Wu Jie, Duan Shu-Wei, Sun Xue-Feng, Li Wen-Ge, Wang Ya-Ping, Liu Wen-Hu, Zhang Jian-Rong, Lun Li-De, Li Xue-Mei, Zhou Chun-Hua, Li Ji-Jun, Liu Shu-Wen, Xie Yuan-Sheng, Cai Guang-Yan, Ma Lu, Huang Wen, Wu Hua, Jia Qiang, Chen Xiang-Mei
Department of Nephrology, Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China.
Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China.
Chin Med J (Engl). 2016 Aug 20;129(16):1894-903. doi: 10.4103/0366-6999.187848.
The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN.
It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry.
The effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18-0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44-96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54-12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (-6.72 [95% CI-9.46 to -3.98] ml·min-1·1.73 m-2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed.
Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.
chictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.
替米沙坦联合氯吡格雷、来氟米特或两种药物治疗免疫球蛋白A肾病（IgAN）的疗效和安全性尚不清楚。本研究旨在评估替米沙坦联合氯吡格雷、来氟米特或两种药物治疗IgAN的疗效和安全性。
这是一项多中心、前瞻性、双盲随机对照试验。2010年7月至2012年6月，在中国北京的13个肾脏单位招募原发性IgAN患者。在进行4周的替米沙坦（80mg/d）导入期后，400例继续服用80mg/d替米沙坦的患者被随机分配，额外接受安慰剂（A组）、50mg/d氯吡格雷（B组）、20mg/d来氟米特（C组）或50mg/d氯吡格雷和20mg/d来氟米特（D组）。360例患者完成了24周的干预。主要终点是24周时24小时蛋白尿的变化。采用线性混合效应模型分析第4、12和24周的变化。使用广义估计方程评估血尿等级的变化。本试验在中国临床试验注册中心注册。
替米沙坦联合来氟米特对蛋白尿变化（0.36[95%置信区间（CI）0.18 - 0.55]g/d，P < 0.001）、血清尿酸变化（76.96[95%CI 57.44 - 96.49]μmol/L，P < 0.001）、血清肌酐变化（9.49[95%CI 6.54 - 12.44]μmol/L，P < 0.001）和估计肾小球滤过率变化（-6.72[95%CI - 9.46至 - 3.98]ml·min-1·1.73m-2，P < 0.001）的影响具有统计学意义，而对收缩压和舒张压及体重变化无统计学意义（P > 0.05）。替米沙坦联合氯吡格雷对任何结局均无统计学作用，且干预之间无相互作用。未观察到明显不良反应。
替米沙坦联合来氟米特而非氯吡格雷对某些IgAN患者降低蛋白尿是安全有效的。
chictr.org.cn，ChiCTR - TRC - 10000776；http://www.chictr.org.cn/showproj.aspx?proj = 8760
Zotero 插件