- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02426229
Safety & Suitability of Dabigatran to Inhibit Thrombin in Scleroderma
July 12, 2018 updated by: Medical University of South Carolina
This study evaluates if dabigatran etexilate is safe for use in patients with Scleroderma and Interstitial Lung Disease.
All patients will receive 75mg of dabigatran etexilate twice a day for 6 months.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Skin and pulmonary fibrosis result in substantial morbidity in scleroderma (SSc).
Furthermore, interstitial lung disease (ILD) culminating in pulmonary fibrosis is a major cause of death among scleroderma patients.
Studies implicate the coagulation system, most notably the serine protease thrombin, in the pathogenesis of SSc-ILD.
Thrombin can transform normal lung fibroblasts to a scleroderma fibroblast phenotype.
Dabigatran etexilate is a selective thrombin inhibitor which is FDA-approved for the prevention of thromboembolic complications in patients with atrial fibrillation.
Dabigatran etexilate needs to be studied as a potential anti-fibrotic agent for the treatment of SSc-ILD.
This study is designed to see if dabigatran etexilate is safe for use in patients with scleroderma.
If so, the long term goal of this study is to determine whether or not the fundamental results will translate to a potential clinical intervention for SSc-ILD which can be tested in a future randomized control trial.
Study Type
Interventional
Enrollment (Actual)
15
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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South Carolina
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Charleston, South Carolina, United States, 29425
- Medical University of South Carolina
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age ≥ 18 and ≤ 70 years
- All patients must fulfill the ACR/EULAR criteria for SSc. Patients may have limited (cutaneous thickening distal, but not proximal to elbows and knees, with or without facial involvement) or diffuse (cutaneous thickening proximal to elbows and knees, often involving the chest or abdomen) cutaneous SSc, or systemic sclerosis sine scleroderma
- SSc for less than 7 years, with onset defined as the date of the first non-Raynaud phenomenon manifestation.
- All patients must have interstitial lung disease defined by any ground glass on HRCT and >20% involvement of HRCT by pulmonary fibrosis and/or FVC <70% predicted
Exclusion Criteria:
- Inability to sign consent
- Currently enrolled in another clinical trial
- FVC < 40% predicted and/or DLCO (corrected for hemoglobin) < 30% of predicted (suggesting severe probably irreparable disease)
- Other serious concomitant medical illnesses (e.g., cancer) limiting life expectancy to <1 year at time of enrollment
- FEV1/FVC ratio < 65% (suggesting obstructive disease)
- Clinically significant pulmonary hypertension requiring treatment, based on the clinician's judgment.
- Smoking of cigars, pipes or cigarettes within 3 months prior to and during enrollment
- Clinically significant abnormalities on chest x-ray other than interstitial lung disease (e.g., lung mass, evidence of active pulmonary infection, emphysema)
- Use of prednisone (or equivalent) in doses > 10 mg daily within 3 months prior to and during enrollment
- Use of colchicine, D-penicillamine, cyclophosphamide, mycophenolate mofetil, azathioprine, endothelin receptor antagonists, phosphodiesterase type-5 inhibitors, prostanoids, tyrosine kinase inhibitors, sirolimus, rituximab, perfinidone or other "disease modifying medications" within 3 months prior to and during enrollment
- Pregnancy or lack of use of birth control method in women of childbearing age or lactating
- Liver disease or increased baseline liver enzyme levels (ALT >3 x upper limit of normal)
- Use of CYP450 inhibitors/inducers
- Hemoglobin < 10g/L
- If of child bearing potential, unwillingness to employ a reliable means of contraception (condom, abstinence, IUD, tubal ligation, vasectomy)
- Active infection
- Creatinine clearance <30 ml/min
- Post transplantation
- Active medical and psychiatric conditions which the investigator may consider would interfere with the subject's treatment, assessment, or compliance with the protocol
Anticoagulation-related exclusions include:
- Current anticoagulation therapy with warfarin
- Increased risk of bleeding (e.g., uncorrectable inherited or acquired bleeding disorder)
- Platelet count <100,000/cmm or hematocrit <30% or > 55%
- History of severe gastrointestinal bleeding within 6 months of screening
- Known gastric antral vascular ectasia (GAVE) or gastric/intestinal arterial-venous malformations (AVMs)
- History of CVA within 6 months of screening
- History of risks of falls as judged by the PI
- Surgery or major trauma within the past 30 days
- Any condition that, in the determination of the PI, is likely to require anticoagulation therapy during the study
- Clopidogrel, prasugrel or other anti-platelet therapy within 6 months of screening
- Aspirin therapy >325 mg daily
- Therapy with other thrombin inhibitors
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: dabigatran 75mg
dabigatran etexilate 75mg orally twice daily for 6 months
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dabigatran etexilate 75mg orally twice a day for 6 months
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Composite: Safety of dabigatran patients with scleroderma interstitial lung disease. (complete blood counts, comprehensive metabolic profile, and coagulation studies).
Time Frame: Up to 6 months
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Subjects taking dabigatran will undergo monthly complete blood counts (white blood cell count, hemoglobin, hematocrit, platelet), comprehensive metabolic profile (sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, total bilirubin, AST, ALT, alkaline phosphatase, protein and albumin), and coagulation studies (prothrombin time, partial thromboplastin time and thrombin time).
Women of child-bearing age will be required to have a urine pregnancy test monthly while receiving dabigatran.
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Up to 6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Composite: Preliminary estimate of efficacy of dabigatran in scleroderma. (skin score and dermal fibroblast biology)
Time Frame: Up to 6 months
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We will also include investigations of scleroderma skin (skin score and dermal fibroblast biology) together with studies of scleroderma lung fibroblasts, to obtain preliminary estimates of the effectiveness of dabigatran as a potential disease modifying drug for patients with SSc-ILD.
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Up to 6 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Richard M Silver, MD, Medical University of South Carolina
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2016
Primary Completion (Actual)
June 1, 2018
Study Completion (Actual)
June 21, 2018
Study Registration Dates
First Submitted
March 4, 2015
First Submitted That Met QC Criteria
April 23, 2015
First Posted (Estimate)
April 24, 2015
Study Record Updates
Last Update Posted (Actual)
July 13, 2018
Last Update Submitted That Met QC Criteria
July 12, 2018
Last Verified
July 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Respiratory Tract Diseases
- Connective Tissue Diseases
- Lung Diseases
- Scleroderma, Systemic
- Scleroderma, Diffuse
- Lung Diseases, Interstitial
- Scleroderma, Localized
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protease Inhibitors
- Antithrombins
- Serine Proteinase Inhibitors
- Anticoagulants
- Dabigatran
Other Study ID Numbers
- 1R21AR065089-01A1 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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