To study cardiac and haemodynamic effects of oral Iloprost in patients with secondary pulmonary hypertension due to systemic sclerosis. Dose finding study. Tolerance and safety of oral Iloprost in thee patients with a special attention to acute haemodynamic effects and relevant systemic side effects.

Preliminary assessment of efficacy variable to describe:

• Progression of secondary pulmonary hypertension in systemic sclerosis
• Exercise tolerance and quality of life (EUROQUOL)
• Effect on renal blood flow and other Scleroderma symptoms such as cutaneous lesions and course of microcirculatory examinations and serum markers.

Design and statistics

Here a number of open questions have to be addressed.  Two-armed double-blind randomized placebo-controlled prospective study. 6 or 12 months treatment  in the controlled segment followed by optional open label treatment. Study follow up for all patients over 2 years after enrolment. All patients will receive optimal standay therapy at any time. Study medication will be added to the standard therapy and there will be a blinded (tolerability determined) titration with the comparator group performing a dummy-titration.  Interim assessments will be done when at least 20 of the 40 patients have completed 1/4, 1/2 and one year; the investigators will be kept blinded to the individual patients treatment. The two treatment arms will be compared with descriptive statistics:

Controlled treatment segment over 6-12 months:

• Oral Iloprost 50-150 mg given three times daily
• Placebo using dummy titration

Following the controlled treatment segment all patients can receive an optional open-label treatment with oral Iloprost following the same regimen. Safety and effects assessments for this study end 2 years after enrolment.  Doses will be increased at weekly intervals in steps of 50 mg id. A test dose of 50-100 mg will be applied under catheter observation in the same examination that provides the baseline assessments. The option to increase the dose above 450 mg/day has to be discussed provided there is acceptable tolerability.

Centers and study population

40 patients will be recruited and randomized to receive either oral Iloprost or placebo on top of standard therapy. Up to 3 centers will participate and each center should recruit at least 6 patients. The centers participating will be experienced units of hospitals in the United Kingdom. Patients will have limited Scleroderma with early pulmonary hypertension in the absence of fibrosing alveolitis. The POP should be between 30 and 55 at study entry. They need not have a notable limitation of exercise capacity or renal circulation. Overt cardiac failure is excluded, as well as more severe right heart failure leading to syncopes or hemoptysis.