MMF Versus CYC in the Induction Therapy of Pediatric Active Proliferative LN

Study Overview
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Brief Summary
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A prospective, randomized, multicenter, open-label, parallel-arm Study to compare effectiveness of mycophenolate mofetil versus cyclophosphamide in the Induction Therapy of pediatric patients with Active Proliferative Lupus Nephritis in Chinese population

Detailed Description
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Scattered research in adults showed that both mycophenolate mofetil (MMF) and cyclophosphamide (CYC) can be used in the induction therapy of lupus nephritis. however data is limited in children.Therefore, the purpose of this study is to observe and compare the efficacy and safety of MMF and CYC as induction therapy for children with proliferative lupus nephritis through a multi-center open randomized controlled study.

Official Title
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Mycophenolate Mofetil Versus Cyclophosphamide in the Induction Therapy of Pediatric Patients With Active Proliferative Lupus Nephritis: A Prospective, Randomized, Multicenter, Open-label, Parallel-arm Study

Conditions
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Mycophenolate Mofetil, Cyclophosphamide, Lupus Nephritis

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Mycophenolate Mofetil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Only those who fully meet the following criteria can be considered for inclusion in this study: Age 5-17 years old; SLE patients who meet the updated 2019 eular/acr SLE classification criteria or 2012 SLICC diagnostic criteria; According to the revised International Society of Nephrology / Society of renal pathology (isn/rps) classification in 2018, it conforms to active proliferative ln type III or IV, with or without type V; Glomerular filtration rate EGFR ≥ 60 ml/min/1.73 m2; 24-hour urinary protein quantitation ≥ 25mg/kg, or urinary protein / creatinine 1.0mg/mg; Blood routine WBC count ≥ 3.0*10^9/l, lymphocyte ≥ 0.5*10^9/l before enrollment; No immunosuppressants such as cyclophosphamide, mycophenolate mofetil, cyclosporine A, tacrolimus, azathioprine, methotrexate, or biological agents such as rituximab, baileyoumab, and etaxel were used before enrollment. Exclusion Criteria: A known history of primary immunodeficiency, splenectomy, or any potential disease that makes participants vulnerable to infection; Evidence of hepatitis C, active hepatitis B, HIV infection, tuberculosis infection, severe fungal infection, or other serious infections; Have any history of tumor or cancer; Patients with lupus encephalopathy, diffuse alveolar hemorrhage, severe hemolytic anemia, blood routine platelet count lower than 10.0*10^9/l, glomerular filtration rate eGFR < 60 ml/min/1.73 m2, or patients with other serious complications have unstable vital signs; Have severe gastrointestinal bleeding, pancreatitis, serious heart, liver, blood, endocrine system diseases; Patients who are known to be allergic to mycophenolate mofetil, cyclophosphamide, glucocorticoids or any of the above drugs; Patients who participated in other clinical trials within 3 months before enrollment; The researcher judged that the patient's condition was not suitable for participants in this trial.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 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: Cyclophosphamide<br>Cyclophosphamide for injection, 750mg/m2 each time, 1g at most, once a month for 6 consecutive months. Steroids : intravenous methylprednisolone, 15 30mg/kg · day, maximum 1000mg/day, 3 consecutive days a week for 2 weeks; during the interval of methylprednisolone pulse therapy and after:prednisone tablets 2mg/kg · day with a maximum dose 60mg / day | Drug: Cyclophosphamide<br>* The patients will be divided into two groups randomly. Cyclophosphamide for injection, 750mg/m2 each time, 1g at most, once a month for 6 consecutive months. Steroids : intravenous methylprednisolone, 15 30mg/kg · day, maximum 1000mg/day, 3 consecutive days a week for 2 weeks; during the interval of methylprednisolone pulse therapy and after:prednisone tablets 2mg/kg · day with a maximum dose 60mg / day. The duration of induction therapy: 6 months.<br>|
| Experimental: Mycophenolate mofetil<br>Mycophenolate mofetil, tablets, 30-40mg/ (kg · day), BID, the maximum amount is no more than 2g/d. Steroids : intravenous methylprednisolone, 15 30mg/kg · day, maximum 1000mg/day, 3 consecutive days a week for 2 weeks; during the interval of methylprednisolone pulse therapy and after:prednisone tablets 2mg/kg · day with a maximum dose 60mg / day | Drug: Mycophenolate Mofetil<br>* The patients will be divided into two groups randomly. Mycophenolate mofetil, tablets, 30-40mg/ (kg · day), BID, the maximum amount is no more than 2g/d. Steroids : intravenous methylprednisolone, 15 30mg/kg · day, maximum 1000mg/day, 3 consecutive days a week for 2 weeks; during the interval of methylprednisolone pulse therapy and after:prednisone tablets 2mg/kg · day with a maximum dose 60mg / day. The duration of induction therapy: 6 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effective rate of LN treatment | complete remission and partial remission | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete remission time | complete remission time within 6 months of designed induction therapy | 6 months | 
| Incidence of LN treatment failure | occurrence of end stage renal disease or serum creatinine reached twice the baseline or 24 urinary protein or urinary protein / creatinine reached twice the baseline at 6 months of follow-up. | 6 months | 
| Incidence of creatinine doubling | serum creatinine reaching 2 times of the baseline level | 6 months | 
| LN recurrence rate | (1) proteinuria recurrence, which is defined as continuous proteinuria ≥ 1.0 g/d (or 25mg/kg) after complete remission (CR) or increase ≥ 2.0 g/d (or 50mg/d) after partial remission (PR), with or without hematuria; (2) The increase of Scr level is defined as the increase of Scr level ≥ 50% when the baseline examination is normal, or 30% when the baseline examination is abnormal. | 6 months | 
| SLE recurrence rate | new onset of skin erythema, vasculitis, joint pain, hematological diseases (platelet <50*109/l or hemolytic anemia), neurological symptoms, lupus myocarditis, lupus pneumonia, serous cavity inflammation or new abnormalities in laboratory examination (antibodies, C3 and C4), and SLEDAI score greater than or equal to 4 points. | 6 months | 
| SLE disease activity score | Systemic Lupus Erythematosus Disease Activity Index 2000 score at 6 months | 6 months | 
| partial remission time | Partial remission time within 6 months of designed | 6 months |