Effect of Different Iloprost Doses on Symptoms in Systemic Sclerosis (ILODOSE)

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

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.

Study Overview

• Status: Terminated
• Conditions: Systemic Sclerosis
• Intervention / Treatment: Drug: iloprost low dose; Drug: iloprost therapy up to 2 ng/kg x min; Drug: iloprost

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charrité Universitätsmedizin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; low dose iloprost therapy 0.5 ng/kg x min	Drug: iloprost low dose; 0.5 ng/kg x min over 6 h per day for 21 consecutive days; Other Names: intravenous ilomedin; Drug: iloprost therapy up to 2 ng/kg x min; 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; Other Names: ilomedin treatment
Active Comparator: B; high-dose therapy	Drug: iloprost therapy up to 2 ng/kg x min; 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; Other Names: ilomedin treatment; Drug: iloprost; 0.5-2 ng/kg x min for 6hours a day for 21 consecutive days; Other Names: intravenous ilomedin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Healing of digital ulcers	5 weeks

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Schering-Plough
• Investigators: Principal Investigator: Gabriela Riemekasten, MD, Charite University, Berlin, Germany

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

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Study record dates

Study Major Dates

• Study Start: September 1, 1997
• Primary Completion (Actual): December 1, 2003
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: February 14, 2008
• First Submitted That Met QC Criteria: February 22, 2008
• First Posted (Estimate): February 25, 2008

Study Record Updates

• Last Update Posted (Estimate): February 25, 2008
• Last Update Submitted That Met QC Criteria: February 22, 2008
• Last Verified: December 1, 2007

More Information

Terms related to this study

• Keywords: observational study; systemic sclerosis; randomized; iloprost; digital ulcers
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Vasodilator Agents; Platelet Aggregation Inhibitors; Iloprost
• Other Study ID Numbers: ILO-1998; Schering GmbH