研究疾病:
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IgA肾病
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研究疾病代码:
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Target disease:
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IgA nephropathy
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Target disease code:
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研究类型:
Study type:
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干预性研究
Interventional study
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研究设计:
Study design:
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随机平行对照
randomized controlled trial(parallel group design)
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研究所处阶段:
Study phase:
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探索性研究/预试验
Pilot clinical trial
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研究目的:
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通过多中心临床试验评估抗炎症药物羟氯喹或新型雷公藤制剂(昆仙胶囊)与安慰剂相比降低IgA肾病患者蛋白尿的有效性及安全性,探索安全有效的新型治疗策略。
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Objectives of Study:
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A multicenter,clinical,trial was conducted to evaluate the efficacy and safety of an anti-inflammatory agent, hydroxychloroquine, or a new Tripterygium compound (Kunxian capsule) compared with placebo in reducing proteinuria in patients with IgA nephropathy , and to explore a safe and effective new therapeutic strategy.
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药物成份或治疗方案详述:
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符合入组标准的患者将1:1:1随机分为羟氯喹组、昆仙胶囊组及安慰剂组。治疗疗程为12个月,分为6个月诱导治疗阶段及6个月维持治疗阶段。
1.羟氯喹组:接受羟氯喹和昆仙胶囊安慰剂
eGFR>45mL/min/1.73m^2:羟氯喹200mg bid服用6个月,之后改为100mg bid维持治疗6个月;
eGFR30-45mL/min/1.73m^2:羟氯喹100mg bid服用6个月,之后仍然维持100mg bid治疗6个月;
昆仙胶囊安慰剂用法同昆仙胶囊组。
2.昆仙胶囊组:接受昆仙胶囊和羟氯喹安慰剂
eGFR>45mL/min/1.73m^2:昆仙胶囊600mg tid服用6个月,之后改为300mg bid维持治疗6个月;
eGFR30-45mL/min/1.73m^2:昆仙胶囊600mg bid 服用6个月,之后改为300mg bid维持治疗6个月;
羟氯喹安慰剂用法同羟氯喹组。
3.安慰剂组:接受昆仙胶囊安慰剂和羟氯喹安慰剂治疗,具体用法同上。
所有患者均接受IgA肾病标准的支持治疗,包括使用RAS阻断剂治疗和血压控制在指南规定的理想范围内(130/80mmHg)。
昆仙胶囊主要成分为昆明山海棠。
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Description for medicine or protocol of treatment in detail:
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Patients meeting the inclusion criteria were randomly divided into hydroxychloroquine group, Kunxian capsule group and placebo group according to 1:1:1.The treatment course was 12 months, including 6 months of induction therapy and 6 months of maintenance therapy.
1.Hydroxychloroquine group: received Hydroxychloroquine and Quincine capsule placebo.
eGFR > 45mL/min/1.73m^2: Hydroxychloroquine was given 200mg bid for 6 months, followed by 100mg bid for maintenance for 6 months.
eGFR 30-45 mL/min/1.73m^2: Hydroxychloroquine was given 100mg bid for 6 months, followed by 100mg bid for maintenance for 6 months.
Kunxian capsule placebo was used the same as Kunxian capsule group.
2.Kunxian capsule group: received Kunxian capsule and hydroxychloroquine placebo.
eGFR > 45mL/min/1.73m^2: Kunshen capsules 600mg tid for 6 months, followed by 300mg bid maintenance therapy for 6 months.
eGFR 30-45 mL/min/1.73m^2: Kunxian capsule 600mg bid for 6 months, followed by 300mg bid maintenance therapy for 6 months.
Hydroxychloroquine placebo was used the same as the hydroxychloroquine group.
3.Placebo group: receive Kunxian capsule placebo and hydroxychloroquine placebo, the specific usage is the same as above.
All patients received standard IgA nephropathy supportive care.This includes treatment with RAS blockers and blood pressure control within the ideal guidelines (130/80mmHg).
The main ingredient of Kunxian Capsule is Kunming Mountain Begonia.
