Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Children's Hospital of Fudan University | OTHER |
| Peking University First Hospital | OTHER |
| First Affiliated Hospital of Zhongshan Medical University | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tacrolimus(Group A) | Experimental | 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; |
|
| Mycophenolate Mofetil(Group B) | Active Comparator | 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; |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tacrolimus | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 1-year relapse-free survival rate | The rate of no relapse within 1 year | 1-year period after randomization |
| 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jianhua Mao, MD | The Children's Hospital of Zhejiang University School of Medicine | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University First Hospital | Beijing | Beijing Municipality | 100032 | China | ||
| Children's Hospital of Chongqing Medical University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23343906 | Result | Ren H, Shen P, Li X, Pan X, Zhang W, Chen N. Tacrolimus versus cyclophosphamide in steroid-dependent or steroid-resistant focal segmental glomerulosclerosis: a randomized controlled trial. Am J Nephrol. 2013;37(1):84-90. doi: 10.1159/000346256. Epub 2013 Jan 22. | |
| 14655180 | Result | Filler G, Young E, Geier P, Carpenter B, Drukker A, Feber J. Is there really an increase in non-minimal change nephrotic syndrome in children? Am J Kidney Dis. 2003 Dec;42(6):1107-13. doi: 10.1053/j.ajkd.2003.08.010. |
Not provided
Not provided
We could not share data without patients' agreement.
Not provided
Not provided
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 10, 2019 | Oct 13, 2023 |
Not provided
| Nanjing Children's Hospital |
| OTHER |
| Chengdu Women and Children's Center Hospital | OTHER |
| Tongji Hospital | OTHER |
| Second Xiangya Hospital of Central South University | OTHER |
| Children's Hospital of Chongqing Medical University | OTHER |
| Children's Hospital of Soochow University | OTHER |
| Henan Provincial People's Hospital | OTHER |
| Shandong Provincial Hospital | OTHER_GOV |
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Mycophenolate Mofetil | Drug | 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. |
|
|
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 |
| Chongqing |
| Chongqing Municipality |
| 401122 |
| China |
| First Affiliated Hospital of Zhongshan Medical University | Guangzhou | Guangdong | 510080 | China |
| Henan Children's Hospital | Zhengzhou | Henan | 451161 | China |
| Tongji Hospital | Wuhan | Hubei | 430030 | China |
| Second Xiangya Hospital of Central South University | Changsha | Hunan | 410011 | China |
| Nanjing Children's Hospital | Nanjing | Jiangsu | 210008 | China |
| Children's Hospital of Soochow University | Suzhou | Jiangsu | 215002 | China |
| Shandong Provincial Hospital | Jinan | Shandong | 250021 | China |
| Children's Hospital of Fudan University | Shanghai | Shanghai Municipality | 201102 | China |
| Chengdu Women and Children's Center Hospital | Chengdu | Shichuan | 610043 | China |
| The Children Hospital of Zhejiang University School of Medicine | Hangzhou | Zhejiang | 310006 | China |
| 12944064 | Result | Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. 2003 Aug 23;362(9384):629-39. doi: 10.1016/S0140-6736(03)14184-0. |
| 17489822 | Result | Wong W. Idiopathic nephrotic syndrome in New Zealand children, demographic, clinical features, initial management and outcome after twelve-month follow-up: results of a three-year national surveillance study. J Paediatr Child Health. 2007 May;43(5):337-41. doi: 10.1111/j.1440-1754.2007.01077.x. |
| 9176846 | Result | Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr. Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children. J Am Soc Nephrol. 1997 May;8(5):769-76. doi: 10.1681/ASN.V85769. |
| 7479966 | Result | Shaw KT, Ho AM, Raghavan A, Kim J, Jain J, Park J, Sharma S, Rao A, Hogan PG. Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells. Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11205-9. doi: 10.1073/pnas.92.24.11205. |
| 16961774 | Result | Koefoed-Nielsen PB, Karamperis N, Hojskov C, Poulsen JH, Jorgensen KA. The calcineurin activity profiles of cyclosporin and tacrolimus are different in stable renal transplant patients. Transpl Int. 2006 Oct;19(10):821-7. doi: 10.1111/j.1432-2277.2006.00359.x. |
| 7911091 | Result | Neidle S, Goodwin GH. A homology-based molecular model of the proline-rich homeodomain protein Prh, from haematopoietic cells. FEBS Lett. 1994 May 30;345(2-3):93-8. doi: 10.1016/0014-5793(94)00446-3. |
| 17989649 | Result | Sepe V, Libetta C, Giuliano MG, Adamo G, Dal Canton A. Mycophenolate mofetil in primary glomerulopathies. Kidney Int. 2008 Jan;73(2):154-62. doi: 10.1038/sj.ki.5002653. Epub 2007 Nov 7. |
| 9469489 | Result | Briggs WA, Choi MJ, Scheel PJ Jr. Successful mycophenolate mofetil treatment of glomerular disease. Am J Kidney Dis. 1998 Feb;31(2):213-7. doi: 10.1053/ajkd.1998.v31.pm9469489. |
| 23813218 | Result | Gellermann J, Weber L, Pape L, Tonshoff B, Hoyer P, Querfeld U; Gesellschaft fur Padiatrische Nephrologie (GPN). Mycophenolate mofetil versus cyclosporin A in children with frequently relapsing nephrotic syndrome. J Am Soc Nephrol. 2013 Oct;24(10):1689-97. doi: 10.1681/ASN.2012121200. Epub 2013 Jun 27. |
| 3588043 | Result | Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am. 1987 Jun;34(3):571-90. doi: 10.1016/s0031-3955(16)36251-4. |
| 40354041 | Derived | Wang J, Liu F, Yan W, Zhou J, Zhang Y, Rong L, Jiang X, Zhao F, Zhu C, Wu X, Li X, Sun S, Wang J, Wang M, Yang Q, Xu H, Chen J, Liu C, Tian M, Feng S, Duan Q, Zhong X, Zhu Y, Li X, Fu H, Huang L, Ma D, Ding J, Ye Q, Mao J. Tacrolimus or Mycophenolate Mofetil for Frequently Relapsing or Steroid-Dependent Nephrotic Syndrome: A Randomized Clinical Trial. JAMA Pediatr. 2025 May 12;179(7):722-9. doi: 10.1001/jamapediatrics.2025.0765. Online ahead of print. |
| 39513526 | Derived | Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6. |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 25, 2023 | Oct 13, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D009404 | Nephrotic Syndrome |
| ID | Term |
|---|---|
| D009401 | Nephrosis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D016559 | Tacrolimus |
| D009173 | Mycophenolic Acid |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
Not provided
Not provided