Low-dose VS High-dose IV Cyclophosphamide for Proliferative LN in Children

Study Overview
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Brief Summary
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Proliferative lupus nephritis (LN)is the predominant cause of morbidity and mortality in juvenile Systemic Lupus Erythematosus (SLE). Induction therapy with high-dose intravenous cyclophosphamide can improve renal outcomes, but considerably associated with infection. Although severe infection is the significant complication related to poorer prognosis for juvenile SLE patients in Asia, cyclophosphamide is still commonly used as the drug of choice for severe lupus nephritis. Euro-Lupus Nephritis Trial demonstrated low-dose intravenous cyclophosphamide regimen followed by azathioprine achieved good clinical results comparable with obtained high-dose regimen. There was lower number of severe infection episodes, but no significant difference. Recent studies applied low dose of cyclophosphamide (500 mg/m2/dose or 500 mg/dose)in young patients and showed good renal response. Low-dose intravenous cyclophosphamide regimen might promote non-inferior renal remission whereas decrease risk of serious infection and improve overall patient outcomes.

Official Title
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Efficacy and Infectious Complications of Induction Therapy With Low-dose Versus High-dose Intravenous Cyclophosphamide for Proliferative Lupus Nephritis in Children

Conditions
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Renal Insufficiency, Infection

Intervention / Treatment
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* Drug: Low-dose intravenous cyclophosphamide
* Drug: High-dose intravenous cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Child up to 15 years of age who fulfilled the 1997 updating the American College of Rheumatology revised criteria for the classification of SLE and his or her renal biopsy reveals lupus nephritis class III or IV regarding to International Society of Nephrology/Renal Pathology Society revision on the classification of the lupus nephritis. Exclusion Criteria: patient who has prior renal insufficiency due to chronic kidney disease other than lupus nephritis patient who has the history of cyclophosphamide hypersensitivity patient who has prior cyclophosphamide or mycophenolate mofetil administration within 6 months patient who is pregnant

Ages Eligible for Study
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Maximum 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose intravenous cyclophosphamide<br>Low-dose intravenous cyclophosphamide 500 mg/m2/dose every 4 weeks/months for 7 doses. Total duration is 6 months for the induction treatment. | Drug: Low-dose intravenous cyclophosphamide<br>* Intravenous cyclophosphamide 500 mg/m2/dose every 4 weeks/months, total 7 doses<br>* Other names: Cytoxan;|
| Active Comparator: High-dose intravenous cyclophosphamide<br>High-dose intravenous cyclophosphamide 1,000 mg/m2/dose, the first dose will be started with 500 mg/m2/dose and steped up to 750 mg/m2/dose for the second dose. Then the dosage will be increased to 1,000 mg/m2/dose for the third dose and continued the dosage through the seventh dose. Total duration is 6 months for the induction treatment. | Drug: High-dose intravenous cyclophosphamide<br>* Intravenous cyclophosphamide every 4 weeks/months, total in 7 doses: the 1st dose-500 mg/m2/dose,the 2nd dose-750 mg/m2/dose, the 3rd-7th doses- 1,000 mg/m2/dose with the maximum dose at 1,500 mg/dose<br>* Other names: Cytoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| renal response | 3 main renal parameters: renal function(eCCl),proteinuria(spot urine protein/creatinine ratio, UPCR), and urine sediment (rbc,wbc,and casts) 'renal remission' complete- normal renal function, UPCR<0.2, and normal urine sediment(rbc<5,wbc<5/HPF,and no cast) partial- at least 50%improvement in 2 main parameters with UPCR <= 1.0 and without worsening of remaining main parameter | at 6 months of the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| infection | infectious episode classified in 3 levels mild infection - the infection that is not serious and the patient could be treated with oral antimicrobial agent in outpatient clinic moderate infection - the infection that the patient need admission or intravenous antimicrobial agent serious infection - the infection that the patient is critically ill and need ICU care | within 6 months |