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纳入标准:
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1.年龄>18岁;
2.肾活检证实的原发性IgA肾病;
3.按照治疗指南推荐的接受最大耐受剂量的RAS阻断剂治疗3月后,尿蛋白仍然大于0.75g/d;
4.eGFR >=30 mL/min/1.73m^2。
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Inclusion criteria
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1.Aged >18 years;
2.Primary IgA nephropathy confirmed by renal biopsy;
3.After 3 months of treatment with the maximum tolerated dose of RAS blocker recommended by treatment guidelines, urinary protein was still greater than 0.75g/d;
4.eGFR >= 30 mL/min/1.73m^2.
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排除标准:
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1.有激素及免疫抑制剂治疗指征的IgA肾病患者, 例如:
(1)伴IgA沉积的微小病变肾病;
(2)过去12个月内,肾活检中大于50%的肾小球中有细胞/细胞纤维新月体;
2.存在其他免疫抑制治疗的指征,如合并间质性肾炎、膜性肾病等;
3.过去6个月内系统使用过激素或其他免疫抑制治疗,或6个月内系统使用过羟氯喹或者雷公藤制剂治疗;
4.恶性高血压或其他不能控制的严重高血压(收缩压>160mmHg或舒张压>110mmHg);
5.过去5年内有恶性肿瘤病史,不包括治疗过的非黑色素瘤皮肤癌(即鳞状或基底细胞癌);
6.肾功能不稳定的其他原因,如大量血尿引起的急性肾损伤(过去的事件不是排除原因);
7.明显的肝病,例如:ALT水平高于正常上限(ULN)的2.0倍,或总胆红素高于ULN的1.5倍;
8.妊娠期或哺乳期女性患者,或存在生育要求的男、女患者;
9.活动的系统感染或在入组前1个月内的严重感染,包括艾滋病病毒、丙型肝炎病毒、乙型肝炎病毒;
10.白细胞计数< 3.0x10^9/L,或贫血(血红蛋白水平低于80g/L),血小板计数低于80x10^9/L,或有其他血液疾病;
11.有活动性消化道溃疡病的证据;
12.合并眼底病变;
13.G6PD酶缺乏或对4氨基喹啉化合物过敏患者,或存在其他使用羟氯喹禁忌患者;
14.研究者认为不能依从研究方案的患者。
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Exclusion criteria:
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1.IgA nephropathy patients with indications of hormonal and immunosuppressive therapy, such as:
(1) Minimal pathological nephropathy with IgA deposition;
(2) In the past 12 months, more than 50% of glomeruli on renal biopsy had cell/cellular fibrous crescents;
2.Other indications of immunosuppressive therapy, such as interstitial nephritis, membranous nephropathy, etc.;
3.Systematic use of hormones or other immunosuppressive therapy within the past 6 months, or systematic use of hydroxychloroquine or Tripterygium wilfordii preparation within the past 6 months;
4.Malignant hypertension or other uncontrolled severe hypertension (systolic blood pressure > 160mmHg or diastolic blood pressure > 110mmHg);
5.A history of malignancy within the past 5 years, excluding treated non-melanoma skin cancer (i.e. squamous or basal cell carcinoma);
6.Other causes of renal instability, such as acute kidney injury due to heavy hematuria (past events are not excluded as causes);
7.Significant liver disease, such as ALT levels 2.0 times higher than the upper normal limit (ULN), or total bilirubin 1.5 times higher than the ULN;
8.Patients who were in lactation or prenancy or had fertility requirements;
9.Active systemic infection or severe infection within 1 month prior to enrolment, including HIV, hepatitis C virus, hepatitis B virus;
10.White blood cell count < 3.0x10^9/L, or anemia (hemoglobin level below 80g/L), platelet count below 80x10^9/L, or other blood disorders;
11.Patients who have evidence of active digestive tract ulcer;
12.Patients who complicated with fundus lesions;
13.Patients with G6PD deficiency or hypersensitivity to 4-aminoquinoline compounds, or with other contraindications to the use of hydroxychloroquine;
14.Patients who the investigator considered unable to comply with the study protocol.
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研究实施时间:
Study execute time:
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从From
2021-01-01
至To
2023-01-01
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征募观察对象时间:
Recruiting time:
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从From
2021-04-10
至To
2022-01-01
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