IgA Nephropathy at High Risk of Developing ESRDPhase 2/3TCMWINENCT03418779
Treatment Effects of Chinese Medicine (Yi-Qi-Qing-Jie Herbal Compound) Combined With Immunosuppression Therapies in IgA Nephropathy Patients With High-risk of ESRD
A Phase 2/3 study testing The Yi-Qi-Qing-Jie herbal compound, Immunosuppressants and Optimized Supportive Care in people with IgA Nephropathy at High Risk of Developing ESRD, run by Guang'anmen Hospital of China Academy of Chinese Medical Sciences at 1 site in China.
Trial summary
The TCM-WINE study is a single-center, prospective, double-blind randomized placebo-controlled trial. Based on optimal supportive care, the trial is aiming to assess superiority with regard to renal protection and reduction of severe treatment-related adverse events of Yi-Qi-Qing-Jie formula (YQF) combined therapy… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- IgA Nephropathy at High Risk of Developing ESRD
- What is being tested?
- The Yi-Qi-Qing-Jie herbal compound, Immunosuppressants and Optimized Supportive Care
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 4 Jul 2019to 31 Dec 2024
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients who maintain regular follow-ups at Guang'anmen Hospital, agree to participate, and provide informed consent;
- biopsy-proven IgA nephropathy, with recent progression to high-risk IgAN*;
- eGFR 15 to 60 ml/min/1.73 m2, calculated with the use of CKD-EPI Creatinine Equation 2009.
- High-risk IgAN: persistent proteinuria ≥ 1 g/d despite at least 8 weeks of optimal supportive care [maximally tolerated RAS blocker which refers to no symptomatic hypotension, no hyperkalemia, and serum creatinine increased by not more than 30% of baseline, blood pressure control meeting targets (135/85 mmHg or lower), and dietary management (sodium intake less than 6 g/d, protein intake of 0.6-0.8 g/kg/day, and low-fat diet)], the mean annual eGFR decline rate (eGFR-slope) >10 ml/min per 1.73 m2 per year, while needing to restart immunosuppressive therapy; or eGFR<60 ml/min/1.73 m2 at the first diagnosis.
Who cannot join
- secondary IgAN;
- comorbidity of other primary or secondary glomerular diseases;
- comorbidity of severe primary diseases such as cardiovascular, hepatic, cerebral, and hematopoietic system diseases or mental disorders;
- allergy or intolerance to the experimental medication (e.g., RAS blockers, prednisolone, cyclophosphamide, YQF compound and its placebo compound);
- contraindications to immunosuppression therapy-acute and chronic infectious diseases, malignancies, leukopenia, thrombocytopenia, gastrointestinal hemorrhage, ulcers of stomach or duodenum, post-transplantation;
- pregnant or lactating women;
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- unwilling to participate in this study, failure to accept or tolerate Chinese medicine compound;
- history of alcohol or drug abuse;
- poor compliance, loss to follow-up;
- participation in another clinical investigation.
Trial locations and contacts
1 site in 1 country.
China1 site
Guang anmen Hospital, China Academy of Chinese Medical Sciences
Beijing, Beijing Municipality, 100053
About this study
Official title: Treatment Effects of Chinese Medicine (Yi-Qi-Qing-Jie Herbal Compound) Combined With Immunosuppression Therapies in IgA Nephropathy Patients With High-risk of End-stage Renal Disease (TCM-WINE)
The TCM-WINE study is a single-center, prospective, double-blind randomized placebo-controlled trial. Based on optimal supportive care, the trial is aiming to assess superiority with regard to renal protection and reduction of severe treatment-related adverse events of Yi-Qi-Qing-Jie formula (YQF) combined therapy compared with immunosuppression monotherapy in high-risk IgAN.
Read the detailed description
The investigators plan to randomize 60 participants with biopsy-proven IgAN to a YQF combined group (YQF compound combined with prednisolone, and cyclophosphamide if necessary) or an immunosuppression group (placebo-YQF combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter a 48-week in-trial treatment phase and receive post-trial follow-up until 50% (30/60) have a composite endpoint or have been followed for 3 years (study completion). All patients will receive optimal supportive care.
