Sildenafil for Treatment of Digital Ulcers in Patients With Systemic Sclerosis
Condition: Active Digital Ulcers
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Skin Ulcer; Sclerosis; Ulcer
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a pilot study analyzing the effect of sildenafil therapy on digital ulcers in
      systemic sclerosis. We want to analyze ulcer healing by measuring the size of digital ulcers
      and their count and analyze the effect of sildenafil on angiography.
    

Detailed description: 
      INVESTIGATOR: Dr. Gabriela Riemekasten Anke Praast Prof. G. R. Burmester Prof. Falk Hiepe

      OBJECTIVES:

      Sildenafil is a very potent drug in the treatment of digital ulcers secondary to Raynaud´s
      phenomenon in patients with connective tissue diseases. Probably, sildenafil has a
      disease-modifying capability improving different signs of a disturbed regulation of vascular
      tone in connective tissue diseases. Sildenafil can be used over a long period without
      significant side effects in scleroderma patients and improves disease severity, life quality,
      and prognosis of patients with connective tissue diseases and secondary Raynaud's phenomenon.

      SUBJECTS and CENTERS:

      We want to study 10-15 patients with digital ulcers secondary to connective tissue diseases
      and which are refractory to other drugs, such as calcium channel blockers or iloprost. In
      this pilot study, patients are treated only in the Charité University Hospital.

      INCLUSION/EXCLUSION CRITERIA

      1 . Digital gangrene, ulcers in patients with severe secondary Raynaud's phenomenon

      2. Stable therapy with vasoactive drugs, such as calcium channel blockers, angiotensin
      inhibitors/AT II receptor antagonists or pentoxifyllin 4 weeks before and during the
      treatment with sildenafil.

      3. Unchanged immunosuppressive therapy 3 months before treatment with sildenafil

      4. No effect of prostacyclin treatment, contraindications for prostacyclins, or other reasons
      excluding this therapy

      EXCLUSION CRITERIA:

        1. Therapy with iloprost during the last 4 weeks

        2. Sympathectomy during the last 4 weeks

        3. TIA, stroke, myocardial infarction during the last 6 months

        4. Instable angina pectoris

        5. Hemorrhagic diathesis, thrombocytic dysfunction, fibromuscular dysplasia

        6. Microangiopathic hemolytic anaemia

        7. Azotaemia

        8. Hypertonus not adjustable with diuretic, clonidine, ACE inhibitors/AT II antagonists,
           calcium channel blockers)

        9. Left ventricular ejection fraction< 20%

       10. Hypotonus < 80/40 mm Hg

       11. Positive pregnancy test

       12. History of cancer

       13. History of gastric/duodenic ulcers without endoscopic proof of complete healing

       14. Participation in other studies (currently or during the last 4 weeks)

       15. Abuse of alcohol or other drugs, smoker

       16. Cardiac failure, use of nitrates

      STUDY DESIGN:

      This is an open prospective pilot study of one centre determining the effect of a 6 month
      treatment of sildenafil in patients with acral ulcers in secondary Raynaud's phenomenon due
      to connective tissue diseases.

      Drop out criteria's/ final points:

      1 . Any change of the immunomodulating or suppressing therapy (e.g., treatment with
      cyclophosphamide because of an alveolitis; bolus of steroids > 30 mg/d).

      2. No response on the healing of ulcers after 4 weeks of treatment with sildenafil 3.
      Manifestation of new ulcers/necrosis under sildenafil 4. Escalation of medication with an
      vascular influence (calcium channel blockers, ACE inhibitors/AT II receptor blockers)
    

Intervention name(s): Sildenafil therapy
Intervention type(s): Drug
Intervention description(s): oral use
Other intervention name(s): start at 25 mg
Intervention MeSH terms: Sildenafil Citrate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: digital ulcers,; systemic sclerosis,; sildenafil,; vasoactive therapies