The Effectiveness of Offering a 2nd Booster Dose of COVID-19 Vaccine on Preventing Severe COVID-19; A Register-based Randomized Trial (RRCT)
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 入组人数
- 600,000
- 主要终点
- Severe COVID-19
研究概览
简要总结
Background Recent studies indicate that a 2nd booster dose is associated with lower risk of severe COVID-19. The studies are based on Israeli registry data, comparing outcomes among individuals who have taken the booster, or not. Interpreting the findings from such non-experimental studies is challenging - there are likely systematic differences between those who accept the offer to take a booster dose, and those who do not.
Aim Determine the effect of offering vaccination with a 2nd COVID-19 booster dose on severe COVID-19, measured by hospitalization and death caused by COVID-19.
Methods Intervention group: A random sample drawn from the whole population aged 45-64 years with 3 doses of COVID-19 vaccine will receive a personal offer to receive the 4th dose of a COVID-19 vaccine in their municipality.
Control group: The rest of the population aged 45-64 with 3 doses, who will receive no such offer.
Randomization: The investigators will draw a set of birth dates - can then see who is in the intervention group in Beredt C19 (Norwegian emergency preparedness register for COVID-19) without identifying them individually (personal identification numbers are encrypted).
Primary outcome: Hospitalization or death caused by COVID-19 in a period of 10 weeks after invitations are sent.
Sample size calculations: 300 000 individuals in the intervention group, assuming risk of the primary outcome is at least 15% lower in the intervention group. (The investigators expect a large proportion NOT to accept the invitation to take the vaccine).
详细描述
Background and rationale
Several studies suggest a waning of COVID-19 vaccines' effectiveness over time, raising the question of whether booster doses should be offered to maintain protection against severe COVID-19.
Studies of the effectiveness of taking one booster dose, which for most people corresponds to a third vaccine dose, have shown promising results. Similarly, three recent studies examining the effectiveness of a 2nd booster dose found that the 2nd booster was associated with lower risk of severe COVID-19. All these studies are based on data from Israeli registries, comparing outcomes among individuals who have taken the booster, or not. Interpreting the findings from such non-experimental studies is challenging since there are likely systematic differences between those who accept the offer to take a booster dose, and those who do not. So called "healthy vaccinee bias" implies that those who take the vaccine are healthier than those not taking the vaccine. The opposite, however, may also be true: Those who perceive themselves to be more at risk may be more prone to accept the offer of vaccination. A related type of bias is the "premature efficacy bias" which is observed in many observational studies within one to two weeks after vaccination, probably due to people refraining from taking the vaccine if they suspect that they have already been infected. Comorbidities or socio-economic factors that are not adequately controlled for can also lead to biased results. The conventional approach to minimizing the risk of bias in effectiveness studies is to conduct a randomized trial - if feasible.
The future of the COVID-19 pandemic is unknown. In Norway, a large winter wave driven by the omicron variant of SARS-CoV-2 is receding after more than half the population has been infected. The vaccination coverage in the Norwegian population is also very high.
In the autumn of 2022, a new wave of infections may start due to waning immunity, and/or the emergence of a new variant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
We will, to the extent feasible, mask the data analysts to group allocation.
入排标准
- 年龄范围
- 45 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged between 45 and 64 years
- •Registered in the Norwegian national population register
- •Have received three doses of a COVID-19 vaccine, with the last dose received at least four months ago.
- •Have not previously been offered or recommended a 4th dose for medical reasons
排除标准
- •Persons who have already been offered a 4th COVID-19 vaccine dose.
- •Persons in whom COVID-19 vaccination is contraindicated as per the vaccines' Summary of Product Characteristics (SPC).
结局指标
主要结局
Severe COVID-19
时间窗: To be decided, but no more the 3 months
Hospitalization or death caused by COVID-19 starting on day 22 after the invitation is sent to the intervention group.
次要结局
- Health care utilization(10 weeks)
- Hospitalization or death(10 weeks)
- COVID-19 infection(10 weeks)
- Health care utilization related to potential side effects(10 weeks)
- Infection, hospitalization or death(12 months)