Minimal Change Disease
Conditions
Brief summary
To evaluate the safety and efficacy of ripertamab and its combination with tacrolimus in the initial treatment of MCD to provide a treatment regimen with higher remission rates, lower recurrence rates, and fewer side effects in patients with MCD.
Detailed description
Minimal change disease is the third most common primary kidney disease in adults with idiopathic nephrotic syndrome. The pathological features of the disease are no or only slight changes under light microscope, and the foot process fusion under electron microscope. The KDIGO guidelines recommend oral adequate doses of glucocorticoids as the initial treatment for adults with MCD. However, 48%-76% of patients relapse after tapering or gradual discontinuation of the drug, requiring a high cumulative dose of glucocorticoids. As the cumulative dose of glucocorticoids increases, the potential for side effects increases. In addition, 10% to 30% of patients frequently relapse, and 15% to 30% of these are steroid dependent. Therefore, the clinical goals for patients with MCD are to achieve early remission of proteinuria, reduce hormonal side effects, and more importantly, prevent the recurrence of proteinuria.
Interventions
DRUGSupportive care+Prednisone
Supportive care: Control blood pressure:ACEI/ARB; Diet that is low in fat and salt; Stop smoking; Moderate exercise. Induction period: 1mg/kg/day. The maximum dose is not more than 60mg. The duration of adequate prednisone is a minimum of 4 weeks and a maximum of 16 weeks. Maintenance period: A reduction of 5-10mg/wk was initiated after 2 weeks of complete remission and finally discontinued after 6 months of maintenance at 5mg/day.
DRUGSupportive care+Tacrolimus+Ripertamab
Supportive care: Control blood pressure:ACEI/ARB; Diet that is low in fat and salt; Stop smoking; Moderate exercise. Tacrolimus：Induction period: 0.05mg/kg/d. It will be given in two doses 12 hours apart. The blood concentration should be up to 5-10ng/ml. Maintenance therapy was initiated two weeks after complete remission; Maintenance period: Reduced to a blood concentration of 3-8ng/ml, and stopped after 6 months of maintenance treatment. Ripertamab: Given twice every two weeks at a dose of 1000mg. 1000mg is added at 6 months.
DRUGSupportive care+Ripertamab
Supportive care: Control blood pressure:ACEI/ARB; Diet that is low in fat and salt; Stop smoking; Moderate exercise. Ripertamab: Given twice every two weeks at a dose of 1000mg. 1000mg is added at 6 months.
Sponsors
First Affiliated Hospital Xi'an Jiaotong University
Second Affiliated Hospital of Xi'an Jiaotong University
The Second Affiliated Hospital of Air Force Military Medical University
Shaanxi Provincial People's Hospital
Shaanxi Provincial Hospital of Chinese Medicine
Air Force Military Medical University, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-80 years old; 2. Primary minimal change disease confirmed by renal biopsy (Initial therapy); 3. 24h-UTP\>3.5g/d or PCR\>3500mg/g, and serum albumin\<30g/L; 4. Agree to participate in the project and sign the informed consent.
Exclusion criteria
1. Secondary minimal change disease; 2. eGFR\<60 mL/min/1.73m2; 3. Had history of mental disease, dysnoesia, serious cardiovascular and cerebrovascular diseases, pulmonary insufficiency, malignant tumors or other major diseases that are not suitable for clinical experiments; 4. Active bleeding in the gastrointestinal tract; 5. Prior treatment with corticosteroids or other immunosuppressants; 6. HBV, HCV, HIV or other untreated infections, congenital or acquired immunodeficiency diseases; 7. Have been vaccinated with live vaccine in the past four weeks; 8. Serum bilirubin \> 3.6mg/dl for at least 1 month or liver function ≥3 times the upper limit of normal value; 9. Allergic to prednisolone, tacrolimus, or ripertamab; 10. Reluctance to use contraception or plan pregnancy/lactation within 6 months of study completion; 11. Had history of alcohol/drug abuse; 12. Unable to give informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse rate at 24 months | Up to 24 months after enrollment | Relapse: Proteinuria\>3.5g/d or PCR\>3500mg/g after complete remission has been achieved. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse rate at 12/18 months | Up to 18 months after enrollment | The relapse rates of MCD patients at 12 months and 18 months were observed |
| The time from clinical complete remission to replase | Up to 24 months after enrollment | — |
| Safety-adverse events | The time from randomization until the occurrence of such adverse events, up to 24 months | Creatinine levels doubled from baseline; an increase ≥30% from eGFR baseline; ESRD; adverse events; drug-related adverse events, and abnormal clinical manifestations |
| Partial or complete remission at 2/6/12/24 months | Up to 24 months after enrollment | Partial remission: Reduction of proteinuria to 0.3-3.5g/d, or PCR 300-3500mg/g and a decrease \>50% from baseline Complete remission: Reduction of proteinuria to \<0.3g/d or PCR\<300mg/g |
| The time from the start of treatment to achieve complete remission | Up to 24 months after enrollment | The time it takes for patients with MCD to reach a state of complete remission needs to be observed |
Contacts
Primary Contactshiren Sun[Author], Doctor
Outcome results
None listed