Clinical trial NCT03549663: Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy (IMN)
Official title: Random, Open, Control and Monocentric Clinical Research on Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy (IMN)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Idiopathic Membranous Nephropathy
Lead sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2018-06-08
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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;

Primary outcomes:
measure: Complete remission rate of 24-hour urine protein
timeFrame: At week 48
Secondary outcomes:
measure: Partial remission remission rate of 24-hour urine protein
timeFrame: At week 48
measure: PLA2R antibody negative conversion rate
timeFrame: At week 48
measure: Number of patients with adverse events
timeFrame: up to 48 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Xinhua Hospital affliated to Shanghai Jiao Tong University, School of Medicine
state: Shanghai
Study officials:
affiliation: Shanghai Xinhua Hospital affiliated to Shanghai Jiao Tong University, School of Medicine
name: Fujun Lin, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
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