NephropathyPhase 4NCT05839314
Effect of Huaier Granule on the Treatment of Idiopathic Membranous Nephropathy
A Phase 4 study testing Huaier granule, Renin-angiotensin-aldosterone system inhibitors (RASI) and Ciclosporin soft capsules in people with Nephropathy and Glomerular Diseases, run by Chinese PLA General Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Nephropathy, Glomerular Diseases, Idiopathic Membranous Nephropathy
- What is being tested?
- Huaier granule, Renin-angiotensin-aldosterone system inhibitors (RASI) and Ciclosporin soft capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 480 participants
- Where
- 1 siteChina
- Study dates
- 9 May 2023to 1 Jul 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Chinese PLA general hospital
Beijing, Beijing Municipality
Xiangmei Chen
About this study
Official title: Effect of Huaier Granule on the Treatment of Idiopathic Membranous Nephropathy: a Multicenter, Randomized, Open-label, Parallel Controlled Study
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.
Read the 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.
- Being tested
- Huaier granule, Renin-angiotensin-aldosterone system inhibitors (RASI), Ciclosporin soft capsules
- Keywords
- Huaier granule, Ciclosporin, Idiopathic membranous nephropathy
- Medical subject headings
- Kidney Diseases, Glomerulonephritis, Membranous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Huaier granuleDrug
Also called Jinke
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)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 capsulesDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Huaier group | Experimental | Patients will take Huaier granule and renin-angiotensin-aldosterone system inhibitors (RASI). Receives: Drug: Huaier granule; Drug: Renin-angiotensin-aldosterone system inhibitors (RASI) |
| Ciclosporin soft capsules group | Active comparator | Patients will take Ciclosporin soft capsules and RASI. Receives: Drug: Renin-angiotensin-aldosterone system inhibitors (RASI); Drug: Ciclosporin soft capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Start of randomization until 96 weeks
Secondary outcomes (21)
Rate of complete remission at 24, 48, 96 weeks
The rate of patients achieve complete remission at 24, 48, or 96 weeks.
Measured: Start of randomization until 96 weeks
Rate of partial remission at 24, 48, 96 weeks
The rate of patients achieve partial remission at 24, 48, or 96 weeks.
Measured: Start of randomization until 96 weeks
Median time to achieve complete remission
Measured: Start of randomization until 96 weeks
Median time to achieve partial remission
Measured: Start of randomization until 96 weeks
Median time of the first relapse of nephrotic syndrome for patients who achieve complete remission or partial remission
Measured: Start of randomization until 96 weeks
Proportion of patients with relapse of nephrotic syndrome
Measured: Start of randomization until 96 weeks
Rate of treatment failure at the end of the study
Treatment failure: the efficacy has not reached complete or partial remission
Measured: Start of randomization until 96 weeks
The proportion of reappearance proteinuria (but not reach nephrotic syndrome) for patients with complete response
Measured: Start of randomization until 96 weeks
The 24-hour urinary protein level and changes from baseline at 24, 48, 96 weeks
Measured: Start of randomization until 96 weeks
The serum albumin level and changes from baseline at 24, 48, 96 weeks
Measured: Start of randomization until 96 weeks
Changes of serum creatinine at 24, 48, 96 weeks
Measured: Start of randomization until 96 weeks
Changes of blood urea nitrogen at 24, 48, 96 weeks
Measured: Start of randomization until 96 weeks
Changes of serum uric acid at 24, 48, 96 weeks
Measured: Start of randomization until 96 weeks
Changes of serum blood lipid level at 24, 48, 96 week
Measured: Start of randomization until 96 weeks
The level and changes of estimated glomerular filtration rate (eGFR) calculating using the CKD-EPI formula at 24, 48, 96 weeks
Measured: Start of randomization until 96 weeks
Percentage of patients who serum creatinine doubled for 12 weeks, progress to end-stage renal disease, or receive renal replacement therapy
Measured: Start of randomization until 96 weeks
The number and proportion of patients who died for any reason
Measured: Start of randomization until 96 weeks
The level of phospholipase A2 receptor (PLA2R) and changes from baseline at 24, 48, 96 weeks
Measured: Start of randomization until 96 weeks
The level and changes of immunoglobulin and complement
Measured: Start of randomization until 96 weeks
Incidence and severity of adverse events (AE) and serious adverse events (SAE)
Measured: Start of randomization until 96 weeks
Incidence and severity of adverse reactions (ADR), serious adverse reactions (SADR)
Measured: Start of randomization until 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2023
- Study start9 May 2023
- Primary completion3 May 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NephropathyStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 480 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- LinkDoc Technology (Beijing) Co. Ltd., Huazhong University of Science and Technology