- Being tested
- The Yi-Qi-Qing-Jie herbal compound, Immunosuppressants, Optimized Supportive Care, Yi-Qi-Qing-Jie herbal compound placebo
- Keywords
- IgA nephropathy, immunosuppressive therapy, Yi-Qi-Qing-Jie herbal compound, high-risk IgAN, traditional chinese medicine
- Medical subject headings
- Glomerulonephritis, IGA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The Yi-Qi-Qing-Jie herbal compoundDrug
The compounds are blends of individual herbal extracts from YQF (consisting of Astragalus membranaceus, Saposhnikovia divaricata (turcz.) Schischk, Flos lonicerae, Angelica sinensis, Dioscorea nipponica, Hedyotis diffusa Willd, rhubarb, Spatholobus suberectus, with the effect of reinforcing Qi and activating blood, clearing away heat and poison, dissolving dampness and downbearing turbid) dissolved in 150 ml boiled water and taken orally twice a day for the duration of the treatment and follow-up phases.
ImmunosuppressantsDrug
Also called prednisolone, cyclophosphamide
Immunosuppression therapy comprises oral prednisolone (0.5-0.8 mg/kg/day; exact dose decided by the investigator, maximum dose not exceeding 60 mg/day) for 8 weeks, then tapered by 5-10 mg/day every 4 weeks, with a total treatment period of 24-32 weeks. Participants with persistent proteinuria ≥ 1 g/day after 8 weeks of corticosteroid monotherapy will receive 0.8-1.0 g of intravenous cyclophosphamide (CTX) every 4 weeks, total dose of not exceeding 8 g (exact dose decided by the site investigator). If severe CTX-related adverse events occur, such as alanine transaminase (ALT) exceeding the upper limit of two times, infections requiring hospitalization, granulocytes < 3.0 × 109/L and platelets < 50.0 × 109/L, CTX will stop being administered, symptoms will be treated, and adverse events recorded. Also, the frequency of detection will be increased to once every 2 weeks and the affected participant will be withdrawn if persistent infection or myelosuppression occurs.
Optimized Supportive CareOther
The optimized supportive care included:
- Lifestyle: low-salt, restricted protein dietary with sufficient calorie supply, smoking cessation, moderate alcohol consumption and keeping a healthy weight
- The use of renin-angiotensin system blockade: lowering blood pressure to a target below 135/85 mmHg, during which treatment was adjusted to ensure that patients were receiving the maximum labelled or tolerated dose of RAS blockade
- Patients with Diabetes Mellitus received insulin or oral hypoglycemic agents to achieve HbA1c≤ 7.0%
- Received uricosuric agents or xanthine oxidase inhibitors as necessary to achieve serum uric acid <6 mg/dL in female, <7 mg/dL in male
Yi-Qi-Qing-Jie herbal compound placeboOther
Patients will receive Yi-Qi-Qing-Jie herbal compound placebo instead for the duration of the treatment and follow-up phases. The major component of the placebo is malt dextrin which looks, smells and tastes like YQF compound, and it comes in packaging with a similar appearance to YQF compound; it is also dissolved in 150 ml boiled water and taken orally twice a day.
| Study group | Role | What they receive |
|---|---|---|
| Control Group | Experimental | Optimized supportive care, YQF placebo (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide. Receives: Drug: Immunosuppressants; Other: Optimized Supportive Care; Other: Yi-Qi-Qing-Jie herbal compound placebo |
| YQF Group | Experimental | Optimized supportive care, YQF (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide. Receives: Drug: The Yi-Qi-Qing-Jie herbal compound; Drug: Immunosuppressants; Other: Optimized Supportive Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
First occurrence of 40% decrease in eGFR from baseline
Measured: Baseline, until the first occurrence or 3 years
First occurrence of progression to continuous renal replacement
Measured: Until occurrence or 3 years
Death due to renal disease
Measured: Until occurrence or 3 years
Secondary outcomes (3)
Mean annual reduction in eGFR based on SCr
eGFR slope
Measured: 48 weeks
Proteinuria remission
Prescribed as proteinuria < 0.5 g/day
Measured: Week 24, 36, and 48 in the treatment period, and month 6, 12, 24, or 36 if possible
The remission rate of symptoms and inflammation status
The subjective symptoms and inflammation status will be scored on a four-point scale ranging from 0 (absent) to 3 (severe).
