Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy

Shanghai Jiao Tong University

Status: Unknown

Conditions: Tacrolimus; Clinical Trial; Idiopathic Membranous Nephropathy

Treatments: Drug: Tacrolimus; Drug: Prednisone

Study type: Interventional

Funder types: Other

Identifiers

NCT03864250

XH-19-002

Details and patient eligibility

About

This random, open, control and multicenter clinical trial mainly aims to assess the urine protein remission rate of tacrolimus (TAC) monotherapy for idiopathic membranous nephropathy (IMN).

Enrollment: 124 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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 infection, syphilis 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 less than 5 years;
5. Those who received glucocorticoids (prednisone or prednisolone), mycophenolate mofetil, tacrolimus, cyclosporine A, cyclophosphamide, tripterygium and other immunosuppressive agents for treatment within 3 months before screening;
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 exclusion criteria;
4. Those who need to take medications prohibited by the trail;
5. Those with poor compliance or stopping the drug for over 2 weeks;
6. Those with uncontrollable infection;
7. Those whit elevated blood glucose during the treatment, which is still difficult to control after routine treatment by endocrinologists;
8. In the TAC group, the eGFR decreased by >30%, the TAC dose was halved. And the drug concentration and renal function were reviewed after 2 weeks. If the eGFR decreased by <30%, it will continue to be used; if the eGFR still decreased by >30%, the TAC dose continues to halve, or give a minimum dose of 0.5mg / d. And the drug concentration and renal function were reviewed after 2 weeks. If the eGFR decreased by <30%, TAC will continue to be used, otherwise stop the drug;
9. Those whose ALT, AST or bilirubin rises to more than 2 times the upper limit of normal value after treatment, and continues to increase for 2 weeks; those whose ALT, AST or bilirubin rises to more than 2 times the upper limit of normal value after 2 weeks of treatment with liver protection, the drug will be discontinued. If it cannot be recovered after 2 weeks, the patient will withdraw;
10. Those with other unexplained severe comorbidities;
11. Those with pregnancy during treatment;
12. For security reasons, the research sponsor proposed to stop the study;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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124 participants in 2 patient groups

Tacrolimus monotherapy

Experimental group

Treatment:

Drug: Tacrolimus

Tacrolimus combined with hormone therapy

Active Comparator group

Treatment:

Drug: Prednisone

Drug: Tacrolimus