Official Title: “Effect of Sildenafil on Digital Ulcers in Systemic Sclerosis”

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.

Study Type: Interventional

Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: November 2004

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(s) in this Clinical Trial

• Drug: Sildenafil therapy
  • oral use

Arms, Groups and Cohorts in this Clinical Trial

• Other: 1, active ulcers
  • sildenafil treatment

Primary Measures

• healing of digital ulcer
  • Time Frame: 6 months
    Safety Issue?: Yes

Secondary Measures

• Decrease of frequency/duration of Raynaud's attacks (monthly)
  • Time Frame: 6 months
    Safety Issue?: Yes
• Prevention of necroses manifestations
  • Time Frame: 6 months
    Safety Issue?: Yes

Inclusion 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Charite University, Berlin, Germany

Overall Clinical Trial Officials and Contacts

Dr. Gabriela Riemekasten, MD Principal Investigator Charité Universitätsklinik Berlin  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00624273

Study ID Number: SDN-D-002G

ClinicalTrials.gov Identifier: NCT00624273

Health Authority: Germany: Ethics Commission

Charité webmail

Skleroderma patient`s organization