Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

anemia;conversion ratio;darbepoetin alfa;epoetin alfa;hemodialysis

Liu Bicheng;Chen Nan;Zhao Jinghong;Yin Aiping;Wu Xiongfei;Xing Changying;Jiang Gengru;Fu Junzhou;Wang Mei;Wang Rong;Niu Jianying;Fu Ping;Ni Zhaohui;Hou Fanfan;Zhao Jiuyang;Chen Jing;Chen Yuqing;Shi Wei;Chen Jianghua;Li Wenge;Xu Gang;Zhong Ling;Liu Wenhu;Ding Guohua;Kondo Yuichiro;Yue Changhe;Mei Changlin

Department of Nephrology, Zhongda Hospital Southeast University, Nanjing, Jiangsu 210009, China;Department of Nephrology, Ruijin Hospital Shanghai Jiaotong University School of Medicine, Shanghai 200025, China;Department of Nephrology, Xinqiao Hospital of Army Medical University, Chongqing 400037, China;Department of Nephrology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China;Department of Nephrology, Southwest Hospital of Army Medical University, Chongqing 400039, China;Department of Nephrology, Jiangsu Provincial Hospital, Nanjing, Jiangsu 210036, China;Department of Nephrology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China;Department of Nephrology, Guangzhou First People's Hospital, Guangzhou, Guangdong 510180, China;Department of Nephrology, Peking University People's Hospital, Beijing 100044, China;Department of Nephrology, Shandong Provincial Hospital, Jinan, Shandong 250021, China;Department of Nephrology, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China;Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;Department of Nephrology, Renji Hospital Shanghai Jiaotong University School of Medicine, Shanghai 200001, China;Department of Nephrology, Nanfang Hospital Southern Medical University, Guangzhou, Guangdong 510510, China;Department of Nephrology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116023, China;Department of Nephrology, Huashan Hospital, Fudan University, Shanghai 200040, China;Department of Nephrology, Peking University First Hospital, Beijing 100034, China;Department of Nephrology, Guangdong Provincial People's Hospital, Guangzhou, Guangdong 510080, China;Department of Nephrology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China;Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China;Department of Nephrology, Tongji Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, Hubei 430030, China;Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China;Department of Nephrology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China;Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China;R&D Planning Department, R&D Division, Kyowa Kirin Co., Ltd., Tokyo 520-5292, Japan;D&R Office, Kyowa Kirin China Pharmaceutical Co., Ltd., Shanghai 201203, China;Department of Nephrology, Shanghai Changzheng Hospital, Shanghai 200003, China

慢性疾病与转化医学（英文）

[1]Liu Bicheng;Chen Nan;Zhao Jinghong;Yin Aiping;Wu Xiongfei;Xing Changying;Jiang Gengru;Fu Junzhou;Wang Mei;Wang Rong;Niu Jianying;Fu Ping;Ni Zhaohui;Hou Fanfan;Zhao Jiuyang;Chen Jing;Chen Yuqing;Shi Wei;Chen Jianghua;Li Wenge;Xu Gang;Zhong Ling;Liu Wenhu;Ding Guohua;Kondo Yuichiro;Yue Changhe;Mei Changlin-.Efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection for the treatment of renal anemia in Chinese hemodialysis patients: A randomized, open-label, parallel-group, noninferiority phase III trial)[J].慢性疾病与转化医学（英文）,2022(02):134-144

darbepoetin,epoetin,noninferiority,SAS

Efficacy,safety,alfa,injection,replacing,renal,anemia,Chinese,hemodialysis,patients,randomized,open,label,parallel,phase,III,trial,Background,This,study,was,explore,clinical,efficacy,recombinant,human,erythropoietin,rHuEPO,associated,chronic,kidney,failure,undergoing,Method,multicenter,intergroup,control,from,April,September,sites,In,this,members,underwent,intravenous,administration,every,two,weeks,drug,three,times,All,subjects,during,baseline,period,After,that,were,randomly,assigned,changes,average,Hb,concentrations,evaluation,threshold,dl,tested,between,treatments,dependent,hemoglobin,maintenance,target,proportion,also,evaluated,Iron,metabolism,including,serum,iron,total,binding,capacity,ferritin,transferrin,saturation,comparisons,dose,adjustments,groups,analyzed,further,Adverse,events,AEs,observed,compared,conversion,switching,discussed,software,used,perform,statistical,analyses,Descriptive,statistics,demographic,variable,primary,indicators,Results,Four,hundred,sixty,enrolled,ultimately,cases,There,protocol,set,respectively,difference,confidence,interval,lower,limit,Weeks,rates,ranging,within,During,incidence,while,adverse,reactions,those,commonly,Conclusion,overall,consistent

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