Study of Ambrisentan With Antifibrotic Agent Combination Therapy in Diffuse Systemic Sclerosis
Condition: Systemic Sclerosis; Scleroderma
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis
Study type: Interventional

Summary: 
      Systemic sclerosis is a chronic autoimmune connective tissue disorder with no universally
      accepted disease modifying regimen. Recruiting patients for systemic sclerosis treatment
      studies is difficult due to the limited availability of such patients and furthermore the use
      of a placebo arm is often deemed unethical due to the poor survival of diffuse systemic
      sclerosis patients.

      Long-term controlled trials examining functional outcomes and survival from novel therapeutic
      agents for systemic sclerosis are often difficult to undertake because of costs, rarity of
      the disease and ethical issues with the use of a true placebo. Open label single center
      studies while inferior to multicenter placebo controlled studies, have helped establish the
      benefits of certain pharmaceutical agents in systemic sclerosis, and while not universally
      accepted as disease modifying agents, have been used with some success to treat systemic
      sclerosis.

      The hypothesis on which we are basing this study is that an endothelin receptor antagonist
      and disease modifying agent with antifibrotic properties will have additive influence on
      fibrosis, inhibit cellular and humoral hyperactivity and interfere with smooth muscle
      proliferation in the vessel wall. The combination of these two agents will also be the first
      regimen to address the heterogeneity of scleroderma manifestations including ILD, pulmonary
      arterial hypertension and skin manifestations
    

Detailed description: 
      This is an open label, single center study to determine the efficacy and safety of
      ambrisentan and antifibrotic agent combination in systemic sclerosis. Up to twenty patients
      will be recruited within the next year who have early diffuse systemic sclerosis and are
      presently receiving treatment with any of the following antifibrotic agents - cellcept,
      colchicine, azathioprine, D-penicillamine, methotrexate or cyclophosphamide. Ambrisentan will
      be added to the present agent and then followed for 12 months.

      Patients, male or female, > 18 years with a clinical diagnosis of systemic sclerosis
      fulfilling the criteria of the American College of Rheumatology (formerly the American
      Rheumatism Association) classification criteria for systemic sclerosis (24), and diffuse
      cutaneous involvement based on the criteria of LeRoy et al

      A thorough baseline evaluation will determine the extent and severity of systemic sclerosis
      in the individual patients using laboratory studies and the clinical evaluation. Monthly
      follow-ups will capture any safety issues related to the combination therapy based again on
      laboratory studies and clinical evaluation. At the six month and twelve month follow-up a
      thorough evaluation will again be undertaken to evaluate the extent and severity of the
      disorder. Event driven follow-ups will also take place to record and establish any safety
      issues that may arise. Clinical end-points will be the focus of this study.

      Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will
      remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of
      10mg daily on the fourth week. Subjects will continue their present dose and schedule of
      disease modifying/antifibrotic medication for the duration of the study.
    

Intervention name(s): Ambrisentan
Intervention type(s): Drug
Intervention description(s): Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin
Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.
Other intervention name(s): LETAIRIS (ambrisentan) tablets for oral use; Initial U.S. Approval: 2007
Intervention MeSH terms: Ambrisentan
Intervention model: Single Group Assignment
Intervention model description: Single arm open label study.
Masking: None (Open Label)
Primary purpose: Treatment