硬膜外腔阻滞麻醉药临床等效性试验设计方法及其定量分析  

A design of clinical equivalence trial of local anesthetics for epidural block and its quantitive analysis

作　　者：何迎春[1] 杨娟[1] 吕映华[1] 许羚[1] 黄继汉[1] 盛玉成[1] 陈君超[1] 李禄金[1] 刘红霞[1] 郑青山[1] 

机构地区：[1]上海中医药大学药物临床研究中心计算药物学实验室,上海201203

出　　处：《中国新药与临床杂志》2009年第1期34-38,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：上海市教委重点学科建设项目(J5030a3);上海市科研计划项目(06DZ19728)

摘　　要：目的以甲哌卡因临床研究为实例,研究临床等效试验设计方法,并对研究结果进行定量分析。方法以利多卡因注射液为对照,采用随机、双盲、多中心、平行对照、等效临床研究。甲哌卡因组、利多卡因组各120例。2药均为硬膜外腔注射用药,在注射15mL研究用药物后20min内,感觉阻滞平面上界达到T8判断为有效。以感觉阻滞有效率为主要疗效指标,等效界值δ=±0.10(10%)。结果甲哌卡因感觉阻滞有效率为99.2%;利多卡因感觉阻滞有效率99.1%,感觉阻滞有效率组间差为0.001(0.1%),其双向单侧97.5%CI(-0.022～0.024),提示试验组与对照组具有临床等效性。甲哌卡因不良反应发生率为4.2%,利多卡因不良反应发生率为5.0%。结论临床等效性试验重点在于主要疗效指标选取、等效界值确定和样本量估算,但安全性评价同样不能忽视。AIM To design a clinical equivalence trial for local anesthetics in the use of epidural anesthesia by an example mepivacaine and quantitively analyze the results. METHODS A randomized, doubleblind, multicenter, parallel controlled and clinical equivalence trial was designed to compare the efficacy and safety of mepivacaine and lidocaine （n = 120 for each）. Both local anesthetics were administrated into epidural space, and sensory blockade efficacy rates was defined the upper level of anesthesia to T8 in 20 min after the treatment. The main utes end point was sensory blockade efficacy rates. The margins of equivalence were ＋ 0.10 （10%）. RESULTS Twenty minutes after the treatment, no significant difference was found between the two groups in the sensory blockade efficacy rates （mepivacaine ： 99.2% ; lidocaine.. 99.1% ; treatment difference： 0.001; 97.5% confidence interval [CI] for the difference： -0.022 to 0.024）. The incidence of adverse reactions was 4.2% in mepivacaine, and 5.0% in levofloxacin. Mepivacaine is equivalent to lidocaine. CONCLUSION Defining the primary endpoint, choice of equivalence margin and sample size estimation are critical decision as well as safety evaluation in designing a clinical equivalence trial.

关 键 词：甲哌卡因 利多卡因 麻醉 硬膜外 临床试验 治疗等效 

分 类 号：R971.2[医药卫生—药品]