Back to resultsEffect of Huaier Granule on the Treatment of Idiopathic Membranous Nephropathy
Primary Purpose
Nephropathy, Glomerular Diseases, Idiopathic Membranous Nephropathy
Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Huaier granule
Renin-angiotensin-aldosterone system inhibitors (RASI)
Ciclosporin soft capsules
Sponsored by
About this trial
This is an interventional treatment trial for Nephropathy focused on measuring Huaier granule, Ciclosporin, Idiopathic membranous nephropathy
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 ≥12 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; History of 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Huaier group
Ciclosporin soft capsules group
Arm Description
Patients will take Huaier granule and renin-angiotensin-aldosterone system inhibitors (RASI).
Patients will take Ciclosporin soft capsules and RASI.
Outcomes
Primary Outcome Measures
Overall clinical remission rate at 24, 48, 96 weeks
Overall clinical remission rate is defined as rate of complete remission and partial remission. Complete remission is defined as a 24-h urinary protein level < 0.3g/d with normal serum albumin level and stable renal function. Partial remission is defined as 24-h urinary protein level < 3.5g/d with peak value reduction ≥ 50%, accompanied by improved or normal serum albumin, stable renal function.
Secondary Outcome Measures
Rate of complete remission at 24, 48, 96 weeks
The rate of patients achieve complete remission at 24, 48, or 96 weeks.
Rate of partial remission at 24, 48, 96 weeks
The rate of patients achieve partial remission at 24, 48, or 96 weeks.
Median time to achieve complete remission
Median time to achieve partial remission
Median time of the first relapse of nephrotic syndrome for patients who achieve complete remission or partial remission
Proportion of patients with relapse of nephrotic syndrome
Rate of treatment failure at the end of the study
Treatment failure: the efficacy has not reached complete or partial remission
The proportion of reappearance proteinuria (but not reach nephrotic syndrome) for patients with complete response
The 24-hour urinary protein level and changes from baseline at 24, 48, 96 weeks
The serum albumin level and changes from baseline at 24, 48, 96 weeks
Changes of serum creatinine at 24, 48, 96 weeks
Changes of blood urea nitrogen at 24, 48, 96 weeks
Changes of serum uric acid at 24, 48, 96 weeks
Changes of serum blood lipid level at 24, 48, 96 week
The level and changes of estimated glomerular filtration rate (eGFR) calculating using the CKD-EPI formula at 24, 48, 96 weeks
Percentage of patients who serum creatinine doubled for 12 weeks, progress to end-stage renal disease, or receive renal replacement therapy
The number and proportion of patients who died for any reason
The level of phospholipase A2 receptor (PLA2R) and changes from baseline at 24, 48, 96 weeks
The level and changes of immunoglobulin and complement
Incidence and severity of adverse events (AE) and serious adverse events (SAE)
Incidence and severity of adverse reactions (ADR), serious adverse reactions (SADR)
Full Information
NCT ID
NCT05839314
First Posted
April 20, 2023
Last Updated
May 4, 2023
Sponsor
Chinese PLA General Hospital
Collaborators
LinkDoc Technology (Beijing) Co. Ltd., Huazhong University of Science and Technology
1. Study Identification
Unique Protocol Identification Number
NCT05839314
Brief Title
Effect of Huaier Granule on the Treatment of Idiopathic Membranous Nephropathy
Official Title
Effect of Huaier Granule on the Treatment of Idiopathic Membranous Nephropathy: a Multicenter, Randomized, Open-label, Parallel Controlled Study
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 1, 2023 (Anticipated)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
June 30, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese PLA General Hospital
Collaborators
LinkDoc Technology (Beijing) Co. Ltd., Huazhong University of Science and Technology
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nephropathy, Glomerular Diseases, Idiopathic Membranous Nephropathy
Keywords
Huaier granule, Ciclosporin, Idiopathic membranous nephropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
480 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Huaier group
Arm Type
Experimental
Arm Description
Patients will take Huaier granule and renin-angiotensin-aldosterone system inhibitors (RASI).
Arm Title
Ciclosporin soft capsules group
Arm Type
Active Comparator
Arm Description
Patients will take Ciclosporin soft capsules and RASI.
