研究疾病:
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原发中危膜性肾病
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研究疾病代码:
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Target disease:
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primary membranous nephropathy with moderate risk
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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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上市后药物
Post-marketing clinical trial
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研究目的:
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在常规应用肾素-血管紧张素系统阻滞剂及其他降压等支持治疗的背景下,评价火把花根片联合他克莫司,相比他克莫司单药对于中危膜性肾病患者在降低蛋白尿方面的疗效和安全性。
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Objectives of Study:
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The purpose of this study is to evaluate?the efficacy and safety of Colquhounia Root Tablets combined with tacrolimus, compared to tacrolimus, in reducing proteinuria in patients with membranous nephropathy who are at moderate risk of disease progression. All patients continued optimized renin-angiotensin system blockers or other antihypertensive as supportive treatments throughout the trial.
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药物成份或治疗方案详述:
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受试者将被按照 1:1 比例随机分配到为期12个月对照组和试验组:
1.对照组:他克莫司胶囊联合安慰剂
2.试验组:他克莫司胶囊联合火把花根片
所有受试者同时也将接受指南要求的无激素或免疫抑制剂的标准基础治疗
诱导期治疗:第1-6个月
他克莫司:对照组和试验组统一方案
1)他克莫司初始剂量 0.05 mg/kg/d,分2次空腹口服;
2)检测血药谷浓度在5-10 ng/ml,依据血药浓度调整药物剂量。
火把花根片/安慰剂:
1)火把花根片/安慰剂 5粒TID口服用治疗连续6个月。
维持期治疗:第7-12个月
患者蛋白尿较基线减少≥ 50%:
1)他克莫司调整血药谷浓度至3-6 ng/ml,至研究结束;
2)火把花根片/安慰剂减量至4粒TID,口服3个月;减量至3粒TID,至研究结束。
患者蛋白尿减少了不到 50% :治疗失败
1)如患者病情稳定,他克莫司调整血药谷浓度至3-6 ng/ml,火把花根片/安慰剂减量至4粒TID,3个月;减量至3粒TID,至研究结束;
如患者病情加剧(如24h尿蛋白定量>8g),依据患者病情调整治疗方案。
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Description for medicine or protocol of treatment in detail:
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Participants will be randomized 1:1 to a 12-month control group and intervention group
1.Control group: tacrolimus capsules combined with placebo
2.Intervention group: tacrolimus capsules combined with Colquhounia Root Tablets
All subjects will continue standard basic treatment without hormones or immunosuppressive agents as required by the guidelines
Induction treatment: from the 1st to 6th month
Tacrolimus (TAC):
The same treatment regimen will be used in the intervention group and the control group
1.TAC will be initiated on a starting dose of 0.05 mg/kg/day p.o., divided into two equal doses given at 12-h intervals,
2.The dose is adjusted according to the target trough blood concentration of 5–10 ng/ml.
Colquhounia Root Tablet (CRT)/placebo:
1.CRT/placebo will be given 5 tablets TID orally.
Maintenance treatment: from the 7th to 12th month
If The patients proteinuria decreased by ≥ 50% from baseline:
1.The dose of TAC will be adjusted according to the target trough blood concentration of 3–6 ng/ml,
2.The dose of CRT/placebo will be adjusted to 4 tablets TID for 3 months and adjusted to 3 tablets TID for the last 3 months.
If The patients proteinuria decreased by less than 50%: (treatment failed)
1.If the patient’s condition is stable, the dose of TAC will be adjusted according to the target trough blood concentration of 3–6 ng/ml, and the dose of CRT/placebo adjusted to 4 tablets of TID for 3 months, adjust the dose to 3 tablets of TID for the last 3 months.
2.If the patient's condition deteriotated (such as urine protein > 8g/d), the treatment regimen will be adjusted according to the patient's condition.
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纳入标准:
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1.年龄45 - 75岁;
2.5年内肾活检证实和符合MN的临床表现和血清学检查的患者并评估排除其他因素确诊为原发性膜性肾病;
3.依据指南建议最大剂量或最大耐受剂量服用稳定剂量的ACEi和/或ARB和/或他汀类药物和/或利尿剂。ACEi或ARB的剂量至少8周内必须保持稳定,定义为8周内剂量变化< 25%;
4.患者蛋白尿水平,≥3.5g/ 天,<8g/ 天;
5.eGFR ≥ 60 ml/min/1.73平米。
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Inclusion criteria
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1.Age 45-75 years old;
2.Those whose clinical manifestation and renal biopsy pathologic diagnosis are PMN with secondary membranous nephropathy excluded;
3.Those who take a stable dose of ACEi and/or ARB and/or statins and/or diuretics in accordance with the maximum dose or maximum tolerated dose recommended by the guidelines for at least 8 weeks, which is defined as a dose change of <25% within 8 weeks;
4.Urinary protein ≥3.5g/day and <8g/day;
5.Estimated GFR ≥ 60 ml/min/1.73m2;
6.Patients who have signed the informed consent forms.
