Study of Rituximab Monotherapy on Children With New-onset Nephrotic Syndrome: A Randomized Controlled Trial
- Conditions
- Nephrotic Syndrome in ChildrenRituximab
- Interventions
- Drug: Steroid
- Registration Number
- NCT05734794
- Lead Sponsor
- The Children's Hospital of Zhejiang University School of Medicine
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
- New-onset idiopathic nephrotic syndrome
- Glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Steroid Group Steroid 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. Rituximab Group Rituximab Rituximab dose: 4 doses of 375 mg/m2 rituximab at 1-week intervals( within +7 days).
- Primary Outcome Measures
Name Time Method Recurrence-free survival time(day) after first complete remission From complete remission to 52 weeks 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
Name Time Method Complete remission of nephrotic syndrome From admission day to 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). It will be recorded as "1" when patients achieve complete remission, or as "0".
Inefficiency of nephrotic syndrome From admission day to 6 weeks 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.
Relapse of nephrotic syndrome From admission day to 52 weeks 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) From admission day to 52 weeks The total dosage of prednisone for each individual from the beginning to the end of the trial.
The time(day) to first complete remission From admission day to 6 weeks 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).
Trial Locations
- Locations (1)
Children's Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China