Intervention Type
Drug
Intervention Name(s)
Huaier granule
Other Intervention Name(s)
Jinke
Intervention Description
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
Intervention Name(s)
Renin-angiotensin-aldosterone system inhibitors (RASI)
Intervention Description
Run-in period: All the patients should be treated with RASI for at least 12 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
Intervention Name(s)
Ciclosporin soft capsules
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall clinical remission rate at 24, 48, 96 weeks
Description
Overall clinical remission rate is defined as rate of complete remission and partial remission. Complete remission is defined as a 24-h urinary protein level < 0.3g/d with normal serum albumin level and stable renal function. Partial remission is defined as 24-h urinary protein level < 3.5g/d with peak value reduction ≥ 50%, accompanied by improved or normal serum albumin, stable renal function.
Time Frame
Start of randomization until 96 weeks
Secondary Outcome Measure Information:
Title
Rate of complete remission at 24, 48, 96 weeks
Description
The rate of patients achieve complete remission at 24, 48, or 96 weeks.
Time Frame
Start of randomization until 96 weeks
Title
Rate of partial remission at 24, 48, 96 weeks
Description
The rate of patients achieve partial remission at 24, 48, or 96 weeks.
Time Frame
Start of randomization until 96 weeks
Title
Median time to achieve complete remission
Time Frame
Start of randomization until 96 weeks
Title
Median time to achieve partial remission
Time Frame
Start of randomization until 96 weeks
Title
Median time of the first relapse of nephrotic syndrome for patients who achieve complete remission or partial remission
Time Frame
Start of randomization until 96 weeks
Title
Proportion of patients with relapse of nephrotic syndrome
Time Frame
Start of randomization until 96 weeks
Title
Rate of treatment failure at the end of the study
Description
Treatment failure: the efficacy has not reached complete or partial remission
Time Frame
Start of randomization until 96 weeks
Title
The proportion of reappearance proteinuria (but not reach nephrotic syndrome) for patients with complete response
Time Frame
Start of randomization until 96 weeks
Title
The 24-hour urinary protein level and changes from baseline at 24, 48, 96 weeks
Time Frame
Start of randomization until 96 weeks
Title
The serum albumin level and changes from baseline at 24, 48, 96 weeks
Time Frame
Start of randomization until 96 weeks
Title
Changes of serum creatinine at 24, 48, 96 weeks
Time Frame
Start of randomization until 96 weeks
Title
Changes of blood urea nitrogen at 24, 48, 96 weeks
Time Frame
Start of randomization until 96 weeks
Title
Changes of serum uric acid at 24, 48, 96 weeks
Time Frame
Start of randomization until 96 weeks
Title
Changes of serum blood lipid level at 24, 48, 96 week
Time Frame
Start of randomization until 96 weeks
Title
The level and changes of estimated glomerular filtration rate (eGFR) calculating using the CKD-EPI formula at 24, 48, 96 weeks
Time Frame
Start of randomization until 96 weeks
Title
Percentage of patients who serum creatinine doubled for 12 weeks, progress to end-stage renal disease, or receive renal replacement therapy
Time Frame
Start of randomization until 96 weeks
Title
The number and proportion of patients who died for any reason
Time Frame
Start of randomization until 96 weeks
Title
The level of phospholipase A2 receptor (PLA2R) and changes from baseline at 24, 48, 96 weeks
Time Frame
Start of randomization until 96 weeks
Title
The level and changes of immunoglobulin and complement
Time Frame
Start of randomization until 96 weeks
Title
Incidence and severity of adverse events (AE) and serious adverse events (SAE)
Time Frame
Start of randomization until 96 weeks
Title
Incidence and severity of adverse reactions (ADR), serious adverse reactions (SADR)
Time Frame
Start of randomization until 96 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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 ≥12 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;
History of 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiangmei Chen, PhD
Phone
00-86-010-66937166
Email
shengdai26@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiangmei Chen, PhD
Organizational Affiliation
Chinese PLA General Hospital, Beijing, China
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Effect of Huaier Granule on the Treatment of Idiopathic Membranous Nephropathy
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