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Safety & Suitability of Dabigatran to Inhibit Thrombin in Scleroderma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02426229
Recruitment Status : Completed
First Posted : April 24, 2015
Last Update Posted : July 13, 2018
Sponsor:
Collaborator:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Medical University of South Carolina

Tracking Information
First Submitted Date  ICMJE March 4, 2015
First Posted Date  ICMJE April 24, 2015
Last Update Posted Date July 13, 2018
Study Start Date  ICMJE February 2016
Actual Primary Completion Date June 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2015)
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 ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2015)
Composite: Preliminary estimate of efficacy of dabigatran in scleroderma. (skin score and dermal fibroblast biology) [ Time Frame: Up to 6 months ]
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety & Suitability of Dabigatran to Inhibit Thrombin in Scleroderma
Official Title  ICMJE Safety & Suitability of Dabigatran to Inhibit Thrombin in Scleroderma
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Scleroderma
  • Interstitial Lung Disease
Intervention  ICMJE Drug: dabigatran etexilate
dabigatran etexilate 75mg orally twice a day for 6 months
Other Names:
  • Dabigatran
  • Pradaxa
Study Arms  ICMJE Experimental: dabigatran 75mg
dabigatran etexilate 75mg orally twice daily for 6 months
Intervention: Drug: dabigatran etexilate
Publications * Bogatkevich GS, Ludwicka-Bradley A, Silver RM. Dabigatran, a direct thrombin inhibitor, demonstrates antifibrotic effects on lung fibroblasts. Arthritis Rheum. 2009 Nov;60(11):3455-64. doi: 10.1002/art.24935.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 23, 2015)
15
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 21, 2018
Actual Primary Completion Date June 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

    1. Current anticoagulation therapy with warfarin
    2. Increased risk of bleeding (e.g., uncorrectable inherited or acquired bleeding disorder)
    3. Platelet count <100,000/cmm or hematocrit <30% or > 55%
    4. History of severe gastrointestinal bleeding within 6 months of screening
    5. Known gastric antral vascular ectasia (GAVE) or gastric/intestinal arterial-venous malformations (AVMs)
    6. History of CVA within 6 months of screening
    7. History of risks of falls as judged by the PI
    8. Surgery or major trauma within the past 30 days
    9. Any condition that, in the determination of the PI, is likely to require anticoagulation therapy during the study
    10. Clopidogrel, prasugrel or other anti-platelet therapy within 6 months of screening
    11. Aspirin therapy >325 mg daily
    12. Therapy with other thrombin inhibitors
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02426229
Other Study ID Numbers  ICMJE 1R21AR065089-01A1( U.S. NIH Grant/Contract )
1R21AR065089-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Medical University of South Carolina
Study Sponsor  ICMJE Medical University of South Carolina
Collaborators  ICMJE National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators  ICMJE
Principal Investigator: Richard M Silver, MD Medical University of South Carolina
PRS Account Medical University of South Carolina
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP