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

NCT04048161 | Completed Phase 4

• 1 other identifier: STAMP
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 12

Brief Summary

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.

Conditions

Nephrotic Syndrome in Children

Keywords

Nephrotic Syndrome; Frequently Relapsing Nephrotic Syndrome; Steroid Dependent Nephrotic Syndrome; Tacrolimus; Mycophenolate mofetil

Outcome Measures

Primary Outcomes (1)

• 1-year relapse-free survival rate

  The rate of no relapse within 1 year

  1-year period after randomization

Secondary Outcomes (8)

• Relapse of nephrotic syndrome during 12 months after randomization

  1-year period after randomization

• Number of relapses during 12 months follow up

  1-year period after randomization

• The first time to relapse

  1-year period after randomization

• Cumulative prednisone dosage (milligrams per kilogram per year)

  1-year period after randomization

• Change in serum cholesterol, hemoglobin and blood albumin of the patients

  1-year period after randomization

Study Arms (2)

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;

Drug: Tacrolimus

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;

Drug: Mycophenolate Mofetil

Interventions

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.

Also known as: Tacrolimus capsules（CYONSE®）

Tacrolimus(Group A)

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.

Also known as: Mycophenolate Mofetil Dispersible tablets（CYCOPIN®）

Mycophenolate Mofetil(Group B)

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Children's Hospital of Zhejiang University School of Medicine: lead
• Children's Hospital of Fudan University: collaborator
• Peking University First Hospital: collaborator
• First Affiliated Hospital of Zhongshan Medical University: collaborator
• Nanjing Children's Hospital: collaborator
• Chengdu Women and Children's Center Hospital: collaborator
• Tongji Hospital: collaborator
• Second Xiangya Hospital of Central South University: collaborator
• Children's Hospital of Chongqing Medical University: collaborator
• Children's Hospital of Soochow University: collaborator
• Henan Provincial People's Hospital: collaborator
• Shandong Provincial Hospital: collaborator

Study Sites (12)

Peking University First Hospital

Beijing, Beijing Municipality, 100032, China

Location

Children's Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 401122, China

Location

First Affiliated Hospital of Zhongshan Medical University

Guangzhou, Guangdong, 510080, China

Location

Henan Children's Hospital

Zhengzhou, Henan, 451161, China

Location

Tongji Hospital

Wuhan, Hubei, 430030, China

Location

Second Xiangya Hospital of Central South University

Changsha, Hunan, 410011, China

Location

Nanjing Children's Hospital

Nanjing, Jiangsu, 210008, China

Location

Children's Hospital of Soochow University

Suzhou, Jiangsu, 215002, China

Location

Shandong Provincial Hospital

Jinan, Shandong, 250021, China

Location

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

Location

Chengdu Women and Children's Center Hospital

Chengdu, Shichuan, 610043, China

Location

The Children Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310006, China

Location

Related Publications (14)

• 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.

  PMID: 23343906 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.

  PMID: 14655180 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.

  PMID: 12944064 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.

  PMID: 17489822 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.

  PMID: 9176846 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.

  PMID: 7479966 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.

  PMID: 16961774 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.

  PMID: 7911091 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.

  PMID: 17989649 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.

  PMID: 9469489 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.

  PMID: 23813218 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.

  PMID: 3588043 RESULT

• 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.

  PMID: 40354041 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.

  PMID: 39513526 DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome

Interventions

Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Jianhua Mao, MD

  Children's Hospital, Zhejiang University School of Medicine

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: July 30, 2019
• First Posted: August 7, 2019
• Study Start: November 12, 2019
• Primary Completion: May 31, 2023
• Study Completion: July 12, 2023
• Last Updated: October 17, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (12)