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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)

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

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.

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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 The blinding will be removed only if a participant has severe side effects that the affected participant will be withdrawn.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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

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:

  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

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:

  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




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).



Information from the National Library of Medicine

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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03418779


Contacts
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Contact: Shen Li 010-88001057 lishen58173@163.com
Contact: Jinpu Li 010-88001057 tankey2113@gmail.com

Locations
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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
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Study Chair: Jie Wang Guang anmen Hospital, China Academy of Chinese Medical Sciences
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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    Key Record Dates
Last Update Posted: August 10, 2020
Last Verified: August 2020

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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:
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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