- Responsible party
- Principal investigator, Xiangmei Chen, Chinese PLA General Hospital
- Investigators
- Xiangmei Chen, PhD, Principal investigator, Chinese PLA General Hospital, Beijing, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05839314
- Sponsor's protocol ID
- HE-202009
- Status last verified
- Jun 2024
- First submitted
- 20 Apr 2023
- Last updated
- 4 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Huaier Granule on the Treatment of Idiopathic Membranous Nephropathy: a Multicenter, Randomized, Open-label, Parallel Controlled Study
- ClinicalTrials.gov ID
- NCT05839314
- Acronym / sponsor ID
- HE-202009
- Keywords
- Huaier granule, Ciclosporin, Idiopathic membranous nephropathy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 480 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Collaborators
- LinkDoc Technology (Beijing) Co. Ltd., Huazhong University of Science and Technology
- Study start
- 9 May 2023 (actual)
- Primary completion
- 3 May 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 3 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Huaier group | Experimental | Drug: Huaier granule, Drug: Renin-angiotensin-aldosterone system inhibitors (RASI)Patients will take Huaier granule and renin-angiotensin-aldosterone system inhibitors (RASI). |
| Ciclosporin soft capsules group | Active comparator | Drug: Renin-angiotensin-aldosterone system inhibitors (RASI), Drug: Ciclosporin soft capsulesPatients will take Ciclosporin soft capsules and RASI. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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);
Key exclusion criteria (17 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Huaier granuleAlso: JinkeHuaier 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. | Drug | Huaier group |
| 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. | Drug | Ciclosporin soft capsules group, Huaier group |
| Ciclosporin soft capsulesThe 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. | Drug | Ciclosporin soft capsules group |
Primary outcome
Overall clinical remission rate at 24, 48, 96 weeks
Time frame: Start of randomization until 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.
21 secondary outcomes
Rate of complete remission at 24, 48, 96 weeks
Time frame: Start of randomization until 96 weeks
Rate of partial remission at 24, 48, 96 weeks
Time frame: Start of randomization until 96 weeks
Median time to achieve complete remission
Time frame: Start of randomization until 96 weeks
Median time to achieve partial remission
Time frame: Start of randomization until 96 weeks
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
Proportion of patients with relapse of nephrotic syndrome
Time frame: Start of randomization until 96 weeks
Rate of treatment failure at the end of the study
Time frame: Start of randomization until 96 weeks
The proportion of reappearance proteinuria (but not reach nephrotic syndrome) for patients with complete response
Time frame: Start of randomization until 96 weeks
The 24-hour urinary protein level and changes from baseline at 24, 48, 96 weeks
Time frame: Start of randomization until 96 weeks
The serum albumin level and changes from baseline at 24, 48, 96 weeks
Time frame: Start of randomization until 96 weeks
Changes of serum creatinine at 24, 48, 96 weeks
Time frame: Start of randomization until 96 weeks
Changes of blood urea nitrogen at 24, 48, 96 weeks
Time frame: Start of randomization until 96 weeks
Changes of serum uric acid at 24, 48, 96 weeks
Time frame: Start of randomization until 96 weeks
Changes of serum blood lipid level at 24, 48, 96 week
Time frame: Start of randomization until 96 weeks
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
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
The number and proportion of patients who died for any reason
Time frame: Start of randomization until 96 weeks
The level of phospholipase A2 receptor (PLA2R) and changes from baseline at 24, 48, 96 weeks
Time frame: Start of randomization until 96 weeks
The level and changes of immunoglobulin and complement
Time frame: Start of randomization until 96 weeks
Incidence and severity of adverse events (AE) and serious adverse events (SAE)
Time frame: Start of randomization until 96 weeks
Incidence and severity of adverse reactions (ADR), serious adverse reactions (SADR)
Time frame: Start of randomization until 96 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Xiangmei Chen, PhD principal investigator
Chinese PLA General Hospital, Beijing, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Huaier granule, Renin-angiotensin-aldosterone system inhibitors (RASI) and Ciclosporin soft capsules in people with Nephropathy and Glomerular Diseases, run by Chinese PLA General Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xiangmei Chen, PhD (00-86-010-66937166, shengdai26@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall clinical remission rate at 24, 48, 96 weeks (time frame: Start of randomization until 96 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2024.