Effect of Fostair® on Biomarkers of Platelet Adhesion in Idiopathic Pulmonary Fibrosis
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|ClinicalTrials.gov Identifier: NCT02048644|
Recruitment Status : Completed
First Posted : January 29, 2014
Last Update Posted : July 15, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Idiopathic Pulmonary Fibrosis||Drug: fostair Drug: placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Randomized, Double-blind, Placebo-controlled, Crossover Study to Assess the Effect of 28 Day Treatment With Fostair® Pressurized Metered-dose Inhaler (pMDI) 200/12 on Biomarkers of Platelet Adhesion in Patients With Idiopathic Pulmonary Fibrosis|
|Study Start Date :||March 2014|
|Actual Primary Completion Date :||April 2015|
|Actual Study Completion Date :||May 2015|
Placebo Comparator: placebo inhaler
matched placebo inhaler, to be taken 2 puffs, twice a day for 28 days
placebo matched inhaler 2puffs to be taken twice a day for 28 days
fostair 100mcg/6mcg 2pufss, twice a day.
beclometasone dipropionate 200mcg and formoterol 12 mcg delivered by inhaler, twice a day for 28 days
Other Name: beclometasone dipropionate and formoterol fumarate
- platelet-monocyte complex formation [ Time Frame: 1 month ]Measurements will include platelet-monocyte complex formation measured at baseline, and post investigational treatments at Visit 5 and visit 8.
- platelet P-selectin expression [ Time Frame: 1 month ]platelet p selectin expression will be measured at baseline, and post investigational treatments at Visit 5 and visit 8.
- platelet fibrinogen binding [ Time Frame: 1 month ]Platelet fibrinogen binding will be measured at baseline, and post investigational treatments at Visit 5 and visit 8.
- forced vital capacity [ Time Frame: visit1, visit 5 and visit 8 ]forced vital capacity will be measured at baseline and then at visit 5 and visit 8 following 1 months treatment of fostair or placebo
- sputum eosinophils cells [ Time Frame: 1 month ]inflammatory cells will be measured at baseline, and post investigational treatments at Visit 5 and visit 8.
- six minute walk distance [ Time Frame: 1 month ]six minute walk distance will be measured at baseline, and post investigational treatments at Visit 5 and visit 8.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02048644
|Respiratory Medicine Clinical trials Unit|
|Cottingham, East Yorkshire, United Kingdom, HU16 5JQ|
|Principal Investigator:||Simon Hart, MD||Hull University Teaching Hospitals NHS Trust|