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

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.

Study Overview

Status

Completed

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.

Study Type

Interventional

Enrollment (Actual)

270

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Beijing
      • Beijing, Beijing, China, 100032
        • Peking University First Hospital
    • Chongqing
      • Chongqing, Chongqing, China, 401122
        • Children's Hospital of Chongqing Medical University
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • First Affiliated Hospital of Zhongshan Medical University
    • Henan
      • Zhengzhou, Henan, China, 451161
        • Henan Children's Hospital
    • Hubei
      • Wuhan, Hubei, China, 430030
        • Tongji Hospital
    • Hunan
      • Changsha, Hunan, China, 410011
        • Second Xiangya Hospital of Central South University
    • Jiangsu
      • Nanjing, Jiangsu, China, 210008
        • Nanjing Children's Hospital
      • Suzhou, Jiangsu, China, 215002
        • Children's Hospital of Soochow University
    • Shandong
      • Jinan, Shandong, China, 250021
        • Shandong Provincial Hospital
    • Shanghai
      • Shanghai, Shanghai, China, 201102
        • Children's Hospital of Fudan University
    • Shichuan
      • Chengdu, Shichuan, China, 610043
        • Chengdu Women and Children's Center Hospital
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310006
        • The Children Hospital of Zhejiang University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tacrolimus(Group A)
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;

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.

Other Names:
  • Tacrolimus capsules(CYONSE®)
Active Comparator: Mycophenolate Mofetil(Group B)
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;

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.

Other Names:
  • Mycophenolate Mofetil Dispersible tablets(CYCOPIN®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
1-year relapse-free survival rate
Time Frame: 1-year period after randomization
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
Time Frame: 1-year period 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
Time Frame: 1-year period after randomization
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
Time Frame: 1-year period after randomization
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)
Time Frame: 1-year period after randomization
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
Time Frame: 1-year period after randomization
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
Time Frame: 1-year period after randomization
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
Time Frame: 1-year 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
Time Frame: 1-year period after randomization
The number of harmful reactions and the types of adverse events during the study
1-year period after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 12, 2019

Primary Completion (Actual)

May 31, 2023

Study Completion (Actual)

July 12, 2023

Study Registration Dates

First Submitted

July 30, 2019

First Submitted That Met QC Criteria

August 6, 2019

First Posted (Actual)

August 7, 2019

Study Record Updates

Last Update Posted (Actual)

October 17, 2023

Last Update Submitted That Met QC Criteria

October 13, 2023

Last Verified

October 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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