Safety & Suitability of Dabigatran to Inhibit Thrombin in Scleroderma

NCT02426229 | Completed Phase 1 DMC

• 1 other identifier: 1R21AR065089-01A1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Scleroderma; Interstitial Lung Disease

Keywords

SSc; systemic sclerosis; cutaneous systemic sclerosis

Outcome Measures

Primary Outcomes (1)

• Composite: Safety of dabigatran patients with scleroderma interstitial lung disease. (complete blood counts, comprehensive metabolic profile, and coagulation studies).

  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.

  Up to 6 months

Secondary Outcomes (1)

• Composite: Preliminary estimate of efficacy of dabigatran in scleroderma. (skin score and dermal fibroblast biology)

  Up to 6 months

Study Arms (1)

dabigatran 75mg

EXPERIMENTAL

dabigatran etexilate 75mg orally twice daily for 6 months

Drug: dabigatran etexilate

Interventions

dabigatran etexilate DRUG

dabigatran etexilate 75mg orally twice a day for 6 months

Also known as: Dabigatran, Pradaxa

dabigatran 75mg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (2)

• 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.

  PMID: 19877031 BACKGROUND

• Bogatkevich GS, Huggins TJ, Ismail AA, Atanelishvili I, Silver RM. Anti-fibrotic effects of thrombin inhibition in systemic sclerosis-associated interstitial lung disease: Proof of concept. J Scleroderma Relat Disord. 2025 Feb 24:23971983241311625. doi: 10.1177/23971983241311625. Online ahead of print.

  PMID: 40013233 DERIVED

MeSH Terms

Conditions

Scleroderma, Diffuse; Lung Diseases, Interstitial; Scleroderma, Systemic

Interventions

Dabigatran

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Richard M Silver, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2015
• First Posted: April 24, 2015
• Study Start: February 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: June 21, 2018
• Last Updated: July 13, 2018

Record last verified: 2018-07

Locations

US (1)