研究人员对新的四价登革热疫苗在亚洲健康儿童中的临床效果和安全性进行了一项3期随机、观察者盲法、安慰剂对照试验,发现对亚洲流行地区的2-14岁儿童在0612月注射3次登革热疫苗是有效的,并且有良好的安全性。疫苗可以减少有症状的感染发生和入院就诊,具有潜在的重要的公共卫生效益。

20141011日《柳叶刀》

 

中文翻译


 

【题目】新四价登革热疫苗在亚洲健康儿童中的临床效果和安全性:3期随机、观察者盲法、安慰剂对照试验

【译文】

背景:预计每年有10亿人罹患有症状的登革热。本研究是第一次报道一项3期登革热候选疫苗的有效性试验。目的是评价CYD登革热疫苗在儿童中对有症状的病毒学确诊的登革热的有效性。

方法:我们在亚洲-太平洋地区的5个国家,进行了一项观察者单盲、随机对照的多中心3期试验。在201163日到121日之间,通过计算机产生的6个具有交互语音或网络应答系统的排列区块,对2-14岁的健康儿童进行随机分配(2:1),在0612个月,接受重组减毒活四价登革热疫苗(CYD-TDV)注射或安慰剂。随机抽样按照年龄和地区分层。随访时间为25个月。研究人员负责准备和注射疫苗,儿童分组对他们不采用盲法,但是不包括儿童的随访。分组对研究的赞助者、观察者、家长和监护人均采用盲法。我们的主要目的是评估在第三次注射的28天之后,疫苗对有症状的病毒学确诊的登革热的有效性,并不区分该病的严重程度和血清型。主要观察终点是疫苗有效性超过25%95%可信区间的下限。研究采用意向性治疗分析和完成治疗分析方法。本试验在ClinicalTrials.gov注册,编号为:NCT01373281。

结果:我们随机分配10275个儿童接受疫苗(6851)或安慰剂(3424)注射,主要分析中分别包含了两组中的6710(98%)3350(98%)。第三次注射28天后发生了250例血清学确诊的登革热(疫苗组117[47%],对照组133[53%])。主要观察终点到达56.5%(95%CI 43.8-66.4)有效率。我们记录了647例严重的副反应事件(疫苗组402[62%],对照组245[38%])。疫苗组有54[1%],对照组33[1%]在疫苗注射后28天内发生严重副反应事件。严重副反应事件与该年龄组的医学异常、主要感染和损伤一致。

结论:我们的研究显示,对亚洲流行地区的2-14岁儿童在0612月注射3次登革热疫苗是有效的,并且有良好的安全性。疫苗可以减少有症状的感染发生和入院就诊,具有潜在的重要的公共卫生效益。

 

英文原稿


 

[Title] Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase
3, randomised, observer-masked, placebo-controlled trial

[Authors] Capeding MR, Tran NH, Hadinegoro SR, Ismail HI, Chotpitayasunondh T, Chua MN, et al.

[Abstract]

BACKGROUND: An estimated 100 million people have symptomatic dengue infection every year. This
is the first report of a phase 3 vaccine efficacy trial of a candidate dengue vaccine. We aimed to assess
the efficacy of the CYD dengue vaccine against symptomatic, virologically confirmed dengue in children.

METHODS: We did an observer-masked, randomised controlled, multicentre, phase 3 trial in five
countries in the Asia-Pacific region. Between June 3, and Dec 1, 2011, healthy children aged 2-14
years were randomly assigned (2:1), by computer-generated permuted blocks of six with an interactive
voice or web response system, to receive three injections of a recombinant, live, attenuated, tetravalent
dengue vaccine (CYD-TDV), or placebo, at months 0, 6, and 12. Randomisation was stratified by age
and site. Participants were followed up until month 25. Trial staff responsible for the preparation and
administration of injections were unmasked to group allocation, but were not included in the follow-up
of the participants; allocation was concealed from the study sponsor, investigators, and parents and
guardians. Our primary objective was to assess protective efficacy against symptomatic, virologically
confirmed dengue, irrespective of disease severity or serotype, that took place more than 28 days
after the third injection. The primary endpoint was for the lower bound of the 95% CI of vaccine
efficacy to be greater than 25%. Analysis was by intention to treat and per procotol. This trial is
registered with ClinicalTrials.gov, number NCT01373281.

FINDINGS: We randomly assigned 10 275 children to receive either vaccine (n=6851) or placebo
(n=3424), of whom 6710 (98%) and 3350 (98%), respectively, were included in the primary analysis.
250 cases of virologically confirmed dengue took place more than 28 days after the third injection
(117 [47%] in the vaccine group and 133 [53%] in the control group). The primary endpoint was
achieved with 56·5% (95% CI 43·8-66·4) efficacy. We recorded 647 serious adverse events
(402 [62%] in the vaccine group and 245 [38%] in the control group). 54 (1%) children in the
vaccine group and 33 (1%) of those in the control group had serious adverse events that happened
within 28 days of vaccination. Serious adverse events were consistent with medical disorders in this
age group and were mainly infections and injuries.

INTERPRETATION: Our findings show that dengue vaccine is efficacious when given as three
injections at months 0, 6, and 12 to children aged 2-14 years in endemic areas in Asia, and has a
good safety profile. Vaccination could reduce the incidence of symptomatic infection and hospital
admission and has the potential to provide an important public health benefit.

 

原文地址:

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61060-6/abstract

 

本站声明: 生物文库所有文章欢迎转载,所有文章未说明,均属于原创,转载均请注明出处。
本文链接: http://www.bioku.cn/201410/lancet-2014-10-11/
版权所有: 生物文库 - 生物医学、生物技术核心期刊文摘

留言


7 − 四 =


沪ICP备12028140号
点击这里给我发消息   点击这里给我发消息