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排除标准:
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1.继发性膜性肾病(如由乙型肝炎、红斑狼疮、药物、恶性肿瘤等引起);
2.PLA2R抗体 > 150 RU/ml;
3.体重>90KG;
4.患者有生育需求;
5.在过去 3 月内使用过免疫抑制剂或1年内使用CD20单抗治疗;
6.无法解释的6个月内eGFR下降20%(eGFR下降不是膜性肾病以外的原因引起的,如肾素-血管紧张素阻滞剂的起始治疗或血容量减少);
7.患者存在严重的、致残的或者威胁生命的与肾病综合征相关的并发症;
8.患者血清白蛋白水平 < 20g/L;
9.移植肾患者;
10.正在或计划怀孕及哺乳的患者;
11.14 天内有活动性全身细菌、病毒(包括 COVID-19)或真菌感染或疑似感染存在(根据研究者判断),或有重度复发性细菌感染病史;或7 天内出现发热 ≥ 38°;或人类免疫缺陷病毒(HIV)感染病史;或有明确诊断的慢性乙型肝炎(HBV)或丙型肝炎(HCV);
12.明显的肝脏疾病,如ALT大于上限值的2倍,或总胆红素大于上限值的1.5倍;
13.恶性或未控制的高血压(收缩压>160mmHg 或舒张压>110mmHg);
14.血白细胞计数<3.0×109/L,或血红蛋白<80g/L,或血小板<80×109/L,或其他血液系统疾病;
15.有糖尿病病史;
16.心力衰竭(NYHA III-IV级);
17.严重心率失常;
18.发生过脑卒中、TIA、急性心肌梗死、不稳定型心绞痛或心源性或不明原因的晕厥;
19.有恶性肿瘤史;
20.有活动性消化性溃疡病史或消化道出血病史;
21.主管医生认为不能依从研究方案的病人;
22.其他医学情况或相关实验室检测结果,研究者认为不适合参加该研究。
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Exclusion criteria:
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1.Those who are secondary cause of MN (eg. hepatitis B, lupus erythematosus, drugs, malignant tumors, etc.);
2.PLA2R antibody > 150 RU/ml;
3.Those whose weight >90KG;
4.Those who have fertility needs;
5.Those who have used immunosuppression in the past 3 months or used CD20 monoclonal antibody treatment within 1 year;
6.Those whose eGFR decrease with unexplained reasons in by 20% within 6 months (The decrease is not caused by PMN);
7.Those who has serious, disabling or life-threatening complications related to PMN;
8.Serum albumin level <20g/L;
9.Those with kidney transplantation;
10.Those who are or plan to become pregnant or breastfeeding;
11.Those who infected by active systemic bacterial, virus (including COVID-19) or fungal infection or suspected infection within 14 days, or history of severe recurrent bacterial infection; or fever ≥ 38° within 7 days; or history of human immunodeficiency virus (HIV) infection; or chronic hepatitis B (HBV) or hepatitis C (HCV) with a clear diagnosis;
12.Those who have obvious liver disease, such as ALT greater than 2 times the upper limit, or total bilirubin greater than 1.5 times the upper limit;
13.Those whose have malignant or uncontrolled hypertension (systolic blood pressure >160mmHg or diastolic blood pressure >110mmHg);
14.Those whose have white blood cell count <3.0×109/L, or hemoglobin <80g/L, or platelets <80×109/L, or other blood system diseases;
15.Those who have a history of diabetes;
16.Those with heart failure (NYHA III-IV grade);
17.Those with severe arrhythmia;
18.Those with stroke, TIA, acute myocardial infarction, unstable angina, or cardiogenic or unexplained syncope occurred;
19.Those with a history of malignant tumors;
20.Those with a history of active peptic ulcer or gastrointestinal bleeding;
21.Those who cannot comply with the research protocol by research sponsor;
22.For security reasons, the research sponsor proposed to stop the study.
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研究实施时间:
Study execute time:
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从From
2021-12-29
至To
2024-03-29
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征募观察对象时间:
Recruiting time:
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从From
2022-04-29
至To
2023-04-30
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