Safety & Suitability of Dabigatran to Inhibit Thrombin in Scleroderma

• Status: Completed
• Trial end date: 2018-06-21
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medical University of South Carolina
• Collaborator: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Treatments: Dabigatran; Thrombin

Criteria

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