AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial
AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial
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DOI：
10.1016/s1473-3099(13)70046-x
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发表时间：
2013-06-01
影响因子：
56.3
通讯作者：
Oostvogels, Lidia
中科院分区：
文献类型：
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作者：
McElhaney, Janet E.;Beran, Jiri;Oostvogels, Lidia
背景我们的目的是比较AS03佐剂灭活三价流感疫苗（TIV）与非佐剂TIV预防老年人季节性流感的效果。方法我们在2008 - 09年（第1年）和2009 - 10年（第2年）流感季节在全球15个国家进行了一项随机试验。年龄至少65岁、未住院或卧床不起且无急性疾病的合格受试者被随机分配（1：1）接受含AS03佐剂的TIV或无佐剂的TIV。在基于互联网的系统中进行随机化，采用区组方案并按年龄分层（65 - 74岁和75岁或以上）。参与者计划每年接种一次疫苗，并在第1年和第2年保持在同一组。未设盲的人员准备并接种疫苗，但参与者和评估任何研究终点的个人均被设盲。共同主要目的是评估疫苗的相对有效性和AS03佐剂TIV的批间一致性（将在其他地方报告）。对于第一个目的，主要终点是疫苗预防甲型流感（不包括甲型H1N1 pdm09）或B或两者的相对有效性，这在第1年通过PCR分析得到证实（双侧95% CI的下限必须大于零，以确定优效性）。从11月15日到4月30日，在这两年中，参与者每周或每两周通过电话或现场联系和家访进行监测，以确定流感样疾病病例。在疑似病例发病后，我们获得了鼻和咽拭子，以实时PCR鉴定流感RNA。根据方案进行疗效分析。该试验在www.example.com注册，编号为NCT 00753272。结果我们招募了43802名参与者，其中21893名参与者在第1年被分配并接受了含AS03佐剂的TIV，21802名参与者接受了无佐剂的TIV。在第1年疗效队列中，与无佐剂TIV相比，接受AS 03佐剂治疗的受试者感染甲型流感或B流感或两者均感染的受试者较少（21573例中274例[1.27%，95% CI 1.12 - 1.43] vs 21482例中310例[1.44%，1.29 - 1.61];相对有效性12 - 11%，95% CI-3.40至25.29;未确立优效性）。在第1年疗效队列中，与非佐剂TIV相比，接受AS03佐剂TIV的受试者感染甲型流感的人数较少（224 [1.04%，95% CI 0.91 - 1.18] vs 270 [1 26，1.11 - 1.41];相对有效性17.53%，95% CI 1.55 - 30.92）和甲型流感H3N2（170 [0.79，0.67 - 0.92] vs 205 [0.95，0.83 - 1.09];事后分析相对有效性22.0%，解释AS03佐剂化的TIV对于预防流感的一些亚型具有比非佐剂化的TIV更高的功效。未来在老年人中进行的流感疫苗研究应基于亚型或谱系特异性终点。
Background We aimed to compare AS03-adjuvanted inactivated trivalent influenza vaccine (TIV) with non-adjuvanted TIV for seasonal influenza prevention in elderly people.Methods We did a randomised trial in 15 countries worldwide during the 2008-09 (year 1) and 2009-10 (year 2) influenza seasons. Eligible participants aged at least 65 years who were not in hospital or bedridden and were without acute illness were randomly assigned (1:1) to receive either AS03-adjuvanted TIV or non-adjuvanted TIV. Randomisation was done in an interne-based system, with a blocldng scheme and stratification by age (65-74 years and 75 years or older). Participants were scheduled to receive one vaccine in each year, and remained in the same group in years 1 and 2. Unmasked personnel prepared and gave the vaccines, but participants and individuals assessing any study endpoint were masked. The coprimary objectives were to assess the relative efficacy of the vaccines and lot-to-lot consistency of the AS03-adjuvanted TIV (to be reported elsewhere). For the first objective, the primary endpoint was relative efficacy of the vaccines for prevention of influenza A (excluding A H1N1 pdm09) or B, or both, that was confirmed by PCR analysis in year 1 (lower limit of two-sided 95% CI had to be greater than zero to establish superiority). From Nov 15, to April 30, in both years, participants were monitored by telephone or site contact and home visits every week or 2 weeks to identify cases of influenza-like illness. After onset of suspected cases, we obtained nasal and throat swabs to identify influenza RNA with real-time PCR. Efficacy analyses were done per protocol. This trial is registered with ClinicalTrials.gov, number NCT00753272.Findings We enrolled 43802 participants, of whom 21893 were assigned to and received the AS03-adjuvanted TIV and 21802 the non-adjuvanted TIV in year 1. In the year 1 efficacy cohort, fewer participants given AS03-adjuvanted than non-adjuvanted TIV were infected with influenza A or B, or both (274 [1.27%, 95% CI 1.12-1.43] of 21573 vs 310 [1.44%, 1.29-1.61] of 21482; relative efficacy 12-11%, 95% CI -3.40 to 25.29; superiority not established). Fewer participants in the year 1 efficacy cohort given AS03-adjuvanted TIV than non-adjuvanted TIV were infected with influenza A (224 [1.04%, 95% CI 0.91-1.18] vs 270 [1 26, 1.11-1.41]; relative efficacy 17.53%, 95% CI 1.55-30.92) and influenza A H3N2 (170 [0.79, 0.67-0.92] vs 205 [0 95, 0.83-1.09]; post-hoc analysis relative efficacy 22.0%, 95% CI 5.68-35.49).Interpretation AS03-adjuvanted TIV has a higher efficacy for prevention of some subtypes of influenza than does a non-adjuvanted TIV. Future influenza vaccine studies in elderly people should be based on subtype or lineage-specific endpoints.