Tacrolimus Monotherapy for Idiopathic Membranous Nephropathy (IMN)

Not Applicable

• Conditions: Idiopathic Membranous Nephropathy
• Interventions: Drug: Tacrolimus; Drug: Prednisone

• Registration Number: NCT03549663
• Lead Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-05-10
• Study First Submitted QC: 2018-06-07
• Study First Posted: 2018-06-08
• Study Start: 2018-07-04
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-01
• Last Update Posted: 2019-04-03
• Primary Completion: 2020-10
• Study Completion: 2021-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 108

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tacrolimus monotherapy	Tacrolimus	-
Tacrolimus combined with hormone therapy	Prednisone	-
Tacrolimus combined with hormone therapy	Tacrolimus	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Shanghai Xinhua Hospital affliated to Shanghai Jiao Tong University, School of Medicine; 🇨🇳 Shanghai, Shanghai, China