Combined Steroid and Cyclosporin as First-line Treatment in Adults With Primary Immune Thrombocytopenia

Study Overview
=================
Brief Summary
-----------------
Randomized, open-label, multicenter study to compare the efficacy and safety of cyclosporin plus standard steroid compared to standard steroid monotherapy for the first-line treatment of adults with primary immune thrombocytopenia (ITP).

Detailed Description
-----------------
The investigators are undertaking a parallel group, multicenter, randomized controlled trial of 253 adults with ITP in China. Patients were randomized to cyclosporin plus standard steroid compared to standard steroid monotherapy group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study.

Official Title
-----------------
A Multicenter Randomized Trial of First Line Treatment for Newly Diagnosed Immune Thrombocytopenia: Standard Steroid Treatment Versus Combined Steroid and Cyclosporin

Conditions
-----------------
Immune Thrombocytopenia

Intervention / Treatment
-----------------
* Drug: Cyclosporine Oral Product
* Drug: Prednisone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Newly-diagnosed, treatment-naive primary ITP; Platelet counts <30×10^9/L; Platelet counts < 50×10^9/L and significant bleeding symptoms (WHO bleeding scale 2 or above); Willing and able to sign written informed consent. Exclusion Criteria: Pregnant or lactating women; Secondary ITP (have a known diagnosis of connective tissue diseases, malignancy, active infection, HIV infections or hepatitis B virus or hepatitis C virus infections); Received first-line and second-line ITP specific treatments (e.g., steroids, intravenous immunoglobulin, TPO-RAs, rhTPO, rituximab, etc); Received drugs affecting the platelet counts within 6 months before the screening visit (e.g., chemotherapy, anticoagulants, etc); Severe medical condition (lung, heart, hepatic or renal disorder); Patients who are deemed unsuitable for the study by the investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclosporin plus Steroid<br>Cyclosporin: started orally 1 mg/kg/d in two divided doses for 1 week, increased to 1.5 mg/kg/d for 1week, further increased to 2.5 mg/kg/d and then continued for 24 weeks. After 26 weeks of cyclosporin treatment, the dose for patients who achieved complete response was reduced by 25 mg/d every 2 weeks to ensure continuing the lowest dose that achieved the targeted serum level of cyclosporin and a safe platelet count. Standard regimen of steroid for a total of 10 weeks: 1 mg per kilogram of body weight for 2 weeks followed by 40 mg daily for 2 weeks, 20 mg daily for 2 weeks, 10 mg daily for 2 weeks, 5 mg daily for 1 week and 5 mg every other day for the final week. | Drug: Cyclosporine Oral Product<br>* A combination of cyclosporin with standard steroid in newly diagnosed ITP patients: cyclosporin was started orally 1 mg/kg/d in two divided doses for 1 week, increased to 1.5 mg/kg/d for 1week, further increased to 2.5 mg/kg/d and then continued for 24 weeks. The therapeutic serum level of cyclosporin was 75 to 150 ug/L. After 26 weeks of cyclosporin treatment, the dose for patients who achieved complete response was reduced by 25 mg/d every 2 weeks to ensure continuing the lowest dose that achieved the targeted serum level of cyclosporin and a safe platelet count; standard steroid regimen included orally prednisone for a total of 10 weeks: 1 mg per kilogram of body weight for 2 weeks followed by 40 mg daily for 2 weeks, 20 mg daily for 2 weeks, 10 mg daily for 2 weeks, 5 mg daily for 1 week and 5 mg every other day for the final week.<br>* Other names: Prednisone;Drug: Prednisone<br>* Standard steroid in newly diagnosed ITP patients: orally prednisone for a total of 10 weeks: 1 mg per kilogram of body weight for 2 weeks followed by 40 mg daily for 2 weeks, 20 mg daily for 2 weeks, 10 mg daily for 2 weeks, 5 mg daily for 1 week and 5 mg every other day for the final week.<br>|
| Active Comparator: Standard steroid<br>Standard regimen for a total of 10 weeks: 1 mg per kilogram of body weight for 2 weeks followed by 40 mg daily for 2 weeks, 20 mg daily for 2 weeks, 10 mg daily for 2 weeks, 5 mg daily for 1 week and 5 mg every other day for the final week. | Drug: Prednisone<br>* Standard steroid in newly diagnosed ITP patients: orally prednisone for a total of 10 weeks: 1 mg per kilogram of body weight for 2 weeks followed by 40 mg daily for 2 weeks, 20 mg daily for 2 weeks, 10 mg daily for 2 weeks, 5 mg daily for 1 week and 5 mg every other day for the final week.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment failure | Nonresponse or loss of response for those who had achieved overall response (assessed in a time-to-event analysis). Overall response was defined as platelet count ≥ 30,000 per cubic millimeter and at least 2-fold increase of the baseline count and absence of bleeding. | From date of randomization until 2 years or the end of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with side effects | Number of patients with Medication adverse events. | From date of randomization until 2 years or the end of follow-up | 
| Number of patients with bleeding | Number of patients with bleeding complication (WHO bleeding score) | From date of randomization until 2 years or the end of follow-up | 
| Sustained response | The maintenance of platelet count ≥ 30 x 10^9/L, at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 6-month follow-up. | From date of randomization until 2 years or the end of follow-up | 
| Overall response (OR) | Platelet count ≥ 30,000 per cubic millimeter and at least 2-fold increase of the baseline count and absence of bleeding. | From date of randomization until 2 years or the end of follow-up | 
| Complete response (CR) | Platelet count > 100,000 per cubic millimeter and absence of bleeding. | From date of randomization until 2 years or the end of follow-up | 
| Time to response | The time from starting treatment to time of achievement of CR or OR | From date of randomization until 2 years or the end of follow-up | 
| Duration of response | time from OR until loss of response or until the last follow-up visit | From date of randomization until 2 years or the end of follow-up | 
| Remission | a durable platelet count ≥30×10^9/L without bleeding up to 12 months from randomization. | at 12-month follow-up | 
| Rescue therapy | any new medical intervention taken to increase the platelet count or prevent bleeding events or an increase in the dose of concomitant treatments | From date of randomization until 2 years or the end of follow-up | 
| Associated factors of treatment failure, OR, SR and remission | Factors that are associated with treatment failure, OR, SR and remission | From date of randomization until 2 years or the end of follow-up |