胃动力药临床试验方案

胃动力药临床试验 双黄连注射液治疗乌头碱中毒临床试验方案 一、研究题目:双黄连注射液治疗乌头碱中毒所导致的室性心率失常的临床研究 二、试验目的:评价双黄连注射液治疗乌头碱中毒所导致的室性心率失常的疗效及不良反应。 三、病例选择: (一) 入选:1.年龄在20-50岁之间;2.具有急性乌头碱中毒的临床现;3.试验前4周经胃镜检查排除胃肠肿瘤、消化性溃疡;4.超声检查排除肝胆道系统疾病;5.试验前72小时内已停用影响本试验的抗胆碱药物、解痉药;6.病人知情同意接受本试验。 (二) 排除标准:1.妊娠或哺乳期妇女;2.伴有其他严重疾病患者包括肝、肾、心血管疾病;3.合并精神疾病或严重神经官能症患者;4.不能表达主观不适症状者。 (三) 脱落病例处理:1、脱落的定义:所有填写了知情同意书并筛选合格进入随机化试验的受试者，无论何时何因退出，只要没有完成方案所的观察周期的受试者，均为脱落病例，未满一个疗程症状消失自行停药者，不作为脱落病例。2、脱落病例的处理:(1)当受试者脱落后，研究者应采取登门预约电话信件等方式，尽可能与受试者联系询问理由记录最后一次服药时间完成所能完成的评估项目。(2)因过敏反应、不良反应、治疗无效而退出试验病例，研究者应根据受试者实际情况采取相应的治疗措施。(3)研究者应填写中止试验的主要原因记录。(4)凡是入选并已使用编号药物的病人无论是否脱落，均应记录和保留观察病历既做留档也是进行意向性分析(ITT)所需，所有脱落病例均应交组长单位汇总， qualification for steel pressure vessels 7 JB/4709-2000 8 JB4730-2005 pressure vessel welding procedures of steel pressure vessel NDT 9 JB/T4744-2000 steel pressure vessel products mechanical properties test of welded plate II, mechanical equipment installation engineering 1 GB150-98 2 GB50128-2005 vertical cylindrical steel pressure vessel steel welded tank code for construction and acceptance of 3 JB/ T4735-1997 steel welded atmospheric pressure vessel 4 GB50231-2009 mechanical equipment installation engineering construction and acceptance specification for 5 GB50275-98 compressor, fan and pump installation engineering construction and acceptance specification for lifting 6 HG20201-2000 construction installation engineering construction standard 7, HG ... Pressure gauges, using an installed spark arrestor for acetylene cylinders, illegal carrying, using gas cylinders, each operator fined 20 Yuan. Gas bottle without the hot sun exposure measures, responsibilities of team a fine of 50 Yuan. (7) at height and the opening and provisional protective measures have been taken, the responsible unit fined 200 Yuan, construction person in charge a fine of 50 Yuan. (8) no permit to work and the job in accordance with the provisions, on the job unit fined 300 yuan, the unit will charge a fine of 100 Yuan. 7.5.3 accident penalties (1) injuries fatalities directly punished 1~2 million. Direct responsibility for the accident and have the corresponding 统计分析。 (四) 剔除标准:1(不符合纳入标准; (五) 退出标准:1(本人或家属不同意;2(资料不全等影响疗效或安全性判定者;3(发生严重的不良事件，并发症或特殊生理变化，不宜接受继续治疗(发生不良反应者应记入不良反应统计);4(盲法试验中由于严重不良事件或临床特殊治疗需要被破盲的个别病例;5(合用影响疗效的药物。 四、试验方法: (一)实验设计:将100例重度乌头碱中毒所致快速性房颤患者随机分为治疗组及对照组。对照组50例给予催吐、洗胃、导泻、输液及抗心律失常治疗; 治疗组50例不经催吐、洗胃、导泻等排除毒物处理, 给予双黄连注射液静滴。观察两组患者症状缓解时间及症状消失时间, 并监测临床指标的监测, 包括血压、脉搏、呼吸、神智及大小便情况, 胸闷、心悸, 恶心、呕吐、腹泻, 口舌及全身麻木感等症状的改善;实验室检查包括血尿常规;心电图及心电监护; 入院即记录临床情况, 并采血, 留尿送实验室检查, 进行心电监护, 心电图,记录临床症状改善时间、临床症状消失时间及心电图恢复正常的时间。 比较两组结果的差异。 (二)治疗方法:所有患者入院后即予以平卧、吸氧、建立静脉通路。治疗组以双黄连注射液( 哈尔滨制药三厂生产) 300 mL静滴, 林格氏液500mL 或5% GNS 静滴等。对照组采用既往治疗方案 : 促进毒物排出, 给予催吐, 洗胃, 导泻;林格氏液500mL 或5% GNS 静滴; 抗心律失常药物选用心律平、胺碘酮。 (三)疗效评估:? 痊愈:临床症状全部消失心电图恢复正常。?显效:临床症状大部分消失，心电图心率失常有所好转(阵发性心动过速和房颤得以控制)。 