Initial Treatment of Patients With Immune Thrombocytopenic Purpura

Initial Treatment of Patients With Immune Thrombocytopenic Purpura: The ITP^2 Study

This study will compare treatment with 3 courses of high-dose dexamethasone versus treatment with prednisone, for patients recently diagnosed with immune thrombocytopenic purpura (ITP). The primary hypothesis is that patients treated with high-dose dexamethasone will obtain a more durable remission than patients treated with prednisone.

ITP is a common disorder associated with significant morbidity. For more than 40 years it has been recognized that this disorder was responsive to corticosteroid therapy. As corticosteroids are easily obtainable and inexpensive, they have become the standard first-line therapy for adult patients with newly-diagnosed ITP. Generally, patients are treated with prednisone at a dose of approximately 1 mg/kg, or 60 mg/day, and once a response is obtained the daily dosage is gradually tapered. While approximately 70% of patients treated in this manner respond initially, most will relapse as the corticosteroid dose is lowered; ultimately only 15-20% of patients achieve a complete or partial remission of their ITP at an "acceptable" dose of prednisone. Recently, several studies have suggested that the use of high dose corticosteroids, specifically pulse dexamethasone, may be a more efficacious initial therapy for ITP, capable of causing a higher initial response rate and a significantly longer duration of remission despite a shorter course of initial therapy.

This study will compare treatment with 3 courses of high-dose dexamethasone versus treatment with prednisone, for patients recently diagnosed with immune thrombocytopenic purpura (ITP). The primary hypothesis is that patients treated with high-dose dexamethasone will obtain a more durable remission than patients treated with standard oral corticosteroids. This may reflect the ability of high dose corticosteroids to eradicate a sensitive pathogenic lymphoid clone that may be transiently susceptible to aggressive immunosuppressive therapy early in the course of disease.

Inclusion Criteria:

• Must meet criteria for a diagnosis of ITP as specified by ASH guidelines
• Must be within 30 days after diagnosis of ITP at the time of randomization (diagnosis of ITP starts with first platelet count ≤ 100,000/μl)
• Platelet count ≤ 30,000/μl at the time ITP is diagnosed, and/or at some time between the diagnosis of ITP and study entry
• Platelet count ≤ 150,000/μl at the time of randomization
• Age ≥ 15 years
• If bone marrow examination is available, it must be compatible with ITP
• Subjects, or their legal guardians, must have the ability to provide informed consent

Exclusion Criteria:

• Rituximab therapy or splenectomy for ITP or for any other cause within the previous 8 weeks.
• Known HIV infection
• Known HCV infection
• Known systemic lupus erythematosus
• Pregnancy or breastfeeding
• Insulin-requiring diabetes mellitus
• Previous exposure to prednisone for ITP at a dose ≥ 1.5 mg/kg prednisone/day for ≥ 1 week prior to study entry
• Ongoing use of treatments that are known to inhibit platelet function, e.g. aspirin
• Anything that in the opinion of the investigator is likely to interfere with participation in the study
• Persons previously randomized in the ITP^2 study
• Persons currently enrolled in other interventional clinical trials
• Exposure to thrombopoietic agent prior to study entry
• Previous exposure to dexamethasone for the treatment of ITP at a dose of 30 mg/day or greater for subjects < 60 kg or 40 mg/day or greater for subjects >= 60 kg for at least four days