rhTPO Combining Rituximab Versus Low-dose Rituximab in Management of ITP

Study Overview
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Brief Summary
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The project was undertaking by Qilu Hospital of Shandong University and other 13 well-known hospitals in China. In order to report the efficacy and safety of Recombinant Human thrombopoietin combining with Rituximab for the treatment of adults with refractory immune thrombocytopenia (ITP), compared to conventional Rituximab therapy.

Detailed Description
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The investigators are undertaking a parallel group, multicentre, randomised controlled trial of 240 refractory ITP adult patients from 14 medical centers in China. One part of the participants are randomly selected to receive recombinant human thrombopoietin (given subcutaneously at a dose of 300 Units/kg for 14 consecutive days,following with a flexible dosage depending on platelet count until the 29th day), combining with rituximab (given intravenously at a dose of 100 mg weekly for 4 weeks, i.e. Day 1, 8, 15, 22; the others are selected to receive low-dose of rituximab treatment (given intravenously at a dose of 100 mg weekly, i.e. Day 1, 8, 15, 22). Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study. In order to report the efficacy and safety of the combination therapy compared to conventional rituximab therapy for the treatment of adults with refractory ITP.

Official Title
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Recombinant Human Thrombopoietin in Combination With Rituximab Versus Low-dose Rituximab for the Treatment of Refractory ITP.

Conditions
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Purpura, Idiopathic Thrombocytopenic Purpura

Intervention / Treatment
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* Drug: rituximab; recombinant human thrombopoietin (rhTPO)
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the diagnostic criteria for immune thrombocytopenia. Untreated hospitalized patients, may be male or female, between the ages of 18   80 years. To show a platelet count < 30×10^9/L, and with bleeding manifestations. Eastern Cooperative Oncology Group（ECOG）performance status ≤ 2. Willing and able to sign written informed consent Exclusion Criteria: Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 3 months before the screening visit. Received high-dose steroids or [2] intravenous immunoglobulin transfusion(IVIG)in the 3 weeks prior to the start of the study. Current HIV infection or hepatitis B virus or hepatitis C virus infections. Severe medical condition (lung, hepatic or renal disorder) other than ITP. 4.Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure, uncontrolled hypertension or cardiac arrhythmia) 5.Female patients who are nursing or pregnant, who may be pregnant, or who contemplate pregnancy during the study period. 6.Have a known diagnosis of other autoimmune diseases, established in the medical history and laboratory findings with positive results for the determination of antinuclear antibodies, anti-cardiolipin antibodies, lupus anticoagulant or direct Coombs test. 7.Patients who are deemed unsuitable for the study by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 72 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: combination treatment group<br>120 enrolled patients are randomly picked up to take Rituximab in combination with Rh-TPO at the indicated dose. | Drug: rituximab; recombinant human thrombopoietin (rhTPO)<br>* patients in recombination treatment group take Rituximab( intravenously ,100 mg weekly for 4 consecutive weeks); in combination with Rh-TPO( subcutaneously , 300U/kg for 14 consecutive days,followed by flexible treating dosage so as to keep the platelet count above 50×10^9/L until the 29th day)<br>* Other names: Recombinant Human TPO combine with Rituximab;|
| Active Comparator: single treatment group<br>120 enrolled patients are randomly picked up to take Rituximab at the indicated dose. | Drug: Rituximab<br>* patients in recombinant treatment group take Rituximab intravenously at 100 mg weekly for 4 consecutive weeks（Day 1,8,15,22)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of platelet response (Complete Response) | CR. A complete response (CR) was defined as a sustained (≥ 3 months) platelet count ≥ 100×10^9/L | The time frame is up to 3 months per subject | 
| Evaluation of platelet response (Response) | R. A response (R) was defined as a sustained (≥ 3 months) platelet count ≥ 30×10^9/L without recurrence of thrombocytopenia. | The time frame is up to 3 months per subject | 
| Evaluation of platelet response (No Response) | NR.No response (NR) was defined as platelet count < 30 × 10^9/L or a less than two fold increase in platelet count from baseline or the presence of bleeding. Platelet count must be measured on two occasions more than a day apart. | The time frame is up to 3 months per subject | 
| Evaluation of platelet response (relapses) | A relapses was defined as platelet count falls below 30×10^9/L or bleeding accrues after achieving R or CR. | The time frame is up to 3 months per subject | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and frequency of therapy associated adverse events |  | up to 3 months per subject | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Purpura, Idiopathic Thrombocytopenic Purpura