qualification for steel pressure vessels 7 JB/4709-2000 8 JB4730-2005 pressure vessel welding procedures of steel pressure vessel NDT 9 JB/T4744-2000 steel pressure vessel products mechanical properties test of welded plate II, mechanical equipment installation engineering 1 GB150-98 2 GB50128-2005 vertical cylindrical steel pressure vessel steel welded tank code for construction and acceptance of 3 JB/ T4735-1997 steel welded atmospheric pressure vessel 4 GB50231-2009 mechanical equipment installation engineering construction and acceptance specification for 5 GB50275-98 compressor, fan and pump installation engineering construction and acceptance specification for lifting 6 HG20201-2000 construction installation engineering construction standard 7, HG ... Pressure gauges, using an installed spark arrestor for acetylene cylinders, illegal carrying, using gas cylinders, each operator fined 20 Yuan. Gas bottle without the hot sun exposure measures, responsibilities of team a fine of 50 Yuan. (7) at height and the opening and provisional protective measures have been taken, the responsible unit fined 200 Yuan, construction person in charge a fine of 50 Yuan. (8) no permit to work and the job in accordance with the provisions, on the job unit fined 300 yuan, the unit will charge a fine of 100 Yuan. 7.5.3 accident penalties (1) injuries fatalities directly punished 1~2 million. Direct responsibility for the accident and have the corresponding ?有效:临床症状全部消失，心电图有所改善，过早出现次数、阵速、房颤等降至前至少50%或持续时间降至以前至少50%。4无效:临床症状无改善或加重。分别于入院12、24、48小时对疗效进行评估。 (四)安全性评价 (五)临床试验记录:1(全部病例均按照以上方案观察认真填写病例报告表。2. 所有受试者均应填写患者日记。3. 认真记录患者的服药情况，如全部服用有时漏服有一半以上未服等情况进行详细记录说明。4. 临床试验中各种试验数据要认真记录各种化验检测报告单粘贴在病例报告表上。5. 病例报告表必须按填写说明要求填写。 (六)不良事件的记录和报告方法:治疗过程中任何新出现的其他症状均以不良事件记录，应将其症状程度出现时间持续时间处理措施经过等记录于观察表并且在综合考虑合并症，合并用药基础上评价其与试验药物的相关性，并由医师详细记录。不良事件的分级标准:轻度:有症状出现，但很轻微;中度:症状稍重，但能很好地耐受，不影响正常工作;重度:症状影响正常生活，病人难以忍受，需要停药或对症处理;严重:症状严重，危机病人生命，致死或致残，须立即停药或紧急处理。严重不良事件的处理:(1)发现不良事件时，观察医师可根据病情决定是否终止观察，对因不良反应而停药的病例应进行追踪调查详细记录结果。(2)发现严重不良事件，研究者应立即对受试者采取应当的保护措施，并在24小时内报告申办者、伦理委员会、省级以上药品监督管理局，研究者要在报告签名并注明日期。(3)发现严重不良事件需要紧急破盲时，应由临床试验组长单位负责人、申办者共同破盲，并详细记录破盲过程。 qualification for steel pressure vessels 7 JB/4709-2000 8 JB4730-2005 pressure vessel welding procedures of steel pressure vessel NDT 9 JB/T4744-2000 steel pressure vessel products mechanical properties test of welded plate II, mechanical equipment installation engineering 1 GB150-98 2 GB50128-2005 vertical cylindrical steel pressure vessel steel welded tank code for construction and acceptance of 3 JB/ T4735-1997 steel welded atmospheric pressure vessel 4 GB50231-2009 mechanical equipment installation engineering construction and acceptance specification for 5 GB50275-98 compressor, fan and pump installation engineering construction and acceptance specification for lifting 6 HG20201-2000 construction installation engineering construction standard 7, HG ... Pressure gauges, using an installed spark arrestor for acetylene cylinders, illegal carrying, using gas cylinders, each operator fined 20 Yuan. Gas bottle without the hot sun exposure measures, responsibilities of team a fine of 50 Yuan. (7) at height and the opening and provisional protective measures have been taken, the responsible unit fined 200 Yuan, construction person in charge a fine of 50 Yuan. (8) no permit to work and the job in accordance with the provisions, on the job unit fined 300 yuan, the unit will charge a fine of 100 Yuan. 7.5.3 accident penalties (1) injuries fatalities directly punished 1~2 million. Direct responsibility for the accident and have the corresponding 五、受试者权益保障及知情同意书: 本试验方案须经伦理委员会审议同意并签署批准意见后，方能实施。