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

NCT03418779 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: TCMWINE
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• First occurrence of 40% decrease in eGFR from baseline

  Baseline, until the first occurrence or 3 years

• First occurrence of progression to continuous renal replacement

  Until occurrence or 3 years

• Death due to renal disease

  Until occurrence or 3 years

Secondary Outcomes (3)

• Mean annual reduction in eGFR based on SCr

  48 weeks

• Proteinuria remission

  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

  Week 48

Study Arms (2)

Control Group

EXPERIMENTAL

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

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.

Drug: The Yi-Qi-Qing-Jie herbal compound; Drug: Immunosuppressants; Other: Optimized Supportive Care

Interventions

The Yi-Qi-Qing-Jie herbal compound DRUG

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.

YQF Group

Immunosuppressants DRUG

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.

Also known as: prednisolone, cyclophosphamide

Control Group; YQF Group

Optimized Supportive Care OTHER

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

Control Group; YQF Group

Yi-Qi-Qing-Jie herbal compound placebo OTHER

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.

Control Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guang'anmen Hospital of China Academy of Chinese Medical Sciences: lead
• China Academy of Chinese Medical Sciences: collaborator

Study Sites (1)

Guang anmen Hospital, China Academy of Chinese Medical Sciences

Beijing, Beijing Municipality, 100053, China

Location

Related Publications (2)

• 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.

  PMID: 38299639 DERIVED

• 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.

  PMID: 31907076 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, IGA

Interventions

Immunosuppressive Agents; Prednisolone; Cyclophosphamide

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Jie Wang

  Guang anmen Hospital, China Academy of Chinese Medical Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor & MD.

Study Record Dates

• First Submitted: January 11, 2018
• First Posted: February 1, 2018
• Study Start: July 4, 2019
• Primary Completion: September 25, 2024
• Study Completion: December 31, 2024
• Last Updated: September 25, 2024

Record last verified: 2024-09

Locations

CN (1)