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Nephrotic Syndrome in ChildrenPhase 4STAMPNCT04048161

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

A Phase 4 study testing Tacrolimus and Mycophenolate Mofetil in people with Nephrotic Syndrome in Children, run by The Children's Hospital of Zhejiang University School of Medicine at 12 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 2 to 18 years
Conditions the study is for
Nephrotic Syndrome in Children
What is being tested?
Tacrolimus and Mycophenolate Mofetil
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
270 participants
Where
12 sitesChina
Study dates
12 Nov 2019to 12 Jul 2023
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 13Show fewer
  • 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

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

China12 sites

  • Peking University First Hospital

    Beijing, Beijing Municipality, 100032

  • Second Xiangya Hospital of Central South University

    Changsha, Hunan, 410011

  • Chengdu Women and Children's Center Hospital

    Chengdu, Shichuan, 610043

  • Children's Hospital of Chongqing Medical University

    Chongqing, Chongqing Municipality, 401122

  • First Affiliated Hospital of Zhongshan Medical University

    Guangzhou, Guangdong, 510080

  • The Children Hospital of Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310006

  • Shandong Provincial Hospital

    Jinan, Shandong, 250021

  • Nanjing Children's Hospital

    Nanjing, Jiangsu, 210008

  • Children's Hospital of Fudan University

    Shanghai, Shanghai Municipality, 201102

  • Children's Hospital of Soochow University

    Suzhou, Jiangsu, 215002

  • Tongji Hospital

    Wuhan, Hubei, 430030

  • Henan Children's Hospital

    Zhengzhou, Henan, 451161

Other trials in China

About this study

Official title: 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

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.

Read the detailed description

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.

Keywords
Nephrotic Syndrome, Frequently Relapsing Nephrotic Syndrome, Steroid Dependent Nephrotic Syndrome, Tacrolimus, Mycophenolate mofetil
Medical subject headings
Nephrotic Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TacrolimusDrug

    Also called Tacrolimus capsules（CYONSE®）

    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.

  • Mycophenolate MofetilDrug

    Also called Mycophenolate Mofetil Dispersible tablets（CYCOPIN®）

    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.

Study groups in NCT04048161
Study groupRoleWhat they receive
Tacrolimus(Group A)ExperimentalTacrolimus: 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;
Receives: Drug: Tacrolimus
Mycophenolate Mofetil(Group B)Active comparatorMycophenolate 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;
Receives: Drug: Mycophenolate Mofetil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 1-year relapse-free survival rate

    The rate of no relapse within 1 year

    Measured: 1-year period after randomization

Secondary outcomes (8)

  1. Relapse of nephrotic syndrome during 12 months after randomization

    Proportion of patients with one or more relapse(s) of nephrotic syndrome

    Measured: 1-year period after randomization

  2. Number of relapses during 12 months follow up

    Number of nephrotic syndrome relapses per patient year during the 12 months period after randomization

    Measured: 1-year period after randomization

  3. The first time to relapse

    The first time to relapse after patients taking part in this study

    Measured: 1-year period after randomization

  4. Cumulative prednisone dosage (milligrams per kilogram per year)

    The total dosage of prednisones from the beginning to the end of the trial

    Measured: 1-year period after randomization

  5. 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

    Measured: 1-year period after randomization

  6. 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

    Measured: 1-year period after randomization

  7. 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

    Measured: 1-year period after randomization

  8. Adverse event

    The number of harmful reactions and the types of adverse events during the study

    Measured: 1-year period after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2019
  2. Study start12 Nov 2019
  3. Primary completion31 May 2023
  4. Study completion12 Jul 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
270 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04048161
Sponsor's protocol ID
STAMP
Acronym
STAMP
Status last verified
Oct 2023
First submitted
30 Jul 2019
Last updated
17 Oct 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: We could not share data without patients' agreement.

Publications

  • 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.

    PubMed 23343906

  • 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.

    PubMed 14655180

  • Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. 2003 Aug 23;362(9384):629-39. doi: 10.1016/S0140-6736(03)14184-0.

    PubMed 12944064

  • 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.

    PubMed 17489822

  • 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.

    PubMed 9176846

  • 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.

    PubMed 7479966

  • 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.

    PubMed 16961774

  • 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.

    PubMed 7911091

  • 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.

    PubMed 17989649

  • 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.

    PubMed 9469489

  • 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.

    PubMed 23813218

  • 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.

    PubMed 3588043

  • 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.

    PubMed 40354041

  • 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.

    PubMed 39513526

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Tacrolimus and Mycophenolate Mofetil in people with Nephrotic Syndrome in Children, run by The Children's Hospital of Zhejiang University School of Medicine at 12 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

1-year relapse-free survival rate (time frame: 1-year period after randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04048161, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2023.

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