The Coagulation Cascade in Idiopathic Pulmonary Fibrosis

Not Applicable

• Conditions: Idiopathic Pulmonary Fibrosis; Interstitial Lung Disease; IPF
• Interventions: Drug: Dabigatran; Radiation: FDG PET scan

• Registration Number: NCT02885961
• Lead Sponsor: University College, London

Brief Summary

The pathogenesis of idiopathic pulmonary fibrosis (IPF) is incompletely understood but recurrent epithelial injury occurs which evokes the coagulation cascade. Thrombin is produced as a result and is over expressed in IPF patients, so may be important in propagating disease activity. We aim to recruit patients with IPF and then complete FDG (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose) PET (positron emission tomography) scans pre and post manipulation of the coagulation cascade to assess the role of this biological pathway in disease activity. Previous studies from our institution have demonstrated increased FDG avidity in the lungs of patients with IPF (assessed using FDG PET scans) but to date the cells and pathways responsible for this signal have not been identified and thus need further exploration.

Detailed Description

Patients with IPF who meet all the inclusion criteria (and none of the exclusion criteria) will be assessed and invite to participate.

They will undergo baseline assessment with lung function, 6 minute walk test and health quality assessments.

Blood tests will assess the pro-coagulant state of these individuals. They will undergo a baseline FDG PET scan followed by manipulation of the coagulation cascade with 24 days (+/- 3 days) dabigatran. They will then complete a second FDG PET, health quality assessments and blood tests to demonstrate target engagement.

Study Timeline

• Status Verified: 2016-08
• Study Start: 2016-08
• Study First Submitted: 2016-08-15
• Study First Submitted QC: 2016-08-26
• Last Update Submitted: 2016-08-26
• Study First Posted: 2016-09-01
• Last Update Posted: 2016-09-01
• Primary Completion: 2017-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• A diagnosis of IPF based on multi disciplinary meeting discussion following review of the clinical history, characteristic features on HRCT (high resolution CT scan) and/or usual interstitial pneumonia (UIP) histology.
• Written informed consent obtained from subject.

Exclusion Criteria

• Age <40 or >80 years
• Renal impairment as defined by a creatinine clearance of <30 millilitres/min
• Significant liver impairment with evidence of synthetic dysfunction
• Any contraindication to anti-coagulation including previous life threatening or serious bleed or bleeding tendency.
• Co-administration of any concomitant medications prohibited in full protocol. N-acetyl cysteine, prednisolone up to 10mg daily and pirfenidone are permitted.
• Pregnant, breast feeding or unwilling to practice birth control during participation in the study (females of child bearing age).
• Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the patient of the quality of the data.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dabigatran	Dabigatran	All patients will be entered into the arm, i.e. this is a single arm study. All patients will complete 2 FDG PET scans. All patients will receive dabigatran (direct thrombin inhibitor) at a dose of 110mg twice daily (oral). The drug will be given for 24 days (+/-3 days). The variation in duration reflects that scans are completed Monday to Friday only.
Dabigatran	FDG PET scan	All patients will be entered into the arm, i.e. this is a single arm study. All patients will complete 2 FDG PET scans. All patients will receive dabigatran (direct thrombin inhibitor) at a dose of 110mg twice daily (oral). The drug will be given for 24 days (+/-3 days). The variation in duration reflects that scans are completed Monday to Friday only.

Primary Outcome Measures

Name	Time	Method
Demonstrate a change in FDG (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose) avidity	Approximately 4 weeks	FDG avidity describes the degree of tissue uptake of the labelled glucose. It is a numerical continuous variable. It is calculated from the scan using several methods, manually on a workstation and using a mathematical modelling computer programme. The main number generated is called the standardised uptake value (SUV) and the higher the number the higher the metabolic activity in the area. The degree of activity will be quantified for each individual and compared with standard measures of disease activity i.e. lung function measures and quality of life questionnaires. For each individual the change in the SUV measure will be analysed from the scan performed before and then after manipulation of the coagulation cascade.

Secondary Outcome Measures

Name	Time	Method
Demonstrate changes in various coagulation factors	Approximately 4 weeks	This patient group have demonstrated a hyper coagulable state in a number of previous studies. We will demonstrate this using blood tests prior to administration of dabigatran. The coagulation markers (a blood test, many used in standard clinical practice) will be repeated during treatment to demonstrate target engagement.