A randomised controlled trial of Dabigatran Etexilate on airway inflammation and coagulation in severe corticosteroid dependent asthma.
- Conditions
- 10006436severe asthmaSevere refractory asthma
- Registration Number
- NL-OMON39442
- Lead Sponsor
- Academisch Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 36
• Age >= 18 years
• Non-smoking patients, or patients who stopped smoking more than 12 months ago and KCO >= 90% pred.
• Able to give written and dated informed consent prior to any study-specific procedures
• All patients have previous evidence of variable airways obstruction within the last 5 yrs, as documented by at least one of the following:
*- Reversibility in forced expiratory volume in one second (FEV1) of >=9% predicted after 4 puffs of
a 100 µg salbutamol dose-aerosol, administered via a spacer.
*- A mean diurnal variation in peak expiratory flow (PEF) >=15% (highest PEF*lowest PEF) per
mean PEF on >=4 days per week for a minimum of 2 weeks.
*- An increase in FEV1 of >=400 mL after a course of prednisolone 0.5 mg•kg*1•day*1 for 14
days.
*- A provocative concentration causing a 20% fall in FEV1 with histamine or methacholine <8
mg/mL.
• On stable doses of oral and inhaled corticosteroids during the previous 4 weeks and during the study.
• No other clinically significant abnormality on history and clinical examination
• Severe asthma according to the criteria of the International Consensus of the Innovative Medicine Initiative (IMI)
• High- and ultrahigh dose of ICS (Fluticasone >=1000 µg/day or equivalent drug) with continuous use of oral corticosteroids (>=5 mg/day).
• Sputum eosinophil count > 3% of the total cell count.
• Women who are pregnant or lactating or who have a positive urine pregnancy test at screening
• Ongoing use of tobacco products of any kind.
• Ex-smoking patients with reduced diffusion capacity: KCO < 90% pred.
• Use of omalizumab during the last 6 months before randomization
• Use of heparin, LMWH, NSAID or vitamin K antagonists.
• Any bleeding diathesis
• History of acute intracranial disease or haemorrhagic stroke
• Major surgery, trauma, uncontrolled hypertension, or myocardial infarction in the past 3 months
• Gastrointestinal or urogenital bleeding, or ulcer disease in the past 6 months
• Severe liver disease
• Alanine or aspartate aminotransferase concentrations greater than two times the upper limit of
the normal range in the past month
• Severe renal insufficiency (creatinine clearance less than 30 mL/min)
• Active malignant disease
• Participation in any clinical investigational drug treatment protocol within the preceding 30 days
• Unwillingness or inability to comply with the study protocol for any other reason
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint will be the change from baseline in percentage of eosinophils<br /><br>in induced sputum as a marker of anti-inflammatory activity after 3 months<br /><br>treatment with dabigatran etexilate. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints will be changes from baseline in asthma control, lung<br /><br>function, exhaled nitric oxide, and changes in markers of hemostasis and<br /><br>inflammation in blood and induced sputum.</p><br>