Effect of Huaier Granule on the Treatment of Idiopathic Membranous Nephropathy

NCT ID: NCT05839314

Last Updated: 2024-06-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 480 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-09
• Study Completion Date: 2027-07-01

Brief Summary

This is a prospective, multicenter, randomized, open-label, parallel controlled study. The purpose of this study is to evaluate the efficacy and safety of Huaier granule on the treatment of idiopathic membranous nephropathy comparing with Ciclosporin soft capsules.

Detailed Description

Idiopathic membranous nephropathy (IMN) is a common immune-mediated glomerular disease, accounting for 20% to 36.8% of adult nephrotic syndrome. A third of the patients will experience complete remission spontaneously, and 30%-40% of patients will develop chronic renal failure. The treatment of IMN includes supportive therapy and immunosuppressive therapy. Ciclosporin (CsA) is a kind of calcineurin inhibitor (CNI) recommended by the Kidney disease improving global outcomes (KDIGO) clinical practice guideline for IMN treatment. CsA is effective in inducing remission among patients with steroid-resistant nephrotic IMN, and studies showed the clinical remission rate was 60%-75%. However, it has a high rate of relapse during follow-up in 6-12 months.

Huaier granule is an extract from a medicinal fungus. Previous studies showed that Huaier granule reduced the excretion of proteinuria, inhibited inflammation and cellular transdifferentiation, and protect renal function.

In this study, about 30 research centers will participate. We plan to enroll 480 participants (240 cases in the experimental group and 240 cases in the control group). The planned length of patient recruitment enrolment will be 2 years and the total length of visits be 1 year.

Conditions

Nephropathy; Glomerular Diseases; Idiopathic Membranous Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Huaier group

Patients will take Huaier granule and renin-angiotensin-aldosterone system inhibitors (RASI).

Group Type: EXPERIMENTAL

Huaier granule

Intervention Type: DRUG

Huaier granule, oral administration, 10g each time, 3 times a day, continuous medication for 24 weeks. After 24 weeks of treatment, the dosage should be adjusted according to efficacy.

Renin-angiotensin-aldosterone system inhibitors (RASI)

Intervention Type: DRUG

Run-in period: All the patients should be treated with RASI for at least 4 weeks, and stop using any medicine containing Huaier or similar ingredients for at least 2 weeks before enrollment. If the patient is receiving RASI, the RASI can be continued until the end of the study. RASI can be adjusted once a week until the maximum tolerable dose based on albuminuria and blood pressure. If the patient is not receiving RASI therapy, then RASI is recommended.

Treatment period: RASI therapy is continued throughout the trial. Check blood pressure twice daily: morning and evening.

Ciclosporin soft capsules group

Patients will take Ciclosporin soft capsules and RASI.

Group Type: ACTIVE_COMPARATOR

Renin-angiotensin-aldosterone system inhibitors (RASI)

Intervention Type: DRUG

Run-in period: All the patients should be treated with RASI for at least 4 weeks, and stop using any medicine containing Huaier or similar ingredients for at least 2 weeks before enrollment. If the patient is receiving RASI, the RASI can be continued until the end of the study. RASI can be adjusted once a week until the maximum tolerable dose based on albuminuria and blood pressure. If the patient is not receiving RASI therapy, then RASI is recommended.

Treatment period: RASI therapy is continued throughout the trial. Check blood pressure twice daily: morning and evening.

Ciclosporin soft capsules

Intervention Type: DRUG

The initial dose of Ciclosporin soft capsules is an oral dose of 3.5mg/kg/d, divided into two equal doses, given every 12 hours. Assess the plasma concentration of CsA (valley value) every 2 weeks in the first 8 weeks. If the plasma concentration of CsA reaches 100-150ug/L, continue to maintain the dose. If the plasma concentration of CsA is below the target concentration, increase the dose of CsA. If the plasma concentration of CsA is higher than the upper limit of the target concentration, appropriate dose reduction. A single dose adjustment is 25mg/d. After increasing/decreasing the dose, CsA concentration is remeasured at intervals of 2 weeks ±3 days until the target concentration is reached.

CsA at target concentration followed by 24 weeks of treatment, then the dosage shall be adjusted according to efficacy.

Interventions

Huaier granule

Huaier granule, oral administration, 10g each time, 3 times a day, continuous medication for 24 weeks. After 24 weeks of treatment, the dosage should be adjusted according to efficacy.

