Prednisone or Dexamethasone in Newly Diagnosed, Previously Untreated Primary Immune Thrombocytopenic Purpura

Study Overview
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Brief Summary
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RATIONALE: Drugs, such as prednisone and dexamethasone, may change the immune system and be an effective treatment for primary immune thrombocytopenic purpura. It is not yet known which drug is more effective in treating primary immune thrombocytopenic purpura. PURPOSE: This randomized phase III trial is studying high-dose dexamethasone to see how well it works compared to standard-dose prednisone in treating patients with newly diagnosed, previously untreated primary immune thrombocytopenic purpura.

Detailed Description
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OBJECTIVES: Primary To evaluate the role of therapy intensification in adult patients with newly diagnosed, previously untreated primary immune thrombocytopenic purpura with high-dose dexamethasone (HD-DXM), in terms of improvement of response at 6 months after initial response, in comparison with standard-doses of prednisone. Secondary Compare rate of initial response. Compare quality of response. Compare rate of final responses and rate of persistent response. Compare rate of bleeding events. Determine rate of resumed response with HD-DXM in non-responder patients or patients who have lost response (arm I only). Compare time to platelet number increase until a hemostatically effective level is reached and/or disappearance of bleeding symptoms. Compare rate of rescue interventions. Compare rate of eligible patients for splenectomy. Compare rate of patients who underwent splenectomy. Compare rate of patients who develop connective tissue diseases or underlying hematological diseases (myelodysplastic syndromes, chronic lymphoproliferative diseases, others). Compare patient's self reported quality of life. OUTLINE: This is a multicenter study. Patients are stratified by treating center. Patients are randomized to 1 of 2 treatment arms. Arm I (Standard-dose prednisone): Patients receive oral prednisone at a standard dose (1 mg/Kg) once daily on days 1-28 followed by a 14-day taper. Patients considered non-responders at day 42 or who have lost response before evaluation of final response (day 180) are crossed to arm II. Arm II (High-dose dexamethasone): Patients receive oral dexamethasone at a high dose (40 mg/day) once daily on days 1-4. Treatment repeats every 14 days for 3 courses. Quality of life is assessed at baseline, on day 42 (arm I) or 46 (arm II) (initial response evaluation day), 180 days after initial response evaluation, and at 3, 9, 12 months after randomization. After completion of study treatment, patients are followed monthly until 1 year after randomization, every 2 months for 1 year, and then every 3 months for 1 year.

Official Title
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Randomized Study of the Treatment of Primary Immune Thrombocytopenic Purpura (ITP) in Newly Diagnosed Untreated Adult Patients. Comparison of Standard Dose Prednisone Versus High-dose Dexamethasone.

Conditions
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Nonneoplastic Condition

Intervention / Treatment
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* Drug: dexamethasone
* Drug: prednisone
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Signed written informed consent according to IGH/EU/GCP and national local laws Newly diagnosed untreated ITP adult patients Age > 18 < 80 years Platelet count <20x109/L Platelet count > 20 x109/L and <50x109/L plus bleeding with score > 8 (according to grading scale at paragraph 7.1) Baseline Quality of Life evaluation questionnaire filled in Newly diagnosed untreated ITP adult patients Age > 18 < 80 years Platelet count <20x109/L Platelet count > 20 x109/L and <50x109/L plus bleeding with score > 8 (according to grading scale at paragraph 7.1) Baseline Quality of Life evaluation questionnaire filled in Exclusion criteria Active malignancy at time of study entry Steroids administration (PDN <1mg/Kg/day) for more than 5 days before randomization Concomitant treatment with anti-platelet and or anti-coagulant drugs Concomitant severe psychiatric disorders Not confirmed diagnosis of ITP for *Positivity of autoimmunity markers: antinucleus (≥1:80), anti-tireoglobulin, anti-tireoperoxidase, anti-cardiolipin (≥ 40 GPL UmL), anti-b2glycoprotein (≥ 40 IgG U/mL) antibodies, Lupus Anticoagulant (KCT ratio, dRVVT ratios ≥1.5 times the upper normal limit ), direct antiglobulin test (DAT ). Presence of autoimmune hemolytic anemia Presence of connective tissue disease Women who are pregnant or breastfeeding Cardiovascular diseases requiring treatment Severe non-controlled, despite therapy, hypertension and diabetes Liver and kidney function impairment (creatinine, ALT, AST >2 times upper normal limit) HCVAb, HIVAb, HBsAg, HBcAb seropositive status Chronic liver disease Documented viral illness by the positivity of IgM, or vaccination both occurred one month before diagnosis Intake of drugs not previously taken within one week before diagnosis Bleeding score 15 due to ICH or to GI bleeding (according to grading scale at paragraph 7.1, Tab. 3) Active gastric ulcer.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARM A - PDN<br>PDN is administered orally at the daily dose of 1 mg/Kg for 4 consecutive weeks (from day 0 to day 28), then, therapy is tapered within 14 days. The patients considered NOT RESPONDER at day 42 or WHO HAVE LOST THE RESPONSE within the evaluation of final response (see paragraph 8.1), will be crossed to ARM B. | Drug: prednisone<br> <br> Procedure: quality-of-life assessment<br> <br> |
| Experimental: ARM B - DXM<br>DXM is administered orally at single fixed daily doses of 40 mg for 4 consecutive days, every 14 days, for 3 consecutive courses. If platelet count is £ 20x109/L or bleeding symptoms related to thrombocytopenia are present, lowdose DXM (0.035 mg/Kg/day) between courses is given. The patients (either from ARM A+B or from ARM B) considered NOT RESPONDER at day 46 or who HAVE LOST THE RESPONSE within the evaluation of final response (see paragraph 8.1), will be considered OFF TREATMENT. For these patients a second line therapy will be considered, according to the medical practice of the Centre (splenectomy or other). | Drug: dexamethasone<br> <br> Procedure: quality-of-life assessment<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final response (complete, partial, and minimal response) rate from evaluation of initial response |  | At day +180 from evaluation of initial response | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial response rate |  | At day 42 (arm I), at day 46 (arm II) | 
| Quality of response per arm |  | At initial evaluation and at final evaluation | 
| Final response rate |  | At day 180 from the statement of initial response | 
| Rate of bleeding events |  | At 3 years from study entry | 
| Resumed response rate in non-responder patients (at day 42) or patients who have lost response before day 180 from the first evaluation (arm I only) |  | At day 42 or before day 180 from the first evaluation | 
| Time to platelet number increase until a hemostatically effective level is reached and/or disappearance of bleeding symptoms |  | At 3 years from study entry | 
| Rate of persistent response |  | At 12 months from the statement of initial response | 
| Association of type of initial response with final and persistent response (in patients with final and persistent response) |  | At 3 years from study entry | 
| Rate of rescue interventions |  | After day 180 from evaluation of initial response | 
| Rate of splenectomy eligible patients |  | At 12 months from enrollment | 
| Rate of patients who have undergone splenectomy during follow-up |  | At 3 years from study entry | 
| Rate of patients who develop connective tissue diseases or underlying hematological diseases (myelodysplastic syndromes, chronic lymphoproliferative diseases, others) during follow-up |  | At 3 years from study entry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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idiopathic thrombocytopenic purpura