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Study of Rituximab Monotherapy on Children With New-onset Nephrotic Syndrome: A Randomized Controlled Trial (STORM)

Primary Purpose

Nephrotic Syndrome in Children, Rituximab

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Rituximab
Steroid
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 Rituximab, Glucocorticosteroids

Eligibility Criteria

2 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: New-onset idiopathic nephrotic syndrome Glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry. Exclusion Criteria: Glomerular hematuria: Urine red blood cell counts≥ 10/high power field(HP), ≥ 3 times within 2 weeks; Continuous hypocomplementaemia(< 0.9g/L) ; Repeated or persistent Hypertension(systolic and/or diastolic blood pressures measured greater than the 95th percent of blood pressure in children matching sex, age and height ≥3 different time points) Diagnosis of secondary NS, such as secondary to Systemic Lupus Erythematosus, Immunoglobulin A Vasculitis(IgAV), diabetes, Hepatitis B virus(HBV) infection, etc. Complicated with other kidney diseases, such as multiple renal cysts, ANCA vasculitis, urinary system abnormalities, etc; With a family history of nephrotic syndrome, chronic glomerulonephritis, uremia, or other kidney diseases; Other monogenic genetic diseases known as the effect the condition of nephrotic syndromes, such as Wilms' tumor 1(WT1), NPHS2, LAMB2, PLCE1, etc. Congenital or acquired immunodeficiency, or patients with active tuberculosis, active Epstein-Barr virus and cytomegalovirus(CMV), acute hepatitis B, hepatitis C, HIV infection, deep fungal infection or other active infections. Laboratory indicators were abnormal, such as moderate or severe neutropenia(≤1000/μL), moderate or severe anemia(hemoglobin<9.0g/dL), Thrombocytopenia (platelet count<100* 10^12/L) or with abnormal hepatic function (Alaninetransaminase(ALT), aspartate Aminotransferase(AST) or bilirubin >2.5*upper limit of normal value and continue to increase for 2 weeks); Steroid or immunosuppressive medicine for other diseases within 3 months, such as cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, tripterygium wilfordii, etc. With tumor, severe cardiac failure, severe hepatologic diseases, hematological diseases, or other severe system diseases. Patients who are known to be allergic to rituximab; History of transplantation, excluding cornea or hair transplantation; The attenuated live vaccine was inoculated within 1 month before enrollment; Patients who participated in other clinical trials within three months before enrollment; Patients are not suitable for inclusion in the trial by any investigator.

Sites / Locations

  • Children's Hospital, Zhejiang University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Rituximab Group

Steroid Group

Arm Description

Rituximab dose: 4 doses of 375 mg/m2 rituximab at 1-week intervals( within +7 days).

Daily oral prednisone/prednisolone 2 mg/kg/d (maximum 60 mg/d) for 6 weeks followed by alternate day prednisone/prednisolone, 1.5 mg/kg (maximum of 50 mg), for other 6 weeks.

Outcomes

Primary Outcome Measures

Recurrence-free survival time(day) after first complete remission
The time from complete remission to the first relapse during the whole 52-week follow-up in patients who achieve complete remission within 6 weeks. In order to evaluate the remission, all the participants will document their proteinuria. Relapse is defined by first-morning urine dipstick ≥3+ on three or more consecutive days, 24-h PCR≥2.0g/g, or 24-h urine protein ≥ 50mg/kg, with or without edema after complete remission(KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases). Complete remission is defined by the first morning or 24h PCR ≤ 0.2g/g (or negative or trace dipstick) on three or more consecutive occasions(KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases).

