Cheuvart Brigitte, Friedland Leonard R, Abu-Elyazeed Remon, Han Htay Htay, Guerra Yolanda, Verstraeten Thomas
GlaxoSmithKline Biologicals, Rixensart, Belgium.
Pediatr Infect Dis J. 2009 Mar;28(3):225-32. doi: 10.1097/INF.0b013e31819715fa.
An oral, live attenuated human rotavirus vaccine, RIX4414 has been developed to prevent rotavirus gastroenteritis. An integrated safety summary of 8 randomized, placebo-controlled, double-blind phase II and III trials of vaccine at potency licensed for use worldwide was performed.
Healthy 1- to 18-week-old infants (N = 71209) were enrolled to receive 2 doses of RIX4414/placebo according to 0, 1 or 0, 2 month schedules. Solicited (fever, fussiness/irritability, loss of appetite, vomiting, diarrhea, cough/rhinorrhea) and unsolicited adverse events (AEs) were recorded for 8 days and 31 days, respectively, after each dose. Serious adverse events (SAEs) including intussusception and death were collected throughout the entire study periods. Potential imbalances were defined as the 95% confidence interval (CI) for the relative risk (RR) stratified by trials excluding "1."
Solicited AEs were evaluated in 3286 RIX4414 vaccinees and 2015 placebo recipients. Among solicited AEs, no imbalance was noted between groups. SAEs, including death and intussusception, were evaluated in 36755 RIX4414 and 34454 placebo recipients. Within 31 days after each dose, no imbalances were noted between the groups for all SAEs (RR = 0.9; 95% CI: 0.81, 1.01), deaths (RR = 1.64; 95% CI: 0.92, 3.02), and intussusception (RR 1.23; 95% CI: 0.41, 3.90). SAEs because of gastrointestinal diseases including diarrhea, gastroenteritis (all cause and due to rotavirus), dehydration, and intestinal ileus occurred significantly less often in RIX4414 than placebo recipients.
Across the phase II and III clinical trials, the reactogenicity and safety profile between RIX4414 and placebo was similar, in particular with no increased risk of intussusception.
一种口服减毒活人类轮状病毒疫苗RIX4414已被研发用于预防轮状病毒肠胃炎。对8项随机、安慰剂对照、双盲的II期和III期试验进行了综合安全性总结，这些试验使用的疫苗效力已在全球范围内获得许可。
纳入健康的1至18周龄婴儿（N = 71209），按照0、1月或0、2月的接种程序接受2剂RIX4414/安慰剂。在每次接种后，分别记录8天和31天内的主动（发热、烦躁/易怒、食欲不振、呕吐、腹泻、咳嗽/流涕）和被动不良事件（AE）。在整个研究期间收集包括肠套叠和死亡在内的严重不良事件（SAE）。潜在的不均衡定义为排除“1”的试验按相对风险（RR）分层的95%置信区间（CI）。
在3286名接种RIX4414疫苗者和2015名接受安慰剂者中评估了主动AE。在主动AE中，两组之间未发现不均衡。在36755名接种RIX4414者和34454名接受安慰剂者中评估了包括死亡和肠套叠在内的SAE。在每次接种后的31天内，所有SAE（RR = 0.9；95% CI：0.81，1.01）、死亡（RR = 1.64；95% CI：0.92，3.02）和肠套叠（RR 1.23；95% CI：0.41，3.90）的组间均未发现不均衡。与接受安慰剂者相比，RIX44疫苗接种者中因包括腹泻、肠胃炎（所有病因及轮状病毒所致）、脱水和肠梗阻在内的胃肠道疾病导致的SAE发生频率显著更低。
在II期和III期临床试验中，RIX4414与安慰剂之间的反应原性和安全性概况相似，尤其是肠套叠风险未增加。