Measured: Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2018
- Study start4 Jul 2019
- Primary completion25 Sep 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for IgA Nephropathy at High Risk of Developing ESRDStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- China Academy of Chinese Medical Sciences
- Responsible party
- Principal investigator, Li Shen, Guang'anmen Hospital of China Academy of Chinese Medical Sciences
- Investigators
- Jie Wang, Study chair, Guang anmen Hospital, China Academy of Chinese Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03418779
- Sponsor's protocol ID
- TCMWINE
- Acronym
- TCMWINE
- Status last verified
- Sep 2024
- First submitted
- 11 Jan 2018
- Last updated
- 25 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Tunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.pub3.
PubMed 38299639Li S, Li JP. Treatment effects of Chinese medicine (Yi-Qi-Qing-Jie herbal compound) combined with immunosuppression therapies in IgA nephropathy patients with high-risk of end-stage renal disease (TCM-WINE): study protocol for a randomized controlled trial. Trials. 2020 Jan 6;21(1):31. doi: 10.1186/s13063-019-3989-9.
PubMed 31907076
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Effects of Chinese Medicine (Yi-Qi-Qing-Jie Herbal Compound) Combined With Immunosuppression Therapies in IgA Nephropathy Patients With High-risk of End-stage Renal Disease (TCM-WINE)
- ClinicalTrials.gov ID
- NCT03418779
- Acronym / sponsor ID
- TCMWINE / TCMWINE
- Keywords
- IgA nephropathy, immunosuppressive therapy, Yi-Qi-Qing-Jie herbal compound, high-risk IgAN, traditional chinese medicine
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Guang'anmen Hospital of China Academy of Chinese Medical SciencesUniversity, hospital or other
- Collaborators
- China Academy of Chinese Medical Sciences
- Study start
- 4 Jul 2019 (actual)
- Primary completion
- 25 Sep 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 1 Feb 2018 (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.
The TCM-WINE study is a single-center, prospective, double-blind randomized placebo-controlled trial. Based on optimal supportive care, the trial is aiming to assess superiority with regard to renal protection and reduction of severe treatment-related adverse events of Yi-Qi-Qing-Jie formula (YQF) combined therapy compared with immunosuppression monotherapy in high-risk IgAN.
Detailed description
The investigators plan to randomize 60 participants with biopsy-proven IgAN to a YQF combined group (YQF compound combined with prednisolone, and cyclophosphamide if necessary) or an immunosuppression group (placebo-YQF combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter a 48-week in-trial treatment phase and receive post-trial follow-up until 50% (30/60) have a composite endpoint or have been followed for 3 years (study completion). All patients will receive optimal supportive care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | Experimental | Drug: Immunosuppressants, Other: Optimized Supportive Care, Other: Yi-Qi-Qing-Jie herbal compound placeboOptimized supportive care, YQF placebo (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide. |
| YQF Group | Experimental | Drug: The Yi-Qi-Qing-Jie herbal compound, Drug: Immunosuppressants, Other: Optimized Supportive CareOptimized supportive care, YQF (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- patients who maintain regular follow-ups at Guang'anmen Hospital, agree to participate, and provide informed consent;
- biopsy-proven IgA nephropathy, with recent progression to high-risk IgAN*;
- eGFR 15 to 60 ml/min/1.73 m2, calculated with the use of CKD-EPI Creatinine Equation 2009.