Intervention Type: DRUG

Renin-angiotensin-aldosterone system inhibitors (RASI)

Run-in period: All the patients should be treated with RASI for at least 4 weeks, and stop using any medicine containing Huaier or similar ingredients for at least 2 weeks before enrollment. If the patient is receiving RASI, the RASI can be continued until the end of the study. RASI can be adjusted once a week until the maximum tolerable dose based on albuminuria and blood pressure. If the patient is not receiving RASI therapy, then RASI is recommended.

Treatment period: RASI therapy is continued throughout the trial. Check blood pressure twice daily: morning and evening.

Intervention Type: DRUG

Ciclosporin soft capsules

The initial dose of Ciclosporin soft capsules is an oral dose of 3.5mg/kg/d, divided into two equal doses, given every 12 hours. Assess the plasma concentration of CsA (valley value) every 2 weeks in the first 8 weeks. If the plasma concentration of CsA reaches 100-150ug/L, continue to maintain the dose. If the plasma concentration of CsA is below the target concentration, increase the dose of CsA. If the plasma concentration of CsA is higher than the upper limit of the target concentration, appropriate dose reduction. A single dose adjustment is 25mg/d. After increasing/decreasing the dose, CsA concentration is remeasured at intervals of 2 weeks ±3 days until the target concentration is reached.

CsA at target concentration followed by 24 weeks of treatment, then the dosage shall be adjusted according to efficacy.

Intervention Type: DRUG

Other Intervention Names

Jinke

Eligibility Criteria

Inclusion Criteria

• Renal biopsy was performed before randomization and pathologically diagnosed as idiopathic membranous nephropathy;
• Anti-phospholipase a2 receptor (PLA2R) antibody is positive;
• Aged from 18 to 75, either sex;
• Tolerable doses of RASI were received for ≥4 weeks before randomization, nephrotic syndrome was not in remission and 24-hour urinary protein level was ≥3.5g/24h and < 8.0g/24h;
• The eGFR≥45ml/min/1.73m2 (Measured at least twice in 2 weeks);
• The patient is willing to sign the informed consent form.

Exclusion Criteria

• Diagnosed as secondary membranous nephropathy;
• Rapidly progressive membranous nephropathy (eGFR decreased by 50 % compared with the baseline level within 3 months);
• Receiving renal replacement therapy;
• Diabetes and glycosylated hemoglobin (HbA1c) levels ≥ 7.0%;
• Hypertension is not well controlled (systolic blood pressure>160mmHg or diastolic blood pressure>100mmHg);
• The level of serum albumin≤20g/L;
• Resistance to treatment with CsA or other CNI, rituximab (RTX) or alkylating agents; complete remission or partial remission was obtained after treatment with CNI, RTX, or alkylating agents but there was a history of relapse within 3 months；
• Suspected infection by imaging and/or laboratory tests;
• Infectious diseases, such as hepatitis B, hepatitis C, AIDS, tuberculosis;
• History of malignant tumor;
• Hepatic dysfunction: aspartate aminotransferase (AST) concentration and alanine aminotransferase (ALT) concentration of > 1.5 × upper limit of normal;
• Allergic to Huaier granule or Ciclosporin soft capsules;
• Previous CNI treatment was ineffective;
• Complicate with any diseases that may affect efficacy and safety evaluation;
• Pregnant or lactating women, and patients (male or female) with fertility plans or unwilling to take effective contraceptive measures;
• Participating in other clinical trials or participated in other clinical studies within 3 months;
• According to the researchers, patients have diseases or conditions that increase the difficulty of enrollment or probability of loss to follow-up, such as mental illness, frequent changes in residence and work, etc.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

LinkDoc Technology (Beijing) Co. Ltd.

INDUSTRY

Sponsor Role: collaborator

Huazhong University of Science and Technology

OTHER

Sponsor Role: collaborator

Chinese PLA General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiangmei Chen

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiangmei Chen, PhD

Role: PRINCIPAL_INVESTIGATOR

Chinese PLA General Hospital, Beijing, China

Locations

Chinese PLA general hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiangmei Chen, PhD

Role: CONTACT

shengdai26@163.com

00-86-010-66937166

Facility Contacts

Xiangmei Chen

Role: primary

Other Identifiers

HE-202009

Identifier Type: -

Identifier Source: org_study_id