Servicio de Prevención de Riesgos Laborales, Complejo Asistencial Universitario de Salamanca, Salamanca, Spain.
Servicio de Prevención de Riesgos Laborales, Complejo Asistencial Universitario de Salamanca, Salamanca, Spain.
Vaccine. 2021 Jan 15;39(3):554-563. doi: 10.1016/j.vaccine.2020.12.006. Epub 2020 Dec 15.
An interventional, phase 4, single group assignment, without masking (open label), preventive clinical trial was carried out in health workers with biological risk in their tasks, who have been filed as non-responders to conventional vaccination against Hepatitis B.
67 health workers with biological risk in their tasks, who have been filed as non-responders to conventional vaccination against Hepatitis B, were enrolled in the Clinical Trial. All participants were from 18 years up to 64 years old.
NHS workers -including university students doing their internships in health centres dependent on the National Health System (inclusion of students is regulated and limited by specific instructions on labour prevention in each autonomous community)- classified as non-responders. The criteria defining them as non-responders to the conventional hepatitis B vaccine is anti HBsAb titers < 10 mUI/ml following the application of six doses of conventional vaccine at 20 μg doses (two complete guidelines). The objective of this study was to provide Health workers-staff with an additional protection tool against hepatitis B infection, and to evaluate the efficacy of the adjuvanted vaccine in healthy non-responders to conventional hepatitis B vaccine. The primary outcome was the measurement of antibody antiHBs before the first Fendrix® dose and a month after the administration of each dose. Other outcome was collection of adverse effects during administration and all those that could be related to the vaccine and that occur within 30 days after each dose. In this study, only one group was assigned. There was no randomization or masking.
The participants were recruited between April 13, 2018 and October 31, 2019. 67 participants were enrolled in the Clinical Trial and included the analyses. The primary immunisation consists of 4 separate 0.5 ml doses of Fendrix®, administered at the following schedule: 1 month, 2 months and 6 months from the date of the first dose. Once the positivity was reached in any of the doses, the participant finished the study and was not given the following doses. 68.66% (46 out 67) had a positive response to first dose of Fendrix®. 57.14% (12 out 21) had a positive response to second dose of Fendrix®. 22.22% (2 out 9) had a positive response to third dose of Fendrix and 42.96% (3 out 7) had a positive response to last dose of Fendrix®. Overall, 94.02% (64 out 67) of participants had a positive response to Fendrix®. No serious adverse event occurred.
The use of Fendrix®, is a viable vaccine alternative for NHS workers classified as "non-responders". Revaccination of healthy non-responders with Fendrix®, resulted in very high proportions of responders without adverse events.
The trial was registered in the Spanish National Trial Register (REEC), ClinicalTrials.gov and inclusion has been stopped (identifier NCT03410953; EudraCT-number 2016-004991-23).
GRS 1360/A/16: Call for aid for the financing of research projects in biomedicine, health management and socio-health care to be developed in the centres of the Regional Health Management of Autonomous Community of Castile-Leon. In addition, this work has been supported by the Spanish Platform for Clinical Research and Clinical Trials, SCReN (Spanish Clinical Research Network), funded by the Subdirectorate General for Research Evaluation and Promotion of the Carlos III Health Institute (ISCIII), through the project PT13/0002/0039 and project PT17/0017/0023 integrated in the State Plan for R&D&I 2013-2016 and co-financed by and the European Regional Development Fund (ERDF).
一项干预性、四期、单组分配、无掩蔽（开放标签）、预防性临床试验在有生物风险的卫生工作者中进行，这些工作者被归类为对乙型肝炎常规疫苗无反应者。
67 名有生物风险的卫生工作者被招募入组，这些工作者被归类为对乙型肝炎常规疫苗无反应者。所有参与者年龄在 18 岁至 64 岁之间。
NHS 工作人员-包括在国家卫生系统（NHS）下属的卫生中心实习的大学生（学生的纳入受到每个自治区特定劳动预防指令的限制和规范）-被归类为无反应者。无反应者的定义是接受 6 剂 20μg 剂量常规疫苗接种后，抗 HBsAb 滴度<10 mUI/ml。本研究的目的是为卫生工作者提供一种额外的乙型肝炎感染防护工具，并评估佐剂疫苗在健康的乙型肝炎常规疫苗无反应者中的疗效。主要结局是在第一次接种 Fendrix®前和每次接种后一个月测量抗 HBs 抗体。其他结局是在给药期间收集不良反应，以及所有与疫苗相关的、在每次给药后 30 天内发生的不良反应。在这项研究中，只分配了一组。没有随机化或掩蔽。
参与者于 2018 年 4 月 13 日至 2019 年 10 月 31 日期间招募。67 名参与者入组并进行了分析。初次免疫包括 4 剂 0.5ml 的 Fendrix®，接种计划如下：从第一剂日期起 1 个月、2 个月和 6 个月。任何一剂达到阳性后，参与者完成研究，不再接种后续剂量。68.66%（46 名/67 名）对第一剂 Fendrix®有阳性反应。57.14%（12 名/21 名）对第二剂 Fendrix®有阳性反应。22.22%（2 名/9 名）对第三剂 Fendrix 有阳性反应，42.96%（3 名/7 名）对最后一剂 Fendrix®有阳性反应。总体而言，94.02%（67 名/67 名）的参与者对 Fendrix®有阳性反应。没有发生严重不良事件。
Fendrix®是 NHS 工作人员“无反应者”的一种可行的疫苗替代方案。用 Fendrix®对健康的乙型肝炎常规疫苗无反应者进行再接种，导致很高比例的应答者，且无不良反应。
该试验在西班牙国家试验登记处（REEC）、ClinicalTrials.gov 注册，并已停止入组（标识符 NCT03410953；EudraCT 编号 2016-004991-23）。
GRS 1360/A/16：为在卡斯蒂利亚-莱昂自治区卫生管理中心开展的生物医学、卫生管理和社会卫生保健研究项目提供资金援助。此外，这项工作得到了西班牙临床研究和临床试验平台（SCReN）的支持，该平台由卡洛斯三世卫生研究所（ISCIII）下属的研究评估和促进总局资助，通过项目 PT13/0002/0039 和项目 PT17/0017/0023 进行，这些项目纳入了 2013-2016 年国家研发与创新计划，并由欧洲区域发展基金（ERDF）共同资助。