伦理委员会的意见可以是同意、作必要的修改后同意、不同意、终止或暂停已批准的试验。 参加临床试验的医师必须向受试者提供有关临床试验的详细情况，包括试验目的、试验性质，可能的受益和危险，可供选用的其他治疗方法以及符合赫尔辛基宣言规定的受试者的权利和义务等，使受试者了解后表示同意，并志愿签署知情同意书后，方可进行临床试验。 六、临床试验的质量控制: 在临床试验开始之前对参加试验的临床医师进行统一培训。参加临床试验的医师应相对固定。受试者应按方案要求及时复诊，对未及时复诊病例，研究者应进行随访。对于病人的依从性，住院病人，每次服药由护士送药到口，门诊病人要做好家属或护理人员的工作，使其理解试验的意义，由家属或护理人员监督病人服药。申办单位应对本试验派出监察员对整个试验进行监察协调，以保证本试验的进度和质量。 七、数据管理及统计方法: (一) 数据管理:1(病例报告表(CRF):每个入选病例都必须完成CRF表，完成的原始CRF表为申办单位所拥有，未经申办单位书面同意，不得以任何形式提供给第三者，除非国家药品监督管理局要求。2(数据库的建立:所有数据将采用计算机独立地进行双份录入，由软件自动核对并根据核对结果进行相应的修改。在此期间，将有疑问表通过临床监查员转交研究者进行数据审核，研究者 qualification for steel pressure vessels 7 JB/4709-2000 8 JB4730-2005 pressure vessel welding procedures of steel pressure vessel NDT 9 JB/T4744-2000 steel pressure vessel products mechanical properties test of welded plate II, mechanical equipment installation engineering 1 GB150-98 2 GB50128-2005 vertical cylindrical steel pressure vessel steel welded tank code for construction and acceptance of 3 JB/ T4735-1997 steel welded atmospheric pressure vessel 4 GB50231-2009 mechanical equipment installation engineering construction and acceptance specification for 5 GB50275-98 compressor, fan and pump installation engineering construction and acceptance specification for lifting 6 HG20201-2000 construction installation engineering construction standard 7, HG ... Pressure gauges, using an installed spark arrestor for acetylene cylinders, illegal carrying, using gas cylinders, each operator fined 20 Yuan. Gas bottle without the hot sun exposure measures, responsibilities of team a fine of 50 Yuan. (7) at height and the opening and provisional protective measures have been taken, the responsible unit fined 200 Yuan, construction person in charge a fine of 50 Yuan. (8) no permit to work and the job in accordance with the provisions, on the job unit fined 300 yuan, the unit will charge a fine of 100 Yuan. 7.5.3 accident penalties (1) injuries fatalities directly punished 1~2 million. Direct responsibility for the accident and have the corresponding 应尽快回答并返回。随机抽取10,的CRF表人工检查一遍，考察是否存在数据出错。完成后由统计人员再对数据进行盲态审核，确认所建立的数据库正确后，由主要研究者、申办者、数据管理人员和统计分析人员对数据进行锁定。锁定后的数据文件不允许再作变动。3(揭盲与数据处理:在数据锁定后，由申办单位、组长单位和统计学专家进行第一次揭盲，将病例分为两组，按统计计划书要求进行统计分析，在完成统计分析后，再进行第二次揭盲，确定试验组和对照组，所有过程均记录见证人。4(资料保存:为保证国家药品监督管理局和申办单位的评价与监督，研究者应同意保存所有研究资料，包括对所有参加受试者的确认(能有效地核对不同的记录资料，如CRF表和医院原始记录)、所有原始的有签名的患者知情同意书、所有CRF表、药品分发的详细记录等。 (二) 数据处理:1(资料描述:计数资料采用构成比描述，计量资料采用均数?标准差描述，非正态分布资料采用中位数、百分位数(第25,第75百分位数)描述。2(基线数据比较:计数资料两组比较采用pearson卡方检验或Fisher检验;正态分布的计量资料采用成组t检验;非正态分布的计量资料采用非参数符号检验。3(疗效比较:两组症状分级、症状疗效、症状积分的总疗效、胃排空等采用用Wilcoxon rank-sum test检验。两组症状积分和胃内钡条残留率的基线比较、治疗后比较、治疗前后差值的组间比较均采用t检验，组内前后比较采用配对t检验。4(安全性评价:实验室检查中定量数据两组比较采用t检验。同时对全部实验室检查数据按是否正常分类，按试验组和对照组分别描述治疗前后正常和异常例数。不良事件采用发生率描述，并详细描述二组病例出现的全部不良事件的具体表现、程度及其与药物的关系。 