Initial Treatment of Patients With Immune Thrombocytopenic Purpura

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Immune Thrombocytopenic Purpura

Intervention / Treatment
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* Drug: Dexamethasone USP Micronized
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose pulse dexamethasone<br> | Drug: Dexamethasone USP Micronized<br>* The dose for dexamethasone is 30 mg/day for patients < 60 kg and 40 mg/day for patients > 60 kg. The patient will be dosed on days 1-4, 15-18 and 29-32. On the remaining days during the treatment phase of the study, the patient will receive placebo capsules.<br>|
| Active Comparator: Standard prednisone therapy<br> | Drug: Prednisone<br>* Prednisone will be administered to study patients at a dose of 60 mg/day for patients less than 60 kg and 80 mg/day for patients > 60 kg for 21 days. The following schedule for tapering of prednisone will be used: after three weeks of treatment at either 60 mg/day (for patients < 60 kg) or 80 mg/day (for patients ≥ 60 kg), the dose will be reduced to 40 mg/day for 1 week, then 20 mg/day for 1 week, then 10 mg/day for 1 week, then 5 mg/day for 1 week and then stopped. Placebo capsules will be added as necessary during the treatment phase of the study, to maintain blinding.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Patients in Each Treatment Arm Who Remain Free of All ITP Therapy With a Platelet Count ≥ 50,000/μl From 60 Days Through 365 Days After Study Entry. |  | From 60 days through 365 days after study entry. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Patients Who Remain Free of All ITP Therapy With a Platelet Count ≥ 150,000/μl From 60 Days Through 365 Days After Study Entry |  | From 60 days through 365 days after study entry | 
| The Percentage of Patients With Platelets ≥ 50,000/μl at 365 Days Who Are Off All Treatment, Have Received ≤ 2 Acute Therapeutic Interventions for Thrombocytopenia, and Whose Last Acute Therapeutic Intervention Occurred at Least 90 Days Before Day 365 |  | 365 days after study entry | 
| The Percentage of Patients Who Remain Free of All ITP Therapy With a Platelet Count of ≥ 150,000 From 180 Through 365 Days After Study Entry |  | From 180 days through 365 days after study entry | 
| The Percentage of Patients Who Remain Free of All ITP Therapy With a Platelet Count of ≥ 50,000 From 180 Through 365 Days After Study Entry |  | From 180 days through 365 days after study entry | 
| The Percentage of Patients Receiving Acute Therapeutic Intervention During the First 60 Days After Study Entry |  | Through 60 days after study entry | 
| The Percentage of Patients Receiving Acute Therapeutic Intervention Beyond the First 60 Days After Study Entry |  | From 60 days through 365 days after study entry | 
| The Percentage of Platelet Counts ≥ 50,000/μl After Day 60 (If a Subject Receives an Acute Therapeutic Intervention, the Next Protocol-specified Platelet Count Will be Excluded From This Analysis, as it May be Influenced by the Intervention.) |  | From 60 days through 365 days after study entry | 
| The Percentage of Platelet Counts ≥ 150,000/μl After Day 60 (If a Subject Receives an Acute Therapeutic Intervention, the Next Protocol-specified Platelet Count Will be Excluded From This Analysis, as it May be Influenced by the Intervention.) |  | From 60 days through 365 days after study entry | 
| The Percentage of Patients Undergoing Splenectomy |  | Through 365 days after study entry | 
| Change in the Quality of Life From Randomization to Weeks 4, 8 and End of Study, Determined Using the SF-36 Health Survey |  | Weeks 4, 8, and 52 after study entry | 
| The Incidence and Severity of Bleeding as Defined by a Customized Bleeding Score |  | Through 365 days after study entry | 
| The Percentage of Patients Not Completing Study Therapy |  | 49 days after study entry | 
| The Percentage of Patients With Severe Adverse Events Attributable to Steroid Therapy |  | Through 1 year after study entry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune thrombocytopenic purpura, ITP, Dexamethasone, Prednisone