Clinical trial NCT03418779: Treatment Effects of Chinese Medicine (Yi-Qi-Qing-Jie Herbal Compound) Combined With Immunosuppression Therapies in IgA Nephropathy Patients With High-risk of ESRD
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
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
Lead sponsor: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
Sponsor class: OTHER
Collaborators: name: China Academy of Chinese Medical Sciences
First posted: 2018-02-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: First occurrence of 40% decrease in eGFR from baseline
timeFrame: Baseline, until the first occurrence or 3 years
measure: First occurrence of progression to continuous renal replacement
timeFrame: Until occurrence or 3 years
measure: Death due to renal disease
timeFrame: Until occurrence or 3 years
Secondary outcomes:
measure: Mean annual reduction in eGFR based on SCr
timeFrame: 48 weeks
measure: Proteinuria remission
timeFrame: Week 24, 36, and 48 in the treatment period, and month 6, 12, 24, or 36 if possible
measure: The remission rate of symptoms and inflammation status
timeFrame: Week 48
Other outcomes:
Locations:
city: Beijing
country: China
facility: Guang anmen Hospital, China Academy of Chinese Medical Sciences
state: Beijing
Study officials:
affiliation: Guang anmen Hospital, China Academy of Chinese Medical Sciences
name: Jie Wang
role: STUDY_CHAIR
References:
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.