University Medical Center, Utrecht, The Netherlands.
Radboud University Medical Center, Nijmegen, the Netherlands.
Trials. 2020 Jun 5;21(1):481. doi: 10.1186/s13063-020-04389-w.
The objectives of these two separate trials are: (1) to reduce health care workers (HCWs) absenteeism; and (2) to reduce hospital admission among the elderly during the COVID-19 pandemic through BCG vaccination.
Two separate multi-centre placebo-controlled parallel group randomized trials PARTICIPANTS: (1) Health care personnel working in the hospital or ambulance service where they will take care of patients with the COVID-19 infection and (2) elderly ≥60 years. The HCW trial is being undertaken in 9 hospitals. The elderly trial is being undertaken in locations in the community in Nijmegen, Utrecht, and Veghel, in the Netherlands, using senior citizen organisations to facilitate recruitment.
For both trials the intervention group will be randomized to vaccination with 0.1 ml of the licensed BCG vaccine (Danish strain 1331, SSI, Denmark, equivalent to 0.075 mg attenuated M. bovis). The placebo group consists of 0.1 ml 0.9% NaCl, which is the same amount, and has the same colour and appearance as the suspended BCG vaccine.
(1) Number of days of unplanned work absenteeism in HCWs for any reason which can be continuously measured on a bi-weekly basis, and (2) the cumulative incidence of hospital admission due to documented COVID-19.
Participants will be randomized to BCG vaccine or placebo (1;1) centrally using a computer- based system, stratified by study centre.
BLINDING (MASKING): Subjects, investigators, physicians and outcome assessors are blinded for the intervention. Only the pharmacist assistant that prepares- and research personnel that administers- study medicines are unblinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): (1) The sample size for the first trial is N=1500 HCWs randomised 1:1 to either BCG vaccine (n=750) and placebo (n=750) and (2) The sample size for the second trial is N=1600 elderly persons randomised to BCG vaccine (n=800) and the placebo group (n=800).
HCW: version 4.0, 24-04-2020. Recruitment began 25-03-2020 and was completed on the 23-04-2020. Elderly: version 3.0, 04-04-2020. Recruitment began 16-04- 2020 and is ongoing.
The HCWs trial was registered 31-03-2020 at clinicaltrials.gov (identifier: NCT04328441) and registered 20-03-2020 at the Dutch Trial Registry (trialregister.nl, identifier Trial NL8477). The elderly trial was registered 22-04-2020 at the Dutch trial registry with number NL8547.
The full protocols will be attached as additional files, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
这两项独立试验的目的是：(1)减少医护人员（HCWs）旷工；(2)通过卡介苗（BCG）接种减少 COVID-19 大流行期间老年人的住院人数。
两项独立的多中心安慰剂对照平行组随机试验
(1)在医院或救护服务机构工作的医护人员，他们将负责照顾 COVID-19 感染患者；(2)年龄≥60 岁的老年人。HCW 试验在 9 家医院进行。老年人试验在荷兰奈梅亨、乌得勒支和 Veghel 的社区场所进行，利用老年组织促进招募。
对于这两项试验，干预组将随机接种 0.1 毫升许可的 BCG 疫苗（丹麦菌株 1331，SSI，丹麦，相当于 0.075 毫克减毒牛分枝杆菌）。安慰剂组由 0.1 毫升 0.9%生理盐水组成，数量相同，颜色和外观与悬浮 BCG 疫苗相同。
(1)HCWs 因任何原因无计划旷工的天数，可以每两周连续测量一次；(2)因有记录的 COVID-19 而住院的累积发生率。
参与者将使用基于计算机的系统在中央以 1:1 的比例随机分配到 BCG 疫苗或安慰剂（1:1），按研究中心分层。
盲法（掩蔽）：研究对象、研究人员、医生和结果评估者对干预措施进行盲法。只有准备和管理研究药物的药剂师助手和研究人员是不盲的。随机分组数量（样本量）：(1)第一项试验的样本量为 N=1500 名随机 1:1 接种 BCG 疫苗（n=750）和安慰剂（n=750）的 HCWs；(2)第二项试验的样本量为 N=1600 名老年人随机接种 BCG 疫苗（n=800）和安慰剂组（n=800）。
HCW：第 4.0 版，2020 年 4 月 24 日。招募于 2020 年 3 月 25 日开始，并于 2020 年 4 月 23 日完成。老年人：第 3.0 版，2020 年 4 月 4 日。招募于 2020 年 4 月 16 日开始，正在进行中。
HCWs 试验于 2020 年 3 月 31 日在 clinicaltrials.gov 注册（标识符：NCT04328441），并于 2020 年 3 月 20 日在荷兰试验登记处（trialregister.nl，标识符试验 NL8477）注册。老年人试验于 2020 年 4 月 22 日在荷兰试验登记处注册，编号为 NL8547。
完整方案将作为附加文件附加，可从试验网站访问（附加文件 1）。为了加快传播这一材料，已删除熟悉的格式；本函作为完整方案的主要内容摘要。
