Effect of Different Iloprost Doses on Symptoms in Systemic Sclerosis

Study Overview
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Brief Summary
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This study compared the efficacy of different dosages of long-term iloprost treatment on Raynaud's phenomenon, ulcer healing, skin thickening, and progression of internal organ sclerosis in systemic sclerosis (SSc). Methods. 50 SSc patients were 1:1 randomised either for maximally tolerated dose up to 2 ng/kg body weight [bw] per minute or low dose (0.5 ng/kg bw per minute) intravenous iloprost administration, for six hours daily over 21 days. The effect on RP, ulcer healing, skin thickness, oesophagus function, lung involvement as assessed by lung function parameters FVC and DLCO, and side effects were measured. Conclusions. The efficacy of prolonged administration of iloprost is also achieved with low dose iloprost by long term treatment. The effects suggest a disease-modifying capability of iloprost, but further studies are needed to proof this hypothesis.

Detailed Description
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50 SSc patients (23 patients with limited SSc; 15 patients with diffuse SSc, and 12 patients with overlap syndromes fulfilling the ACR criteria for systemic sclerosis) and suffering from severe Raynaud's phenomenon were included into the study after written informed consent to participate in this study. Severe Raynaud's phenomenon was defined by a high burden of disease, by trophic skin changes, or the presence of digital ulcers. Patients suffering from SSc related RP and/or digital ulceration were randomized 1 : 1 to one of the following groups that received either high or low dose infusions of iloprost for 21 consecutive days given once or twice a year. High dose patients (n=25) started on 0.5ng per kg bw and min over 6 hours a day. Depending on the tolerability the dosages were increased in increments gradually every two days for 0.5 ng/kg x min. The maximum dose administered was 2.0ng/kg bw and min. Low dose patients (n=25) were permanently treated with 0.5ng/kg bw over 6 hours per day for 21 consecutive days.

Official Title
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Comparision Between Maximally Tolerated Intravenous Iloprost Doses Versus Low-Dosed Iloprost for a 21-Day Treatment Course

Conditions
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Systemic Sclerosis

Intervention / Treatment
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* Drug: iloprost
* Drug: iloprost low dose
* Drug: iloprost therapy up to 2 ng/kg x min


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with secondary Raynaud's phenomenon suffering from severe Raynaud-'s phenomenon with trophical changes or from digital ulcers with written informed consent. Patients had to be stable for their systemic disease and were on stable medication concerning immunosuppression or vasoactive therapies for three months. Exclusion Criteria: Current smokers, patients with a history of gastric ulcers in the last three months, a cardiac ejection fraction below 25%, patients with severe organ involvement or other uncontrolled diseases such as instable angina pectoris, severe anaemia, coagulopathies, azothaemia, cerebral stroke in the last 6 months or malignant diseases were excluded from the study. The last iloprost therapy had to be finished at least 6 months ago. Participation in other studies during the last 4 weeks was also not allowed. For fertile women, a negative pregnancy test was required.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>low dose iloprost therapy 0.5 ng/kg x min | Drug: iloprost low dose<br>* 0.5 ng/kg x min over 6 h per day for 21 consecutive days<br>* Other names: intravenous ilomedin;Drug: iloprost therapy up to 2 ng/kg x min<br>* starting therapy at doses of 0.5 ng/kg x min, increase the dose every two days for 0.5 ng/kg x min up to the maximally tolerated dose or to 2 ng/kg x min<br>* Other names: ilomedin treatment;|
| Active Comparator: B<br>high-dose therapy | Drug: iloprost<br>* 0.5-2 ng/kg x min for 6hours a day for 21 consecutive days<br>* Other names: intravenous ilomedin;Drug: iloprost therapy up to 2 ng/kg x min<br>* starting therapy at doses of 0.5 ng/kg x min, increase the dose every two days for 0.5 ng/kg x min up to the maximally tolerated dose or to 2 ng/kg x min<br>* Other names: ilomedin treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healing of digital ulcers |  | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of RP |  | 6 weeks | 
| Frequency of RP |  | 6 weeks | 
| changes in lung function |  | 4 years | 
| changes in MRSS |  | 6 years | 
| subjective improvement of esophagus function |  | 1 year | 
| subjective benefit from iloprost therapy |  | 1 year | 
| side effecs |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iloprost, systemic sclerosis, digital ulcers, observational study, randomized