An open-label randomized clinical trial of prophylactic paracetamol coadministered with 7-valent pneumococcal conjugate vaccine and hexavalent diphtheria toxoid, tetanus toxoid, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine
An open-label randomized clinical trial of prophylactic paracetamol coadministered with 7-valent pneumococcal conjugate vaccine and hexavalent diphtheria toxoid, tetanus toxoid, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine
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DOI：
10.1186/1471-2431-13-98
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发表时间：
2013-06-21
期刊：
影响因子：
2.4
通讯作者：
Zielen, Stefan
中科院分区：
文献类型：
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作者：
Rose, Markus A.;Juergens, Christine;Zielen, Stefan
背景：在两项临床试验中，与单独接种两种推荐的常规儿科疫苗相比，联合接种后出现低烧的频率更高。由于发热是疫苗耐受性的一个重要问题，我们在德国进行了这项开放标签研究，研究了在接种常规7价肺炎球菌结合疫苗（PCV-7）和六价疫苗（白喉-破伤风-无细胞百日咳-乙型肝炎，脊髓灰质炎病毒，流感嗜血杆菌B型疫苗[DTPa-HBV-IPV/Hib]）的儿童中预防性使用扑热息痛（对乙酰氨基酚，贝能龙(R)）的有效性和安全性。方法：健康婴儿（N = 301）接受了PCV-7和DTPa-HBV-IPV/Hib 3剂婴儿系列疫苗加上幼儿剂量，在接种疫苗时随机按1:1分配预防性扑热息痛（125 mg或250 mg栓剂，基于体重），之后每隔6-8小时，或对照组不接受扑热息痛。接种疫苗后4天测量直肠温度和局部及其他全身反应；在整个研究过程中收集不良事件。结果：在打算治疗的人群中，扑热息痛降低了发烧的发生率，但这种降低仅对婴儿系列有意义，计算的疗效为43.0%(95%置信区间[CI]: 17.4, 61.2)，在幼儿剂量后不显著（疗效15.9%;95% CI: -19.9, 41.3）；每个方案（PP）人群的结果相似。在婴儿系列中，发烧低于39摄氏度是罕见的，因此病例太少，无法评估。在幼儿给药后，扑热息痛有效地降低了体温（0 ~ 39℃），仅在PP人群中达到统计学意义（有效率79%；95% CI: 3.9, 97.7）。扑热息痛也能降低反应原性，但在任何剂量后各组之间没有显著差异。未报告与疫苗相关的严重不良事件。结论：扑热息痛可有效预防发热及其他反应，主要发生在婴幼儿期。然而，由于两组的事件一般都是轻微的，没有引起关注，我们的数据支持目前的建议，即仅使用扑热息痛治疗症状，而不是常规预防。试验注册：NCT00294294
Background: In two clinical trials, low-grade fever was observed more frequently after coadministration than after separate administration of two recommended routine pediatric vaccines. Since fever is an important issue with vaccine tolerability, we performed this open-label study on the efficacy and safety of prophylactic use of paracetamol (acetaminophen, Benuron (R)) in children administered routine 7-valent pneumococcal conjugate vaccine (PCV-7) coadministered with hexavalent vaccine (diphtheria-tetanus-acellular pertussis-hepatitis B, poliovirus, Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]) in Germany.Methods: Healthy infants (N = 301) who received a 3-dose infant series of PCV-7 and DTPa-HBV-IPV/Hib plus a toddler dose were randomly assigned 1:1 to prophylactic paracetamol (125 mg or 250 mg suppositories, based on body weight) at vaccination, and at 6-8 hour intervals thereafter, or a control group that received no paracetamol. Rectal temperature and local and other systemic reactions were measured for 4 days post vaccination; adverse events were collected throughout the study.Results: In the intent-to-treat population, paracetamol reduced the incidence of fever >= 38 degrees C, but this reduction was only significant for the infant series, with computed efficacy of 43.0% (95% confidence interval [CI]: 17.4, 61.2), and not significant after the toddler dose (efficacy 15.9%; 95% CI: -19.9, 41.3); results were similar in the per protocol (PP) population. Fever >39 degrees C was rare during the infant series, such that there were too few cases for assessment. After the toddler dose, paracetamol effectively reduced fever >39 degrees C, reaching statistical significance in the PP population only (efficacy 79%; 95% CI: 3.9, 97.7). Paracetamol also reduced reactogenicity, but there were few significant differences between groups after any dose. No vaccine-related serious adverse events were reported.Conclusions: Paracetamol effectively prevented fever and other reactions, mainly during the infant series. However, as events were generally mild and of no concern in either group our data support current recommendations to administer paracetamol to treat symptoms only and not for routine prophylaxis. Trial registration: NCT00294294