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.

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.

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