Sildenafil for Treatment of Digital Ulcers in Patients With Systemic Sclerosis

Study Overview
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Brief Summary
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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
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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: Therapy with iloprost during the last 4 weeks Sympathectomy during the last 4 weeks TIA, stroke, myocardial infarction during the last 6 months Instable angina pectoris Hemorrhagic diathesis, thrombocytic dysfunction, fibromuscular dysplasia Microangiopathic hemolytic anaemia Azotaemia Hypertonus not adjustable with diuretic, clonidine, ACE inhibitors/AT II antagonists, calcium channel blockers) Left ventricular ejection fraction< 20% Hypotonus < 80/40 mm Hg Positive pregnancy test History of cancer History of gastric/duodenic ulcers without endoscopic proof of complete healing Participation in other studies (currently or during the last 4 weeks) Abuse of alcohol or other drugs, smoker 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)

Official Title
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Effect of Sildenafil on Digital Ulcers in Systemic Sclerosis

Conditions
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Active Digital Ulcers

Intervention / Treatment
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* Drug: Sildenafil therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Digital gangrene, ulcers in patients with severe secondary Raynaud's phenomenon 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. Unchanged immunosuppressive therapy 3 months before treatment with sildenafil No effect of prostacyclin treatment, contraindications for prostacyclins, or other reasons excluding this therapy Exclusion Criteria: Therapy with iloprost during the last 4 weeks Sympathectomy during the last 4 weeks TIA, stroke, myocardial infarction during the last 6 months Instable angina pectoris Hemorrhagic diathesis, thrombocytic dysfunction, fibromuscular dysplasia Microangiopathic hemolytic anaemia Azotaemia Hypertonus not adjustable with diuretic, clonidine, ACE inhibitors/AT II antagonists, calcium channel blockers) Left ventricular ejection fraction< 20% Hypotonus < 80/40 mm Hg Positive pregnancy test History of cancer History of gastric/duodenic ulcers without endoscopic proof of complete healing Participation in other studies (currently or during the last 4 weeks) Abuse of alcohol or other drugs, smoker Cardiac failure, use of nitrates

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1, active ulcers<br>sildenafil treatment | Drug: Sildenafil therapy<br>* oral use<br>* Other names: start at 25 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| healing of digital ulcer |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease of frequency/duration of Raynaud's attacks (monthly) |  | 6 months | 
| Prevention of necroses manifestations |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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digital ulcers,, systemic sclerosis,, sildenafil,, vasoactive therapies