Phase III Randomized, Double-Blind, Placebo-Controlled Study of Oral Iloprost for Raynaud's Phenomenon Secondary to Systemic Sclerosis

OBJECTIVES:

I. Evaluate the safety and efficacy of oral iloprost, a prostacyclin analog, in patients with Raynaud's phenomenon secondary to systemic sclerosis.

PROTOCOL OUTLINE: This is a randomized, double-blind study. Patients are stratified by participating institution and digital cutaneous ulcers.

Patients receive oral iloprost or placebo twice daily for 6 weeks. Thrombolytic drugs, oral anticoagulants, and heparin are prohibited on study. Concurrent therapy with angiotensin-converting enzyme inhibitors for Raynaud's is prohibited; calcium channel blockers for severe digital ischemia are allowed as needed.

Patients are followed at 2 and 6 weeks.

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Raynaud's phenomenon secondary to systemic sclerosis (SS) SS meets American College of Rheumatology diagnostic criteria
• At least 6 Raynaud's attacks per week

--Prior/Concurrent Therapy--

• No prior participation in oral iloprost study
• At least 4 weeks since participation in other investigational drug studies
• At least 2 months since prostanoid therapy
• At least 12 months since sympathectomy of upper limb
• Ongoing therapy for systemic sclerosis may continue on study Raynaud's therapy discontinued at entry

--Patient Characteristics--

Hematopoietic: No platelet disorder

Hepatic: No bleeding diathesis

Renal: Creatinine clearance (estimated) at least 30 mL/min

Cardiovascular:

No unstable angina pectoris

None of the following within 3 months:

• Stroke
• Transient ischemic attack
• Myocardial infarction

Other:

• No active cancer or other uncontrolled disease
• No current history of alcohol or drug abuse
• No mental disorder precluding compliance
• No pregnant or nursing women
• Negative pregnancy test required of fertile women
• Adequate contraception required of fertile women