qualification for steel pressure vessels 7 JB/4709-2000 8 JB4730-2005 pressure vessel welding procedures of steel pressure vessel NDT 9 JB/T4744-2000 steel pressure vessel products mechanical properties test of welded plate II, mechanical equipment installation engineering 1 GB150-98 2 GB50128-2005 vertical cylindrical steel pressure vessel steel welded tank code for construction and acceptance of 3 JB/ T4735-1997 steel welded atmospheric pressure vessel 4 GB50231-2009 mechanical equipment installation engineering construction and acceptance specification for 5 GB50275-98 compressor, fan and pump installation engineering construction and acceptance specification for lifting 6 HG20201-2000 construction installation engineering construction standard 7, HG ... Pressure gauges, using an installed spark arrestor for acetylene cylinders, illegal carrying, using gas cylinders, each operator fined 20 Yuan. Gas bottle without the hot sun exposure measures, responsibilities of team a fine of 50 Yuan. (7) at height and the opening and provisional protective measures have been taken, the responsible unit fined 200 Yuan, construction person in charge a fine of 50 Yuan. (8) no permit to work and the job in accordance with the provisions, on the job unit fined 300 yuan, the unit will charge a fine of 100 Yuan. 7.5.3 accident penalties (1) injuries fatalities directly punished 1~2 million. Direct responsibility for the accident and have the corresponding 八、资料及保存: 资料总结:要求对该药的临床疗效及安全性，在各项数据按统计学要求进行 统计学处理后作出总的评价。资料保存:研究者要保存所有研究资料，包括对受 试者的确认记录、病例报告表、知情同意书、药物分发记录等。研究者应保存临 床试验资料至临床试验工作终止后5年;申办者应保存临床试验资料至试验药物 被批准上市后5年。 qualification for steel pressure vessels 7 JB/4709-2000 8 JB4730-2005 pressure vessel welding procedures of steel pressure vessel NDT 9 JB/T4744-2000 steel pressure vessel products mechanical properties test of welded plate II, mechanical equipment installation engineering 1 GB150-98 2 GB50128-2005 vertical cylindrical steel pressure vessel steel welded tank code for construction and acceptance of 3 JB/ T4735-1997 steel welded atmospheric pressure vessel 4 GB50231-2009 mechanical equipment installation engineering construction and acceptance specification for 5 GB50275-98 compressor, fan and pump installation engineering construction and acceptance specification for lifting 6 HG20201-2000 construction installation engineering construction standard 7, HG ... Pressure gauges, using an installed spark arrestor for acetylene cylinders, illegal carrying, using gas cylinders, each operator fined 20 Yuan. Gas bottle without the hot sun exposure measures, responsibilities of team a fine of 50 Yuan. (7) at height and the opening and provisional protective measures have been taken, the responsible unit fined 200 Yuan, construction person in charge a fine of 50 Yuan. (8) no permit to work and the job in accordance with the provisions, on the job unit fined 300 yuan, the unit will charge a fine of 100 Yuan. 7.5.3 accident penalties (1) injuries fatalities directly punished 1~2 million. Direct responsibility for the accident and have the corresponding