Study of Tacrolimus vs Mycophenolate Mofetil in Pediatric Patients With Nephrotic Syndrome

Study Overview
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Brief Summary
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Primary nephrotic syndrome accounts for approximately 90% of the total number of nephrotic syndrome in childhood and it is the most common glomerular disease in children. Although treatment with steroids is uesful for primary nephrotic syndrome, proning to cause frequent relapse/steroid-dependent nephrotic syndrome after treatment, and the usage of immunosuppressive agents has become a new choice for the treatment of such patients. This study is a prospective, randomized, multicenter, open, parallel controlled trial, evaluating the efficacy and safety of steroid combined with the immunosuppressive agents which are tacrolimus and mycophenolate mofetil to children who with frequently relapsing or steroid-dependent nephrotic syndrome, all we wish to obtain the proper drug choice and individualized treatment options for children with nephrotic syndrome.

Detailed Description
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Although steroids are recognized as first-line treatments for nephrotic syndrome, the vast majority of children relapse, and about half of them have frequent relapse or steroids dependence after treatment with steroids alone. Some children experienced steroids-resistance after multiple relapses, and eventually developed into chronic kidney dysfunction. Long-term or repeated application of large doses of steroids will lead to side effects such as obesity, growth retardation, and hypertension. Although the treatment of steroids with immunosuppressive agents is a new choice for the treatment of such patients, traditional immunosuppressive agents such as cyclophosphamide and cyclosporine A will bring some serious irreversible side effects, while immunosuppressive agents tacrolimus has the dual effects of immunosuppression and podocyte protection, and is more widely used in the department of nephrology, what's more, the other immunosuppressive agents mycophenolate mofetil has advantage of no kidney toxic, less adverse reactions and higher safety, which gradually being valued by nephrologists in recent years. This study mainly compares the efficacy and safety of tacrolimus and mycophenolate mofetil in the treatment of children with frequently relapsing or steroids-dependent nephrotic syndrome, in order to provide a more effective and safer treatment for children with nephrotic syndrome as well as the therapeutic medication options.

Official Title
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Study of Tacrolimus vs Mycophenolate Mofetil in Pediatric Patients With Frequently Relapsing or Steroid Dependent Nephrotic Syndrome: a Randomized, Multicenter, Open-label, Parallel-arm Study

Conditions
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Nephrotic Syndrome in Children

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sensitive but frequent relapses or steroids dependence nephrotic syndrome Age: 2 to 18 years old Normal renal function: estimated glomerular filtration rate ≥90ml/min/1.73m2 Morning urine protein <1+ or urine protein-creatinine ratio <0.2g/g (<20 mg/mmol) for 3 consecutive days and above when in enroll No tacrolimus, mycophenolate mofetil, cyclosporine A, rituximab or cyclophosphamide was used within 2 years prior to the enrollment Exclusion Criteria: steroids-resistant nephrotic syndrome Family history of nephrotic syndrome, chronic glomerulonephritis or uremia Leukopenia (White Blood Cells ≤ 3.0 * 10^9 / L) Moderate to severe anemia (hemoglobin <9.0 g/dL) Thrombocytopenia (platelet count <100*10^12/L) Positive Hepatitis B virus serological indicators (Hepatitis B surface antigen or / and Hepatitis B virus e antigen or / and Hepatitis B core antibody), Hepatitis C virus-positive or patients with abnormal liver function (2 or more times of alamine aminotransferase or total bilirubin was exceeded the normal value, and continued to rise for 2 weeks) There are chronic active infections such as Epstein-Barrvirus, cytomegalovirus or Mycobacterium tuberculosis, and the usage of steroids and immunosuppressive agents may aggravate the state of an illness Secondary nephrotic syndrome (such as purpuric nephritis, lupus nephritis, etc.) Those who with hematological or endocrine system diseases as well as serious organs illness such as heart, liver or kidney Those who with other autoimmune diseases or primary immunodeficiencies or tumors Those who was known to be sensitized to tacrolimus, mycophenolate mofetil, glucocorticoids, or any of the above drugs Those who have participated in other clinical trials within three months prior to the enrollment Those who was not suitable for participating this study judged by investigator

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 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: Tacrolimus(Group A)<br>Tacrolimus: 0.5mg and 1mg; Capsule; 0.05-0.10mg/kg/day，BID; Steroid: 5mg; Oral tablets; 1.0-1.5 mg/kg, qod or 0.5-0.75 mg/kg/day, qd; | Drug: Tacrolimus<br>* The patients will be divided into two groups randomly. Tacrolimus dose: 0.05-0.10 mg/kg/day, BID. The concentration for tacrolimus is 5-10 ng/ml，then reduce the dosage of drugs to maintian the concentration for tacrolimus is < 5ng/ml. Total duration : 1 year. Steroid dose: 1.0-1.5 mg/kg, qod or 0.5-0.75 mg/kg/day, qd， then gradually taper the steroid to 5mg/day.<br>* Other names: Tacrolimus capsules（CYONSE®）;|
| Active Comparator: Mycophenolate Mofetil(Group B)<br>Mycophenolate Mofetil: 250mg; Dispersible tablets; 20 30mg/kg/day，BID; Steroid: 5mg; Oral tablets; 1.0-1.5 mg/kg, qod or 0.5-0.75 mg/kg/day, qd; | Drug: Mycophenolate Mofetil<br>* The patients will be divided into two groups randomly. Mycophenolate Mofetil dose: 20 30mg/kg/day，BID. The concentration for MPA-AUC is 30 50 μg.h/ml，then reduce the dosage of drugs to maintian the concentration for MPA-AUC is ≤40 μg.h/ml. Total duration : 1 year. Steroid dose: 1.0-1.5 mg/kg, qod or 0.5-0.75 mg/kg/day, qd， then gradually taper the steroid to 5mg/day.<br>* Other names: Mycophenolate Mofetil Dispersible tablets（CYCOPIN®）;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year relapse-free survival rate | The rate of no relapse within 1 year | 1-year period after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse of nephrotic syndrome during 12 months after randomization | Proportion of patients with one or more relapse(s) of nephrotic syndrome | 1-year period after randomization | 
| Number of relapses during 12 months follow up | Number of nephrotic syndrome relapses per patient year during the 12 months period after randomization | 1-year period after randomization | 
| The first time to relapse | The first time to relapse after patients taking part in this study | 1-year period after randomization | 
| Cumulative prednisone dosage (milligrams per kilogram per year) | The total dosage of prednisones from the beginning to the end of the trial | 1-year period after randomization | 
| Change in serum cholesterol, hemoglobin and blood albumin of the patients | The changes of serum cholesterol, hemoglobin and blood albumin in each follow-up during the study | 1-year period after randomization | 
| Change in renal function of the patients | The change for renal function was judged by the changes of serum creatinine and estimated glomerular filtration rate in each follow-up during the study | 1-year period after randomization | 
| Change in anthropometry and growth velocity during 12-month period after randomization | Changes in standard deviation scores for weight, height and body mass index during 12-month period after randomization | 1-year period after randomization | 
| Adverse event | The number of harmful reactions and the types of adverse events during the study | 1-year period after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nephrotic Syndrome, Frequently Relapsing Nephrotic Syndrome, Steroid Dependent Nephrotic Syndrome, Tacrolimus, Mycophenolate mofetil