Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A Nephropathy: A Randomized Controlled Trial
Jie Wu1, Shu-Wei Duan1, Xue-Feng Sun1, Wen-Ge Li2, Ya-Ping Wang3, Wen-Hu Liu4, Jian-Rong Zhang5, Li-De Lun6, Xue-Mei Li7, Chun-Hua Zhou8, Ji-Jun Li9, Shu-Wen Liu1, Yuan-Sheng Xie1, Guang-Yan Cai1, Lu Ma10, Wen Huang11, Hua Wu12, Qiang Jia13, Xiang-Mei Chen1
1 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
2 Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China
3 Department of Nephrology, PLA Army General Hospital, Beijing 100700, China
4 Department of Nephrology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
5 Department of Nephrology, General Hospital of Chinese People's Armed Police Forces, Beijing 100039, China
6 Department of Nephrology, Air Force General Hospital of People's Liberation Army, Beijing 100142, China
7 Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
8 Department of Nephrology, Navy General Hospital, Beijing 100048, China
9 Department of Nephrology, First Affiliated Hospital of General Hospital of People's Liberation Army, Beijing 100048, China
10 Treatment Center for Kidney Disease, No. 281 Hospital of Beijing Military Region, Qinhuangdao, Hebei 066100, China
11 Department of Nephrology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
12 Department of Nephrology, Beijing Hospital, Beijing 100730, China
13 Department of Nephrology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
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, 28 Fuxing Road, Beijing 100853
Source of Support: None, Conflict of Interest: None
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.
Trial Registration: chictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.