Treatment Effects of Chinese Medicine (Yi-Qi-Qing-Jie Herbal Compound) Combined With Immunosuppression Therapies in IgA Nephropathy Patients With High-risk of ESRD (TCMWINE)

September 28, 2023 updated by: Li Shen, Guang'anmen Hospital of China Academy of Chinese Medical Sciences

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100053
        • Guang anmen Hospital, China Academy of Chinese Medical Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. patients who maintain regular follow-ups at Guang'anmen Hospital, agree to participate, and provide informed consent;
  2. biopsy-proven IgA nephropathy, with recent progression to high-risk IgAN*;

  3. 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.

Exclusion Criteria:

  1. secondary IgAN;
  2. comorbidity of other primary or secondary glomerular diseases;
  3. comorbidity of severe primary diseases such as cardiovascular, hepatic, cerebral, and hematopoietic system diseases or mental disorders;
  4. allergy or intolerance to the experimental medication (e.g., RAS blockers, prednisolone, cyclophosphamide, YQF compound and its placebo compound);
  5. contraindications to immunosuppression therapy-acute and chronic infectious diseases, malignancies, leukopenia, thrombocytopenia, gastrointestinal hemorrhage, ulcers of stomach or duodenum, post-transplantation;
  6. pregnant or lactating women;
  7. unwilling to participate in this study, failure to accept or tolerate Chinese medicine compound;
  8. history of alcohol or drug abuse;
  9. poor compliance, loss to follow-up;
  10. participation in another clinical investigation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Control Group
Optimized supportive care, YQF placebo (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide.
Drug: Immunosuppressants
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.
Other Names:
  • prednisolone
  • cyclophosphamide
Other: Optimized Supportive Care

The 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: Yi-Qi-Qing-Jie herbal compound placebo
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.
Experimental: YQF Group
Optimized supportive care, YQF (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide.
Drug: Immunosuppressants
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.
Other Names:
  • prednisolone
  • cyclophosphamide
Other: Optimized Supportive Care

The 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
Drug: The Yi-Qi-Qing-Jie herbal compound
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
First occurrence of 40% decrease in eGFR from baseline
Time Frame: Baseline, until the first occurrence or 3 years
Baseline, until the first occurrence or 3 years
First occurrence of progression to continuous renal replacement
Time Frame: Until occurrence or 3 years
Until occurrence or 3 years
Death due to renal disease
Time Frame: Until occurrence or 3 years
Until occurrence or 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean annual reduction in eGFR based on SCr
Time Frame: 48 weeks
eGFR slope
48 weeks
Proteinuria remission
Time Frame: Week 24, 36, and 48 in the treatment period, and month 6, 12, 24, or 36 if possible
Prescribed as proteinuria < 0.5 g/day
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
The subjective symptoms and inflammation status will be scored on a four-point scale ranging from 0 (absent) to 3 (severe).
Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guang'anmen Hospital of China Academy of Chinese Medical Sciences

Collaborators

China Academy of Chinese Medical Sciences

Investigators

  • Study Chair: Jie Wang, Guang anmen Hospital, China Academy of Chinese Medical Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 4, 2019

Primary Completion (Estimated)

December 31, 2023

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

January 11, 2018

First Submitted That Met QC Criteria

January 25, 2018

First Posted (Actual)

February 1, 2018

Study Record Updates

Last Update Posted (Actual)

September 29, 2023

Last Update Submitted That Met QC Criteria

September 28, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TCMWINE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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