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

Phase 2

Active, not recruiting

• Conditions: IgA Nephropathy at High Risk of Developing ESRD
• Interventions: Drug: Immunosuppressants; Drug: The Yi-Qi-Qing-Jie herbal compound; Other: Optimized Supportive Care; Other: Yi-Qi-Qing-Jie herbal compound placebo

• Registration Number: NCT03418779
• Lead Sponsor: Guang'anmen Hospital of China Academy of Chinese Medical Sciences

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.

Study Timeline

• Study First Submitted: 2018-01-11
• Study First Submitted QC: 2018-01-25
• Study First Posted: 2018-02-01
• Study Start: 2019-07-04
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-28
• Last Update Posted: 2023-09-29
• Primary Completion: 2023-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Group	Optimized Supportive Care	Optimized supportive care, YQF placebo (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide.
Control Group	Yi-Qi-Qing-Jie herbal compound placebo	Optimized supportive care, YQF placebo (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide.
YQF Group	Optimized Supportive Care	Optimized supportive care, YQF (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide.
Control Group	Immunosuppressants	Optimized supportive care, YQF placebo (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide.
YQF Group	Immunosuppressants	Optimized supportive care, YQF (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide.
YQF Group	The Yi-Qi-Qing-Jie herbal compound	Optimized supportive care, YQF (oral granule), immunosuppression therapy comprises oral prednisolone plus intravenous cyclophosphamide.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Proteinuria remission	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
Mean annual reduction in eGFR based on SCr	48 weeks	eGFR slope
The remission rate of symptoms and inflammation status	Week 48	The subjective symptoms and inflammation status will be scored on a four-point scale ranging from 0 (absent) to 3 (severe).

Trial Locations

Locations (1)

Guang anmen Hospital, China Academy of Chinese Medical Sciences; 🇨🇳 Beijing, Beijing, China