Secondary Outcome Measures

Complete remission of nephrotic syndrome
Complete remission is defined by the first morning or 24h PCR ≤ 0.2g/g (or negative or trace dipstick) on three or more consecutive occasions (KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases). It will be recorded as "1" when patients achieve complete remission, or as "0".
Inefficiency of nephrotic syndrome
Inefficiency is defined as patients still have nephrotic-range proteinuria(first-morning urine dipstick ≥3+dipstick, 24-h PCR≥2.0g/g, or 24-h urine protein ≥ 50mg/kg) after 6-week treatment.
The time(day) to first complete remission
The time(day) from the first medicine administration to complete remission within 6 weeks.Complete remission is defined by the first morning or 24h PCR ≤ 0.2g/g (or negative or trace dipstick) on three or more consecutive occasions (KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases).
Relapse of nephrotic syndrome
Relapse is defined as patients who have first-morning urine dipstick ≥3+ on three or more consecutive days, 24-h PCR≥2.0g/g, or 24-h urine protein ≥ 50mg/kg, with or without edema after complete remission(KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases). It will be recorded as "1" when patients have a relapse, or as "0".
Cumulative prednisone dosage of each individual (milligrams per kilogram per year)
The total dosage of prednisone for each individual from the beginning to the end of the trial.

Full Information

First Posted
November 20, 2022
Last Updated
August 23, 2023
Sponsor
The Children's Hospital of Zhejiang University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT05734794
Brief Title
Study of Rituximab Monotherapy on Children With New-onset Nephrotic Syndrome: A Randomized Controlled Trial
Acronym
STORM
Official Title
Study of Rituximab Monotherapy VS Steroid Therapy on Children With New-onset Nephrotic Syndrome: A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 9, 2023 (Actual)
Primary Completion Date
December 25, 2025 (Anticipated)
Study Completion Date
July 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Children's Hospital of Zhejiang University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
The main objective is to evaluate the effectiveness of Rituximab monotherapy versus steroid therapy on children with new-onset nephrotic syndrome within the 52-week follow-up.
Detailed Description
Nephrotic syndrome(NS) -------the most common glomerular disease in children. Steroid, as the mainstream therapy for decades, many patients suffer from adverse effects of it, such as growth impacted, fat, and glaucoma.There is a urgent need for Steroid-sparing therapy. Rituximab, as a chemical monoclonal antibody against the cluster of differentiation antigen 20(CD20), has proved to be effective in patients with frequent-relapse/steroid-dependent NS. It has also been reported to be effective in six adult patients with new-onset NS. Rituximab mono-therapy in new-onset pediatric NS patients is still unclear.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nephrotic Syndrome in Children, Rituximab
Keywords
Rituximab, Glucocorticosteroids

