Bosentan in Digital Ulcers
Condition: Digital Ulcers
MeSH terms: Skin Ulcer; Ulcer
Intervention: Bosentan 62.5 mg; Bosentan 125 mg
Intervention description: Bosentan 62.5-mg oral tablets twice daily (b.i.d.) for 4 weeks (initial dose); Bosentan 125-mg oral tablets administered b.i.d. (target dose)
Intervention MeSH terms: Bosentan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 116.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: digital ulcers; systemic sclerosis; finger ulcers; bosentan; open label

Summary:

      The aim of the study is to collect long-term efficacy, tolerability and safety data of
      bosentan in Systemic Sclerosis (SSc) patients suffering from ischemic digital ulcers (DUs).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with SSc according to the classification criteria of the American College of
             Rheumatology

          2. SSc patients with at least one DU at baseline qualifying as a CU (see definition
             section 3.2.2)

          3. CU occurred < 3 months and > 1 week prior to randomization. The subset of patients
             with SSc felt to be at high risk for DUs will be identified in the screening period
             but will not be eligible for enrollment until a CU has developed

          4. Male or female patients >/= 18 years of age

          5. Women of childbearing potential must have a negative pre-treatment pregnancy test and
             use a reliable method of contraception during study treatment and for at least 3
             months after study treatment termination

          6. Women not of childbearing potential are defined as postmenopausal (i.e., amenorrhea
             for at least 1 year), or surgically or naturally sterile

          7. Signed informed consent.

        Exclusion Criteria:

          1. DUs due to condition other than SSc

          2. Severe PAH (WHO class III and IV)

          3. Systolic blood pressure < 85 mmHg

          4. Hemoglobin concentration < 75% of the lower limit of the normal range

          5. AST and/or ALT values greater than 3 times the upper limit of normal

          6. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C

          7. Severe malabsorption or any severe organ failure (e.g., lung, kidney) or any
             life-threatening condition

          8. Pregnancy or breast-feeding

          9. Previous treatment with bosentan

         10. Treatment with any of the following: glibenclamide (glyburide), fluconazole,
             cyclosporine A, tacrolimus and any other calcineurin inhibitor 1 week prior to
             randomization

         11. Local injection of botulinum toxin in an affected finger 1 month prior to
             randomization

         12. Treatment with parenteral prostanoids (prostaglandin E, epoprostenol, treprostinil
             sodium or other prostacyclin analogs) 3 months prior to randomization

         13. Treatment with inhaled or oral prostanoids one month prior to randomization

         14. Systemic antibiotics to treat infection of DUs 2 weeks prior to randomization

         15. Treatment with phosphodiesterase inhibitors such as sildenafil, except for
             intermittent treatment of male erectile dysfunction

         16. Body weight < 40 kg

         17. Patient with conditions that prevent compliance with the protocol or adhering to
             therapy

         18. Patient who received an investigational product within 1 month preceding screening

         19. Known hypersensitivity to bosentan or any of the excipients.