Key exclusion criteria (10 listed)
- secondary IgAN;
- comorbidity of other primary or secondary glomerular diseases;
- comorbidity of severe primary diseases such as cardiovascular, hepatic, cerebral, and hematopoietic system diseases or mental disorders;
- allergy or intolerance to the experimental medication (e.g., RAS blockers, prednisolone, cyclophosphamide, YQF compound and its placebo compound);
- contraindications to immunosuppression therapy-acute and chronic infectious diseases, malignancies, leukopenia, thrombocytopenia, gastrointestinal hemorrhage, ulcers of stomach or duodenum, post-transplantation;
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 |
|---|---|---|
| The Yi-Qi-Qing-Jie herbal compoundThe compounds are blends of individual herbal extracts from YQF (consisting of Astragalus membranaceus, Saposhnikovia divaricata (turcz.) Schischk, Flos lonicerae, Angelica sinensis, Dioscorea nipponica, Hedyotis diffusa Willd, rhubarb, Spatholobus suberectus, with the effect of reinforcing Qi and activating blood, clearing away heat and poison, dissolving dampness and downbearing turbid) dissolved in 150 ml boiled water and taken orally twice a day for the duration of the treatment and follow-up phases. | Drug | YQF Group |
| ImmunosuppressantsAlso: prednisolone, cyclophosphamideImmunosuppression therapy comprises oral prednisolone (0.5-0.8 mg/kg/day; exact dose decided by the investigator, maximum dose not exceeding 60 mg/day) for 8 weeks, then tapered by 5-10 mg/day every 4 weeks, with a total treatment period of 24-32 weeks. Participants with persistent proteinuria ≥ 1 g/day after 8 weeks of corticosteroid monotherapy will receive 0.8-1.0 g of intravenous cyclophosphamide (CTX) every 4 weeks, total dose of not exceeding 8 g (exact dose decided by the site investigator). If severe CTX-related adverse events occur, such as alanine transaminase (ALT) exceeding the upper limit of two times, infections requiring hospitalization, granulocytes < 3.0 × 109/L and platelets < 50.0 × 109/L, CTX will stop being administered, symptoms will be treated, and adverse events recorded. Also, the frequency of detection will be increased to once every 2 weeks and the affected participant will be withdrawn if persistent infection or myelosuppression occurs. | Drug | Control Group, YQF Group |
| Optimized Supportive CareThe optimized supportive care included: 1. Lifestyle: low-salt, restricted protein dietary with sufficient calorie supply, smoking cessation, moderate alcohol consumption and keeping a healthy weight 2. The use of renin-angiotensin system blockade: lowering blood pressure to a target below 135/85 mmHg, during which treatment was adjusted to ensure that patients were receiving the maximum labelled or tolerated dose of RAS blockade 3. Patients with Diabetes Mellitus received insulin or oral hypoglycemic agents to achieve HbA1c≤ 7.0% 4. Received uricosuric agents or xanthine oxidase inhibitors as necessary to achieve serum uric acid <6 mg/dL in female, <7 mg/dL in male | Other | Control Group, YQF Group |
| Yi-Qi-Qing-Jie herbal compound placeboPatients will receive Yi-Qi-Qing-Jie herbal compound placebo instead for the duration of the treatment and follow-up phases. The major component of the placebo is malt dextrin which looks, smells and tastes like YQF compound, and it comes in packaging with a similar appearance to YQF compound; it is also dissolved in 150 ml boiled water and taken orally twice a day. | Other | Control Group |
Primary outcome
First occurrence of 40% decrease in eGFR from baseline
Time frame: Baseline, until the first occurrence or 3 years
First occurrence of progression to continuous renal replacement
Time frame: Until occurrence or 3 years
Death due to renal disease
Time frame: Until occurrence or 3 years
3 secondary outcomes
Mean annual reduction in eGFR based on SCr
Time frame: 48 weeks
Proteinuria remission
Time frame: Week 24, 36, and 48 in the treatment period, and month 6, 12, 24, or 36 if possible
The remission rate of symptoms and inflammation status
Time frame: Week 48
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2024.
- Derived from this study: PubMed 38299639Tunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.pub3.
- Derived from this study: PubMed 31907076Li S, Li JP. Treatment effects of Chinese medicine (Yi-Qi-Qing-Jie herbal compound) combined with immunosuppression therapies in IgA nephropathy patients with high-risk of end-stage renal disease (TCM-WINE): study protocol for a randomized controlled trial. Trials. 2020 Jan 6;21(1):31. doi: 10.1186/s13063-019-3989-9.
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. This study is not recruiting at the moment.
Jie Wang study chair
Guang anmen Hospital, China Academy of Chinese Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing The Yi-Qi-Qing-Jie herbal compound, Immunosuppressants and Optimized Supportive Care in people with IgA Nephropathy at High Risk of Developing ESRD, run by Guang'anmen Hospital of China Academy of Chinese Medical Sciences 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 4 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 25 Sep 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
First occurrence of 40% decrease in eGFR from baseline (time frame: Baseline, until the first occurrence or 3 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03418779, which also lists 2 linked publications.
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 25 Sep 2024.