Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE

Study Overview
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Brief Summary
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Treating severe thrombocytopenia is a challenge in the management of systemic lupus erythematosus. Although rheumatologists have followed some rules in real practice,there is very few evidence to support the current treatment algorithm. The purpose of this study is to compare the complete remission rate and partial remission rate of cyclophosphamide and hydroxychloroquine for treating severe thrombocytopenia in Chinese SLE patients.

Detailed Description
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This is a prospective,randomized,open-label,multi-center clinical trial. The aim of this study is to test the efficacy of GC(gluco-corticosteroid)+HCQ(hydroxychloroquine) and GC(glucocorticosteroid)+CTX(cyclophosphamide) with sequential AZA(azathioprine) in the induction and maintenance therapy of severe thrombocytopenia in SLE patients.

Official Title
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Cyclophosphamide and Hydroxychloroquine for the Treatment of Severe Thrombocytopenia in Systemic Lupus Erythematosus

Conditions
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Thrombocytopenia

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Cyclophosphamide
* Drug: Azathioprine
* Drug: Methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients fulfilled the 1997 ACR modified or SLICC classification criteria of SLE； New onset thrombocytopenia: platelet count <30X109/L(by both routine test and citric acid anti-coagulated blood count test) within 3 months Exclusion Criteria: Thrombocytopenia caused by other reasons, including drugs； Positive for active HAV(hepatitis A virus)/HBV(hepatitis B virus) infection Active HIV(human immunodeficiency virus) or HCV(hepatitis C virus) infection; Active HP(Helicopter pylori) infection; Severe liver and kidney dysfunction； Severe neuropsychiatric lupus； No response to high dose steroid and/or cyclophosphamide 1 month prior to study enrollment； Uncontrolled diabetes or hypertension before entry Active GI bleeding 3 months before entry Intolerant to HCQ in the past treatment history； Severe bone marrow suppression or liver damage caused by cyclophosphamide in the past history； Active infection , including bacteria, virus, fungi, mycobacteria Allergy to any of the study medications Confirmed TTP(thrombolic thrombocytopenic purpura)or CAPS(catastrophic anti-phosphilipid syndrome) Platelet count less than 20X109/L with active bleeding Myelodysplastic diseases Patients with heart and lung function impairment thiopurine S-methyltransferase (TPMT) gene positive -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Active Comparator: Group1:Hydroxychloroquine<br>Hydroxychloroquine: 100 mg tablets by mouth, 400mg everyday for 12 months Methylprednisolone: 4 mg tablets by mouth, 40-50mg everyday and tapering for 12 months | Drug: Hydroxychloroquine<br>* Hydroxychloroquine 200 mg BID for 12 months<br>* Other names: Fenle;Drug: Methylprednisolone<br>* Methylprednisolone 40-50 mg once daily for 1 months and then taped for 12 months<br>* Other names: meizhuole;|
| Active Comparator: Group 2:Cyclophosphamide<br>Cyclophosphamide, Azathioprine & Methylprednisolone Cyclophosphamide: 200mg powder intravenous infusion, 1000mg every month for 6 month. Azathioprine: 100 mg tablets by mouth, everyday for 6 months. Methylprednisolone: 4 mg tablets by mouth, 40-50mg everyday and tapering for 12 months | Drug: Hydroxychloroquine<br>* Hydroxychloroquine 200 mg BID for 12 months<br>* Other names: Fenle;Drug: Cyclophosphamide<br>* Cyclophosphamide 1000mg intravenous infusion every month for 6 months<br>* Other names: Huanlinxianan;Drug: Azathioprine<br>* After Cyclophosphamide treatment, Azathioprine 100mg once daily for 6 months<br>* Other names: liuzuopiaolin;Drug: Methylprednisolone<br>* Methylprednisolone 40-50 mg once daily for 1 months and then taped for 12 months<br>* Other names: meizhuole;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete remission rate | percentage of patients whose platelet count > 100X109/L | at 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| partial remission rate | percentage of patients whose platelet increase to >30X109/L or with at least a two folds increase of the baseline(ie, pretreatment) count and the absence of bleeding | at 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thrombocytopenia, systemic lupus erythematosus, hydroxychloroquine, cyclophosphamide, remission