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Completed

NCT Number: NCT02048644

Effect of Fostair® on Biomarkers of Platelet Adhesion in Idiopathic Pulmonary Fibrosis

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.

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Key information

Conditions

Idiopathic Pulmonary Fibrosis Lung Diseases Lung Diseases, Interstitial Pulmonary Fibrosis Respiratory Tract Diseases

Age range

40 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Respiratory Medicine Clinical trials Unit

Cottingham, East Yorkshire, HU16 5JQ, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male or female subjects from 40 to 85 years of age
  • Diagnosis of definite IPF according to American Thoracic Society / European respiratory symposium (ATS/ERS) Consensus Statement (2011) using either High-resolution computed tomography (HRCT) or surgical lung biopsy (SLB).
  • Carbon monoxide transfer factor (TLco) of ≥ 30 % predicted ( historical measure accepted as long as within the last year).
  • Able to maintain O2 saturation of ≥ 89% while breathing room air at rest.
  • forced vital capacity (FVC) of 50-80% predicted value
  • Negative serum pregnancy test at screening and negative urine pregnancy test at randomisation for female subjects of childbearing potential.
  • Competency to understand the information given in the Ethics Committee approved Patient Information Sheet and Consent Form; subjects must sign the form prior to the initiation of any study procedures, unless the assessment is performed as standard of care for this disease

Exclusion criteria

  • . Clinically significant respiratory diseases other than IPF, including asbestosis, other pneumoconiosis or hypersensitivity pneumonitis.
  • Clinically significant heart disease defined as a myocardial infarction documented by an ST elevation (STEMI) on electrocardiogram (ECG) within 6 months prior to screening, percutaneous coronary intervention or coronary artery bypass surgery within 6 months prior to screening, unstable angina pectoris, congestive heart failure (NYHA class III/IV or known left ventricular ejection fraction < 25%), ischaemic heart disease, right heart failure, significant right ventricular hypertrophy, or uncontrolled arrhythmia.
  • Current smokers
  • Use of any inhaled long acting beta-agonist or inhaled steroid within the 3 months prior to screening
  • Use of any medication to treat or possibly indicated in the treatment of IPF, such as pirfenidone, and oral corticosteroids.
  • Use of any Antiplatelet therapy which may alter assessment of study end points e.g. clopidogrel, Prasugrel, Dipyridamole etc.
  • History of cancer, precancerous state (eg, familial polyposis, breast cancer 1 (BRCA1),breast cancer 2 (BRCA2), carcinoma in-situ), other than non-melanomatous skin cancer, within 5 years prior to screening.
  • History or evidence of a clinically significant disorder, condition, or disease that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluations, procedures, or completion.
  • Participation in an investigational drug or device trial < 30 days prior to screening

Treatment and study plan

fostair

Drug

beclometasone dipropionate 200mcg and formoterol 12 mcg delivered by inhaler, twice a day for 28 days

Other names: beclometasone dipropionate and formoterol fumarate

Placebo

Drug

placebo matched inhaler 2puffs to be taken twice a day for 28 days

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

Secondary outcomes

  1. 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

  2. sputum eosinophils cells

    Time frame: 1 month

    inflammatory cells will be measured at baseline, and post investigational treatments at Visit 5 and visit 8.

  3. 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.

Sponsors and collaborators

Lead sponsor

Hull University Teaching Hospitals NHS Trust

Other Gov

Collaborators

  • Chiesi Farmaceutici S.p.A.

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Jan 29, 2014
Registry last updated
Jul 15, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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