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

Primary Purpose

Nephrotic Syndrome in Children

Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Tacrolimus
Mycophenolate Mofetil
Sponsored by
The Children's Hospital of Zhejiang University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nephrotic Syndrome in Children focused on measuring Nephrotic Syndrome, Frequently Relapsing Nephrotic Syndrome, Steroid Dependent Nephrotic Syndrome, Tacrolimus, Mycophenolate mofetil

Eligibility Criteria

2 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Tacrolimus(Group A)

Mycophenolate Mofetil(Group B)

Arm Description

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: 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;

Outcomes

Primary Outcome Measures

1-year relapse-free survival rate
The rate of no relapse within 1 year

Secondary Outcome Measures

Relapse of nephrotic syndrome during 12 months after randomization
Proportion of patients with one or more relapse(s) of nephrotic syndrome
Number of relapses during 12 months follow up
Number of nephrotic syndrome relapses per patient year during the 12 months period after randomization
The first time to relapse
The first time to relapse after patients taking part in this study
Cumulative prednisone dosage (milligrams per kilogram per year)
The total dosage of prednisones from the beginning to the end of the trial
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
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
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
Adverse event
The number of harmful reactions and the types of adverse events during the study

Full Information

First Posted
July 30, 2019
Last Updated
October 13, 2023
Sponsor
The Children's Hospital of Zhejiang University School of Medicine
Collaborators
Children's Hospital of Fudan University, Peking University First Hospital, First Affiliated Hospital of Zhongshan Medical University, Nanjing Children's Hospital, Chengdu Women and Children's Center Hospital, Tongji Hospital, Second Xiangya Hospital of Central South University, Children's Hospital of Chongqing Medical University, Children's Hospital of Soochow University, Henan Provincial People's Hospital, Shandong Provincial Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04048161
Brief Title
Study of Tacrolimus vs Mycophenolate Mofetil in Pediatric Patients With Nephrotic Syndrome
Acronym
STAMP
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
November 12, 2019 (Actual)
Primary Completion Date
May 31, 2023 (Actual)
Study Completion Date
July 12, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Children's Hospital of Zhejiang University School of Medicine
Collaborators
Children's Hospital of Fudan University, Peking University First Hospital, First Affiliated Hospital of Zhongshan Medical University, Nanjing Children's Hospital, Chengdu Women and Children's Center Hospital, Tongji Hospital, Second Xiangya Hospital of Central South University, Children's Hospital of Chongqing Medical University, Children's Hospital of Soochow University, Henan Provincial People's Hospital, Shandong Provincial Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nephrotic Syndrome in Children
Keywords
Nephrotic Syndrome, Frequently Relapsing Nephrotic Syndrome, Steroid Dependent Nephrotic Syndrome, Tacrolimus, Mycophenolate mofetil

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
270 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tacrolimus(Group A)
Arm Type
Experimental
Arm Description
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;
Arm Title
Mycophenolate Mofetil(Group B)
Arm Type
Active Comparator
Arm Description
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;
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
Tacrolimus capsules（CYONSE®）
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
Mycophenolate Mofetil Dispersible tablets（CYCOPIN®）
Intervention Description
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.
Primary Outcome Measure Information:
Title
1-year relapse-free survival rate
Description
The rate of no relapse within 1 year
Time Frame
1-year period after randomization
Secondary Outcome Measure Information:
Title
Relapse of nephrotic syndrome during 12 months after randomization
Description
Proportion of patients with one or more relapse(s) of nephrotic syndrome
Time Frame
1-year period after randomization
Title
Number of relapses during 12 months follow up
Description
Number of nephrotic syndrome relapses per patient year during the 12 months period after randomization
Time Frame
1-year period after randomization
Title
The first time to relapse
Description
The first time to relapse after patients taking part in this study
Time Frame
1-year period after randomization
Title
Cumulative prednisone dosage (milligrams per kilogram per year)
Description
The total dosage of prednisones from the beginning to the end of the trial
Time Frame
1-year period after randomization
Title
Change in serum cholesterol, hemoglobin and blood albumin of the patients
Description
The changes of serum cholesterol, hemoglobin and blood albumin in each follow-up during the study
Time Frame
1-year period after randomization
Title
Change in renal function of the patients
Description
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
Time Frame
1-year period after randomization
Title
Change in anthropometry and growth velocity during 12-month period after randomization
Description
Changes in standard deviation scores for weight, height and body mass index during 12-month period after randomization
Time Frame
1-year period after randomization
Title
Adverse event
Description
The number of harmful reactions and the types of adverse events during the study
Time Frame
1-year period after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jianhua Mao, MD
Organizational Affiliation
Children's Hospital, Zhejiang University School of Medicine
Official's Role
Study Chair
Facility Information:
Facility Name
Peking University First Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100032
Country
China
Facility Name
Children's Hospital of Chongqing Medical University
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
401122
Country
China
Facility Name
First Affiliated Hospital of Zhongshan Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Facility Name
Henan Children's Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
451161
Country
China
Facility Name
Tongji Hospital
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
Facility Name
Second Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410011
Country
China
Facility Name
Nanjing Children's Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210008
Country
China
Facility Name
Children's Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215002
Country
China
Facility Name
Shandong Provincial Hospital
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250021
Country
China
Facility Name
Children's Hospital of Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
201102
Country
China
Facility Name
Chengdu Women and Children's Center Hospital
City
Chengdu
State/Province
Shichuan
ZIP/Postal Code
610043
Country
China
Facility Name
The Children Hospital of Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310006
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
We could not share data without patients' agreement.
Citations:
PubMed Identifier
23343906
Citation
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Results Reference
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Citation
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Citation
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Study of Tacrolimus vs Mycophenolate Mofetil in Pediatric Patients With Nephrotic Syndrome

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