Idiopathic Membranous Nephropathy
Conditions
Brief summary
The trial is a random, open, control and monocentric trial. Mainly to assess the urine protein remission rate of tacrolimus (TAC) monotherapy for idiopathic membranous nephropathy (IMN). Assuming that the urine protein remission rate of 48-week TAC for monotherapy of IMN is not lower than that in treatment group of TAC combined with glucocorticoid, attempt on de-hormonal therapy in the future IMN therapy can be attempted on the basis of the trial results.
Interventions
DRUGTacrolimus
Tacrolimus capsules: 0.5mg/pill, 50 pills/box, AstellasPharma (China) Co., Ltd.; Tacrolimus capsules: 1mg/pill, 50 pills/box, Hangzhou ZhongmeiHuadong Pharmacy Co., Ltd. Start to administer on the randomized grouping day (D0) with an initial dose by weight: initial dose of 0.05-0.075mg/kg/d (bid) following a strict administration interval of 12 hours or fasting or 2 hours after meal. Adjust TAC dose according to 24-hour urine protein, plasma concentration and eGFR changes. It is recommended that plasma trough concentration should be remained at 5-8ng/ml and TAC dose during the whole therapy stage should not be lower than 0.5mg/d. Drugs should be stopped if the 6-month therapy is ineffective. After 6-month therapy, for those whose urine protein achieved complete remission (CR) or partial remission (PR), TAC dose should be reduced gradually with a total therapy duration of 48 weeks.
DRUGPrednisone
Glucocorticoid (prednisone): 5mg/pill, 100 pills/bottle: Shanghai Sine Pharmaceutical Factory Co., Ltd. The initial dose of prednisone should be 0.5mg/kg/d orally (maximum dose of 40mg/d) and administration should be continued for 8-12 weeks; then reduced by the monthly decreased amount of 0.1mg/kg/d till to 0.2mg/kg/d (5-10mg) to maintain. Prednisone should be stopped after administration for the entire 48 weeks.
Sponsors
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
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; 2. Those whose clinical manifestation and renal biopsy pathologic diagnosis are IMN (Stages I-IV) with secondary membranous nephropathy excluded; 3. Those who meet any of the following high-risk IMN standards: * Urinary protein\>8g/24h * Serum albumin\<25g/l * Serum PLA2R levels are 5 times higher than normal * eGFR decline rate after confirmed IMN within 6-12 months is ≥30% * Patients with serious complications: pulmonary embolism, lower extremity static Vein thrombosis/embolism, acute renal injury, etc. 4. Those without reaching the above high-risk IMN standard, but their course of disease is \>6 months without spontaneous remission,and still present nephrotic syndrome; 5. Patients who have signed the informed consent forms.
Exclusion criteria
1. Those whose kidney pathological manifestation of interstitial fibrosis is \>30%; 2. Those who are positive in active Hepatitis B (including HBsAg, HBeAg and HBcAb or HBsAg, HBeAb and HBC) or serological indexes (HBsAg or/and HBeAg or/and HBcAb) or infected with Hepatitis C, tuberculosis, cytomegalovirus, severe fungal or HIV infection; 3. Those who suffer from untreated active digestive tract ulcer within 3 months before random grouping; 4. Those who suffer from uncured malignant tumor for less than 5 years 5. Those who received glucocorticoid (prednisone or prednisolone), mycophenolatemofetil, tacrolimus, cyclosporine A and other drugs for treatment within 3 months before screen with a course of treatment exceeding 4 weeks or those who received cyclophosphamide (accumulated dose\>1.0g); 6. Those whose ALT, AST or total bilirubin content goes beyond 1.5 times above normal upper limit; 7. Those who suffer from combined critical complications such as serious infection or other severe organ disease or dysfunction; 8. Pregnant or lactating women; 9. Those who are known to be allergic to drugs under trial or relevant products; 10. Those who participated in other clinical trials within 3 months before inclusion; 11. The patients who cannot comply with the research proposal as determined by the supervising physician. Exit criteria 1. Those with incomplete or partial relieved proteinuria for 6 months after treatment; 2. Patients or their legal guardians voluntarily requests to withdraw; 3. Those against the inclusion criteria and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission rate of 24-hour urine protein | At week 48 | The proportion of patients with complete remission of 24-hour urine protein in the total evaluated patients. Evaluation criteria of complete remission: post-therapy urine protein level is \<0.3g/24h. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Partial remission remission rate of 24-hour urine protein | At week 48 | The proportion of patients with partial remission of 24-hour urine protein in the total evaluated patients. Evaluation criteria of partial remission: post-therapy urine protein decline is \>50% compared with the peak value. |
| PLA2R antibody negative conversion rate | At week 48 | The proportion of patients with PLA2R antibody negative conversion in the total evaluated patients. Evaluation criteria of negative conversion: PLA2R antibody level is \<20RU/ml. |
| Number of patients with adverse events | up to 48 weeks | Number of patients with adverse events |
Countries
China
Contacts
Primary ContactFujun Lin, MD,PhD
Outcome results
None listed