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)

• ClinicalTrials.gov Identifier: NCT03418779
• Recruitment Status: Recruiting
• First Posted: February 1, 2018
• Last Update Posted: August 10, 2020
• Sponsor: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
• Collaborator: China Academy of Chinese Medical Sciences
• Information provided by (Responsible Party): Li Shen, Guang'anmen Hospital of China Academy of Chinese Medical Sciences

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.

Condition or disease	Intervention/treatment	Phase
IgA Nephropathy at High Risk of Developing ESRD	Drug: The Yi-Qi-Qing-Jie herbal compound; Drug: Immunosuppressants; Other: Optimized Supportive Care; Other: Yi-Qi-Qing-Jie herbal compound placebo	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes 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 The blinding will be removed only if a participant has severe side effects that the affected participant will be withdrawn.
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: July 4, 2019
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

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: 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; 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: 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.; 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: 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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Mean annual reduction in eGFR based on SCr [ Time Frame: 48 weeks ]
   eGFR slope
2. 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
3. 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

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

Contacts and Locations

Contacts

Contact: Shen Li; 010-88001057; lishen58173@163.com

Contact: Jinpu Li; 010-88001057; tankey2113@gmail.com

Locations

China, Beijing

Guang anmen Hospital, China Academy of Chinese Medical Sciences; Recruiting

Beijing, Beijing, China, 100053

Contact: Shen Li 010-88001057 lishen58173@163.com

Contact: Jinpu Li 010-88001057

Sponsors and Collaborators

Guang'anmen Hospital of China Academy of Chinese Medical Sciences

China Academy of Chinese Medical Sciences

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Li Shen, Professor & MD., Guang'anmen Hospital of China Academy of Chinese Medical Sciences
• ClinicalTrials.gov Identifier: NCT03418779
• Other Study ID Numbers: TCMWINE
• First Posted: February 1, 2018
• Last Update Posted: August 10, 2020
• Last Verified: August 2020

• 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

Keywords provided by Li Shen, Guang'anmen Hospital of China Academy of Chinese Medical Sciences:

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

Additional relevant MeSH terms:

Kidney Diseases; Glomerulonephritis, IGA; Urologic Diseases; Glomerulonephritis; Nephritis; Autoimmune Diseases; Immune System Diseases; Prednisolone; Cyclophosphamide; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal