A Study to Evaluate the Efficacy of an Oral Medication in the Treatment and Prevention of Digital Ulcers in Patients With Systemic Sclerosis (Scleroderma).

Not Applicable

Completed

Brief Summary: This is a research study of an investigational drug called ambrisentan (Letairis) in the treatment and prevention of digital ulcers in patients with systemic sclerosis.

Detailed Description: Ambrisentan is an endothelin blocker approved for the treatment of pulmonary arterial hypertension. Patients with systemic sclerosis can have damage to their blood vessels, resulting in increased levels of endothelin in their bloodstream that then causes decreased blood flow to the digits. This can result in very painful digital ulcers. We hope to learn whether blocking the action of endothelin with ambrisentan will be helpful in the treatment and prevention of digital ulcers in patients with systemic sclerosis. This therapy is not approved for the treatment of systemic sclerosis, but this study will help us learn whether ambrisentan is safe and effective in the treatment and prevention of digital ulcers in patients with systemic sclerosis.

Recruitment & Eligibility

Inclusion Criteria

Diagnosis of limited or diffuse systemic sclerosis (SSc) according to American College of Rheumatology or LeRoy criteria
Age greater than 18 years of age
At least one digital ulcer located on the volar or lateral surface at or distal to the proximal interphalangeal joints
At least one new DU that developed within 12 weeks prior to screening
Vasodilator therapies, including calcium channel blockers, alpha-1-antagonists, ACE-inhibitors, nitroglycerin, and angiotensin receptor blockers, are permitted as long as the doses are stable for 2 weeks prior to screening and throughout the study
Treatment with omeprazole or other proton pump inhibitors must be stable for 2 weeks prior to screening and throughout the study

Exclusion Criteria

Patients with pulmonary arterial hypertension, NYHA Class III or IV
Patients who are hemodynamically unstable, or have acute renal, cardiac or pulmonary failure
Concurrent malignancy except non-melanoma skin cancers
Patients who have required systemic antibiotics for infected digital ulcers within 2 weeks of screening
Patients receiving phosphodiesterase-5 inhibitors, endothelin receptor antagonists, or prostanoids within 4 weeks of screening
Patients receiving cyclosporine within 6 weeks of screening
Patients who have participated in any investigational study within 30 days of screening
Pregnant or nursing women
Patients with a history of drug or alcohol abuse within 6 months of screening
History of hepatitis B, hepatitis C, or HIV infection
Any medical condition that, in the opinion of the investigator, might interfere with the subject's participation in the study or poses an added risk for the subject
Inability to comply with study and follow-up procedures
Transaminase elevation > 3X the upper limit of normal at screening
Hemoglobin less than 8.5 g/dL
Platelet count less than 100 X 109/L
White blood cell count less than 3.0 X 109/L
Serum creatinine less than 2.0 mg/dL

Arm && Interventions

Group	Intervention	Description
Active	Ambrisentan	Ambrisentan

Primary Outcome Measures

Name	Time	Method
New Digital Ulcers (DU) 4 Weeks Prior to Week 24	4 weeks prior to week 24	The number of new digital ulcers (DU) that have developed in the preceding 4 weeks assessed at week 24 from baseline.

Secondary Outcome Measures

Name	Time	Method
New DU 4 Weeks Prior to Week 12	4 weeks prior to week 12	The number of new DU that have developed in the preceding 4 weeks assessed at week 12 from baseline.
Subjects Experiencing Complete (Total Reepithelialization) Healing of All Baseline DU at Week 12.	12 weeks
Subjects Experiencing Complete Healing of > 50% of the Number of Baseline DU at Week 12.	12 weeks
Change in the Scleroderma Health Assessment Questionnaire (SHAQ) at Week 24 Compared With Baseline.	24 weeks	Range is 0-3 with 0 meaning the least amount of disability and 3 the greatest of disability.