible that the
observed increased platelet reactivity in IPF contributes to the fibrotic process through
local activation and degranulation with release of proinflammatory and profibrotic mediators
within the pulmonary circulation.
There is evidence that corticosteroid treatment may alter platelet adhesion, in a study of
spontaneously hypertensive rat (SHR) increased circulating glucocorticoid, suppressed
p-selectin expression. p selectin is a transmembrane protein present in the α granules of
platelets. P selectin has a crucial role in platelet aggregation and platelet-leukocyte
interactions, which are both potentially important mechanisms in the initiation and/or
progression of tissue injury and development of thrombosis. In a study of patients with
chronic obstructive pulmonary disease (COPD) exacerbation these were treated with either β
agonists alone or β agonist and 40mg prednisolone and compared with a control group. At
presentation the COPD patients had higher pulmonary artery pressure (PAP) higher p selectin
and fibrinogen levels but lower Antithrombin III levels (AT III). The pulmonary artery
pressure and fibrinogen levels were found to be significantly decreased in the steroid
treated group whilst the p-selectin levels further increased in the non steroidal therapy
patients.
Rationale for the Current Study
There is a significant unmet medical need for the treatment of IPF; the only medication
approved for treatment of IPF in the United Kingdom (UK) is Pirfenidone and outside the UK
there is none. The main goal of the current study is to evaluate the effect of Fostair on the
biomarkers of platelet activation in IPF disease which the investigator believes play a
pivotal role in the pathogenesis of IPF and whether this translates in to a clinically
beneficial effect of Fostair on IPF disease.
Phase:
Phase 2
Details
Lead Sponsor:
Hull and East Yorkshire Hospitals NHS Trust Hull University Teaching Hospitals NHS Trust