title: Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A Nephropathy: A Randomized Controlled Trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.
  
  
  BACKGROUND
  chictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.
authors: 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.
authors: Jie
authors: J
authors: Wu
authors: 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.
authors: Shu-Wei
authors: SW
authors: Duan
authors: 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.
authors: Xue-Feng
authors: XF
authors: Sun
authors: Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China.
authors: Wen-Ge
authors: WG
authors: Li
authors: Department of Nephrology, PLA Army General Hospital, Beijing 100700, China.
authors: Ya-Ping
authors: YP
authors: Wang
authors: Department of Nephrology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors: Wen-Hu
authors: WH
authors: Liu
authors: Department of Nephrology, General Hospital of Chinese People's Armed Police Forces, Beijing 100039, China.
authors: Jian-Rong
authors: JR
authors: Zhang
authors: Department of Nephrology, Air Force General Hospital of People's Liberation Army, Beijing 100142, China.
authors: Li-De
authors: LD
authors: Lun
authors: Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors: Xue-Mei
authors: XM
authors: Li
authors: Department of Nephrology, Navy General Hospital, Beijing 100048, China.
authors: Chun-Hua
authors: CH
authors: Zhou
authors: Department of Nephrology, First Affiliated Hospital of General Hospital of People's Liberation Army, Beijing 100048, China.
authors: Ji-Jun
authors: JJ
authors: Li
authors: 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.
authors: Shu-Wen
authors: SW
authors: Liu
authors: 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.
authors: Yuan-Sheng
authors: YS
authors: Xie
authors: 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.
authors: Guang-Yan
authors: GY
authors: Cai
authors: Treatment Center for Kidney Disease, No. 281 Hospital of Beijing Military Region, Qinhuangdao, Hebei 066100, China.
authors: Lu
authors: L
authors: Ma
authors: Department of Nephrology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
authors: Wen
authors: W
authors: Huang
authors: Department of Nephrology, Beijing Hospital, Beijing 100730, China.
authors: Hua
authors: H
authors: Wu
authors: Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors: Qiang
authors: Q
authors: Jia
authors: 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.
authors: Xiang-Mei
authors: XM
authors: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002681:China; D000077144:Clopidogrel; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007677:Kidney Function Tests; D000077339:Leflunomide; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000077333:Telmisartan; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood; D055815:Young Adult
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D007555:Isoxazoles; D014527:Uric Acid; D000077144:Clopidogrel; D003404:Creatinine; D000077339:Leflunomide; D013988:Ticlopidine; D000077333:Telmisartan