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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)

Primary Purpose

IgA Nephropathy at High Risk of Developing ESRD

Status

Active

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

The Yi-Qi-Qing-Jie herbal compound

Immunosuppressants

Optimized Supportive Care

Yi-Qi-Qing-Jie herbal compound placebo

About this trial

This is an interventional treatment trial for IgA Nephropathy at High Risk of Developing ESRD focused on measuring IgA nephropathy, immunosuppressive therapy, Yi-Qi-Qing-Jie herbal compound, high-risk IgAN, traditional chinese medicine

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

patients who maintain regular follow-up at Guang'anmen Hospital, agree to participate, and provide informed consent;
in accordance with IgAN pathological diagnosis, 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.

Exclusion Criteria:

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;
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.

Sites / Locations

Guang anmen Hospital, China Academy of Chinese Medical Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Control Group

YQF Group

Arm Description

Optimized supportive care, YQF placebo (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide.

Optimized supportive care, YQF (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide.

Outcomes

Primary Outcome Measures

First occurrence of 40% decrease in eGFR from baseline

First occurrence of progression to continuous renal replacement

Death due to renal disease

Secondary Outcome Measures

Mean annual reduction in eGFR based on SCr

eGFR slope

Proteinuria remission

Prescribed as proteinuria < 0.5 g/day

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).

Full Information

NCT ID

NCT03418779

First Posted

January 11, 2018

Last Updated

September 28, 2023

Sponsor

Guang'anmen Hospital of China Academy of Chinese Medical Sciences

Collaborators

China Academy of Chinese Medical Sciences

1. Study Identification

Unique Protocol Identification Number

NCT03418779

Brief Title

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

Acronym

TCMWINE

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)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

July 4, 2019 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Guang'anmen Hospital of China Academy of Chinese Medical Sciences

Collaborators

China Academy of Chinese Medical Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

IgA Nephropathy at High Risk of Developing ESRD

Keywords

IgA nephropathy, immunosuppressive therapy, Yi-Qi-Qing-Jie herbal compound, high-risk IgAN, traditional chinese medicine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

Participants, investigators, and all other members with clinical involvement in the trial will be blinded to the treatment assignment for the duration of the trial. Relevant personnel have clear divisions of labor and strict permission restrictions. The blinding will be removed only if a participant has severe side effects that the affected participant will be withdrawn.

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Control Group

Arm Type

Experimental

Arm Description

Optimized supportive care, YQF placebo (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide.

Arm Title

YQF Group

Arm Type

Experimental

Arm Description

Optimized supportive care, YQF (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide.

Intervention Type

Drug

Intervention Name(s)

The Yi-Qi-Qing-Jie herbal compound

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Immunosuppressants

Other Intervention Name(s)

prednisolone, cyclophosphamide

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Optimized Supportive Care

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Yi-Qi-Qing-Jie herbal compound placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

First occurrence of 40% decrease in eGFR from baseline

Time Frame

Baseline, until the first occurrence or 3 years

Title

First occurrence of progression to continuous renal replacement

Time Frame

Until occurrence or 3 years

Title

Death due to renal disease

Time Frame

Until occurrence or 3 years

Secondary Outcome Measure Information:

Title

Mean annual reduction in eGFR based on SCr

Description

eGFR slope

Time Frame

48 weeks

Title

Proteinuria remission

Description

Prescribed as proteinuria < 0.5 g/day

Time Frame

Week 24, 36, and 48 in the treatment period, and month 6, 12, 24, or 36 if possible

Title

The remission rate of symptoms and inflammation status

Description

The subjective symptoms and inflammation status will be scored on a four-point scale ranging from 0 (absent) to 3 (severe).

Time Frame

Week 48

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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; 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jie Wang

Organizational Affiliation

Guang anmen Hospital, China Academy of Chinese Medical Sciences

Official's Role

Study Chair

Facility Information:

Facility Name

Guang anmen Hospital, China Academy of Chinese Medical Sciences

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100053

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

31907076

Citation

Li 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.

Results Reference

derived

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

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