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

Phase 4TerminatedNCT01861561

Mahidol University43 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Renal Insufficiency Infection

Low-dose intravenous cyclophosphamideDRUG

Intravenous cyclophosphamide 500 mg/m2/dose every 4 weeks/months, total 7 doses

High-dose intravenous cyclophosphamideDRUG

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

Eligibility

Sex: ALLMax age: 15 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: at 6 months of the treatment

Secondary Outcomes

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

Time frame: within 6 months