抗菌药物治疗急性细菌性感染的非劣效试验设计及其定量分析

目的：以氟喹诺酮类药物盐酸安妥沙星片剂临床研究为实例,对抗菌药物治疗急性细菌性感染进行非劣效试验设计,并对研究结果进行定量分析。方法：以左氧氟沙星片剂为对照,采用随机、双盲双模拟、多中心、平行对照、非劣效临床研究。安妥沙星组、左氧氟沙星组各360例。两药均为口服用药,安妥沙星组每日服用盐酸安妥沙星片200mg,首剂加倍;左氧氟沙星组每次200mg,q12h;疗程7～14d。按双模拟方法编盲,以临床有效率为主要疗效指标,非劣效标准（δ）设为0.15（15%）。结果：安妥沙星临床有效率为95.1%,细菌清除率96.4%,不良反应发生率为8.1%;左氧氟沙星临床有效率96.6%,细菌清除率97.6%,不良反应发生率为8.1%。临床有效率组间差异-0.015,95%CI为-0.045,0.015],试验组非劣效于对照组（P〈0.05）。结论：安妥沙星片治疗常见急性细菌性呼吸道、泌尿道和皮肤软组织感染疗效确切,疗效不劣于对照药左氧氟沙星,患者耐受性好,未发现严重不良反应。

Design of a clinical trial of non-inferiority for treating acute bacterial infections and its quantitive analysis

AIM: To design a clinical trial of non-inferiority for treating acute bacterial infections by an example and quantitively analyze the results. METHODS: A randomized, double-blind, multicenter, parallel controlled, and non-inferiority study was designed to compare the efficacy and safety of antofloxacin hydrochloride (200 mg,qd) and levofloxacin (200 mg,q12 h) (n=360). The oral administration lasted 7-14 days. The main end point was clinical efficacy rates. The margin of non-inferiority was 0.15 (15%). RESULTS:After 7-14 days of treatment, no significant difference was found between the two groups either in the efficacy rate (antofloxacin hydrochloride: 95.1%, Levofloxacin: 96.6%, treatment difference, -0.015; 95% confidence interval CI] for the difference, -0.045 to 0.015) or the incidence of adverse reactions (antofloxacin hydrochloride: 8.1%, levofloxacin: 8.1%). CONCLUSION:Antofloxacin hydrochloride is non-inferior to levofloxacin, and well tolerated in the treatment of acute bacterial infections.