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rituximab Group
Arm Type
Experimental
Arm Description
Rituximab dose: 4 doses of 375 mg/m2 rituximab at 1-week intervals( within +7 days).
Arm Title
Steroid Group
Arm Type
Active Comparator
Arm Description
Daily oral prednisone/prednisolone 2 mg/kg/d (maximum 60 mg/d) for 6 weeks followed by alternate day prednisone/prednisolone, 1.5 mg/kg (maximum of 50 mg), for other 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Rituximab dose: 4 doses of 375 mg/m2 rituximab at 1-week intervals( within +7 days), associated with trimethoprim-sulfamethoxazole(25-50 mg/kg/day orally twice per day, 3 days per week. If the patient is not allergic) for three months from the first rituximab dosing date(Day 1). Four doses of rituximab are necessary whether the patient achieves complete remission.
Intervention Type
Drug
Intervention Name(s)
Steroid
Intervention Description
Daily oral prednisone/prednisolone 2 mg/kg/d (maximum 60 mg/d) for 6 weeks followed by alternate day prednisone/prednisolone, 1.5 mg/kg (maximum of 50 mg), for other 6 weeks. Vitamin D and calcium(adjusted according to the blood calcium level) were administered for three months.
Primary Outcome Measure Information:
Title
Recurrence-free survival time(day) after first complete remission
Description
The time from complete remission to the first relapse during the whole 52-week follow-up in patients who achieve complete remission within 6 weeks. In order to evaluate the remission, all the participants will document their proteinuria. Relapse is defined by first-morning urine dipstick ≥3+ on three or more consecutive days, 24-h PCR≥2.0g/g, or 24-h urine protein ≥ 50mg/kg, with or without edema after complete remission(KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases). Complete remission is defined by the first morning or 24h PCR ≤ 0.2g/g (or negative or trace dipstick) on three or more consecutive occasions(KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases).
Time Frame
From complete remission to 52 weeks
Secondary Outcome Measure Information:
Title
Complete remission of nephrotic syndrome
Description
Complete remission is defined by the first morning or 24h PCR ≤ 0.2g/g (or negative or trace dipstick) on three or more consecutive occasions (KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases). It will be recorded as "1" when patients achieve complete remission, or as "0".
Time Frame
From admission day to 6 weeks
Title
Inefficiency of nephrotic syndrome
Description
Inefficiency is defined as patients still have nephrotic-range proteinuria(first-morning urine dipstick ≥3+dipstick, 24-h PCR≥2.0g/g, or 24-h urine protein ≥ 50mg/kg) after 6-week treatment.
Time Frame
From admission day to 6 weeks
Title
The time(day) to first complete remission
Description
The time(day) from the first medicine administration to complete remission within 6 weeks.Complete remission is defined by the first morning or 24h PCR ≤ 0.2g/g (or negative or trace dipstick) on three or more consecutive occasions (KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases).
Time Frame
From admission day to 6 weeks
Title
Relapse of nephrotic syndrome
Description
Relapse is defined as patients who have first-morning urine dipstick ≥3+ on three or more consecutive days, 24-h PCR≥2.0g/g, or 24-h urine protein ≥ 50mg/kg, with or without edema after complete remission(KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases). It will be recorded as "1" when patients have a relapse, or as "0".
Time Frame
From admission day to 52 weeks
Title
Cumulative prednisone dosage of each individual (milligrams per kilogram per year)
Description
The total dosage of prednisone for each individual from the beginning to the end of the trial.
Time Frame
From admission day to 52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: New-onset idiopathic nephrotic syndrome Glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry. Exclusion Criteria: Glomerular hematuria: Urine red blood cell counts≥ 10/high power field(HP), ≥ 3 times within 2 weeks; Continuous hypocomplementaemia(< 0.9g/L) ; Repeated or persistent Hypertension(systolic and/or diastolic blood pressures measured greater than the 95th percent of blood pressure in children matching sex, age and height ≥3 different time points) Diagnosis of secondary NS, such as secondary to Systemic Lupus Erythematosus, Immunoglobulin A Vasculitis(IgAV), diabetes, Hepatitis B virus(HBV) infection, etc. Complicated with other kidney diseases, such as multiple renal cysts, ANCA vasculitis, urinary system abnormalities, etc; With a family history of nephrotic syndrome, chronic glomerulonephritis, uremia, or other kidney diseases; Other monogenic genetic diseases known as the effect the condition of nephrotic syndromes, such as Wilms' tumor 1(WT1), NPHS2, LAMB2, PLCE1, etc. Congenital or acquired immunodeficiency, or patients with active tuberculosis, active Epstein-Barr virus and cytomegalovirus(CMV), acute hepatitis B, hepatitis C, HIV infection, deep fungal infection or other active infections. Laboratory indicators were abnormal, such as moderate or severe neutropenia(≤1000/μL), moderate or severe anemia(hemoglobin<9.0g/dL), Thrombocytopenia (platelet count<100* 10^12/L) or with abnormal hepatic function (Alaninetransaminase(ALT), aspartate Aminotransferase(AST) or bilirubin >2.5*upper limit of normal value and continue to increase for 2 weeks); Steroid or immunosuppressive medicine for other diseases within 3 months, such as cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, tripterygium wilfordii, etc. With tumor, severe cardiac failure, severe hepatologic diseases, hematological diseases, or other severe system diseases. Patients who are known to be allergic to rituximab; History of transplantation, excluding cornea or hair transplantation; The attenuated live vaccine was inoculated within 1 month before enrollment; Patients who participated in other clinical trials within three months before enrollment; Patients are not suitable for inclusion in the trial by any investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianhua Mao, PHD.MD
Phone
86057186670015
Email
maojh88@zju.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Fei Liu
Email
alexdevin@163.com
Facility Information:
Facility Name
Children's Hospital, Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Li Qiu-Yu
Phone
17794588355
Email
liqiuyu1992@126.com

12. IPD Sharing Statement

Plan to Share IPD
No
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Study of Rituximab Monotherapy on Children With New-onset Nephrotic Syndrome: A Randomized Controlled Trial

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