Clinical trial NCT00624273: Sildenafil for Treatment of Digital Ulcers in Patients With Systemic Sclerosis
Official title: Effect of Sildenafil on Digital Ulcers in Systemic Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Active Digital Ulcers
Keywords: digital ulcers,
systemic sclerosis,
sildenafil,
vasoactive therapies
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2008-02-27
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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)

Eligibility criteria: 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

Primary outcomes:
measure: healing of digital ulcer
timeFrame: 6 months
Secondary outcomes:
measure: Decrease of frequency/duration of Raynaud's attacks (monthly)
timeFrame: 6 months
measure: Prevention of necroses manifestations
timeFrame: 6 months
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Riemekasten, PD Dr. med.
Study officials:
affiliation: Charité Universitätsklinik Berlin
name: Dr. Gabriela Riemekasten, MD
role: PRINCIPAL_INVESTIGATOR
References: