NCT02048644

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

Completed Phase 2 Last updated 11 July 2019

What this trial tests

Phase 2 trial testing fostair in Idiopathic Pulmonary Fibrosis in 20 participants. Completed in 1 May 2015.

Timeline

1 March 2014

Primary endpoint
1 April 2015

1 May 2015

Quick facts

Lead sponsor	Hull University Teaching Hospitals NHS Trust
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	treatment
Enrollment	20
Start date	1 March 2014
Primary completion	1 April 2015
Estimated completion	1 May 2015
Sites	1 location across United Kingdom

Drugs / interventions tested

• fostair — full drug profile →
• placebo

Conditions studied

• Idiopathic Pulmonary Fibrosis — all drugs for Idiopathic Pulmonary Fibrosis →

Sponsor

Hull University Teaching Hospitals NHS Trust

Who can join

Adults 40 to 85, any sex, with Idiopathic Pulmonary Fibrosis. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 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.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.