Clinical trial NCT04048161: Study of Tacrolimus vs Mycophenolate Mofetil in Pediatric Patients With Nephrotic Syndrome
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Nephrotic Syndrome in Children
Keywords: Nephrotic Syndrome
Frequently Relapsing Nephrotic Syndrome
Steroid Dependent Nephrotic Syndrome
Tacrolimus
Mycophenolate mofetil
Lead sponsor: The Children's Hospital of Zhejiang University School of Medicine
Sponsor class: OTHER
Collaborators: name: Children's Hospital of Fudan University
name: Peking University First Hospital
name: First Affiliated Hospital of Zhongshan Medical University
name: Nanjing Children's Hospital
name: Chengdu Women and Children's Center Hospital
name: Tongji Hospital
name: Second Xiangya Hospital of Central South University
name: Children's Hospital of Chongqing Medical University
name: Children's Hospital of Soochow University
name: Henan Provincial People's Hospital
name: Shandong Provincial Hospital
First posted: 2019-08-07
Enrollment: 270
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 1-year relapse-free survival rate
timeFrame: 1-year period after randomization
Secondary outcomes:
measure: Relapse of nephrotic syndrome during 12 months after randomization
timeFrame: 1-year period after randomization
measure: Number of relapses during 12 months follow up
timeFrame: 1-year period after randomization
measure: The first time to relapse
timeFrame: 1-year period after randomization
measure: Cumulative prednisone dosage (milligrams per kilogram per year)
timeFrame: 1-year period after randomization
measure: Change in serum cholesterol, hemoglobin and blood albumin of the patients
timeFrame: 1-year period after randomization
measure: Change in renal function of the patients
timeFrame: 1-year period after randomization
measure: Change in anthropometry and growth velocity during 12-month period after randomization
timeFrame: 1-year period after randomization
measure: Adverse event
timeFrame: 1-year period after randomization
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Chongqing
country: China
facility: Children's Hospital of Chongqing Medical University
state: Chongqing
city: Guangzhou
country: China
facility: First Affiliated Hospital of Zhongshan Medical University
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Children's Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
city: Changsha
country: China
facility: Second Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Nanjing Children's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: Children's Hospital of Soochow University
state: Jiangsu
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
city: Chengdu
country: China
facility: Chengdu Women and Children's Center Hospital
state: Shichuan
city: Hangzhou
country: China
facility: The Children Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Children's Hospital, Zhejiang University School of Medicine
name: Jianhua Mao, MD
role: STUDY_CHAIR
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