Sildenafil for Treatment of Digital Ulcers in Patients With Systemic Sclerosis

Sponsor

Charite University, Berlin, Germany (Other)

Overall Status

Completed

CT.gov ID

NCT00624273

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Active Digital Ulcers	Drug: Sildenafil therapy	Phase 2

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

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

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).

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)

Study Design

Study Type:

Interventional

Actual Enrollment :

17 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effect of Sildenafil on Digital Ulcers in Systemic Sclerosis

Study Start Date :

Feb 1, 2004

Actual Primary Completion Date :

Nov 1, 2004

Actual Study Completion Date :

Feb 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Other: 1, active ulcers sildenafil treatment	Drug: Sildenafil therapy oral use Other Names: start at 25 mg

Arm

Intervention/Treatment

Other: 1, active ulcers

sildenafil treatment

Drug: Sildenafil therapy

oral use

Other Names:

start at 25 mg

Outcome Measures

Primary Outcome Measures

healing of digital ulcer [6 months]

Secondary Outcome Measures

Decrease of frequency/duration of Raynaud's attacks (monthly) [6 months]
Prevention of necroses manifestations [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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