Clinical trial NCT00622687: Effect of Different Iloprost Doses on Symptoms in Systemic Sclerosis
Official title: Comparision Between Maximally Tolerated Intravenous Iloprost Doses Versus Low-Dosed Iloprost for a 21-Day Treatment Course
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Systemic Sclerosis
Keywords: iloprost
systemic sclerosis
digital ulcers
observational study
randomized
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Schering-Plough
First posted: 2008-02-25
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Healing of digital ulcers
timeFrame: 5 weeks
Secondary outcomes:
measure: Duration of RP
timeFrame: 6 weeks
measure: Frequency of RP
timeFrame: 6 weeks
measure: changes in lung function
timeFrame: 4 years
measure: changes in MRSS
timeFrame: 6 years
measure: subjective improvement of esophagus function
timeFrame: 1 year
measure: subjective benefit from iloprost therapy
timeFrame: 1 year
measure: side effecs
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charrité Universitätsmedizin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Gabriela Riemekasten, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Riemekasten G, Jepsen H, Burmester GR, Hiepe F. [Iloprost administration over 21 days as an effective therapy in systemic scleroderma--case report and review of the literature]. Z Rheumatol. 1998 Apr;57(2):118-24. doi: 10.1007/s003930050070. German.
citation: Kawald A, Burmester GR, Huscher D, Sunderkotter C, Riemekasten G. Low versus high-dose iloprost therapy over 21 days in patients with secondary Raynaud's phenomenon and systemic sclerosis: a randomized, open, single-center study. J Rheumatol. 2008 Sep;35(9):1830-7. Epub 2008 Jul 15.