A Pragmatic Randomized Trial to Evaluate the Effect of Recombinant Herpes Zoster Vaccine on Major Adverse Cardiovascular Events and Dementia in Adults Aged 65 Years or Above
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 162,000
- 试验地点
- 2
- 主要终点
- Hospitalization for MACE
研究概览
简要总结
DAN-ZOSTER is a nationwide randomized study investigating whether vaccination against herpes zoster (shingles) can reduce the risk of cardiovascular disease and dementia in older adults. Herpes zoster is caused by reactivation of the varicella-zoster virus and becomes more common with increasing age. Some observational studies have suggested that vaccination against herpes zoster may also lower the risk of heart attacks, strokes, and dementia, but this has not been confirmed in randomized clinical trials.
In this study, approximately 162,000 adults aged 65 years or older living in Denmark will be randomly assigned to either receive the recombinant herpes zoster vaccine (Shingrix®) or receive no vaccine. Participants in the vaccine group will receive two doses given 2-6 months apart.
Participants will be identified and invited using Danish national registries and digital mail systems. Information about health outcomes will be collected through nationwide health registries during follow-up.
The main outcomes of the study are major cardiovascular events (heart attack, stroke, or cardiovascular death) and new diagnoses of dementia. The goal of the study is to determine whether herpes zoster vaccination can help prevent these conditions in older adults.
详细描述
Herpes zoster is caused by reactivation of the varicella-zoster virus and becomes increasingly common with age. In addition to causing acute illness and postherpetic neuralgia, observational studies have suggested that herpes zoster infection may be associated with an increased risk of cardiovascular events and dementia. Some observational studies have also reported lower risks of these outcomes among individuals vaccinated against herpes zoster. However, these findings may be affected by confounding, and randomized evidence is currently lacking.
The DAN-ZOSTER trial is a nationwide pragmatic randomized clinical trial designed to evaluate whether vaccination with the recombinant herpes zoster vaccine (Shingrix®) reduces the risk of major adverse cardiovascular events (MACE) and incident dementia in older adults.
In this open-label trial, approximately 162,000 adults aged 65 years or older will be randomized in a 1:1 ratio to receive the recombinant herpes zoster vaccine or no intervention. Participants randomized to the intervention arm will receive two intramuscular doses of Shingrix® administered 2-6 months apart. Participants randomized to the control arm will receive no study vaccination.
Outcomes and follow-up data will be obtained through linkage with Danish nationwide health registries.
The trial has two dual-primary outcomes: (1) major adverse cardiovascular events, defined as a composite of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death, and (2) incident dementia, defined as Alzheimer's disease, vascular dementia, or unspecified dementia. The study uses an event-driven design with predefined minimum follow-up requirements for each primary outcome.
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
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 65 years and above at the time of consent
- •Self-reported ability to understand written and spoken Danish or English
- •Informed consent form has been signed and dated
排除标准
- •The study has the following exclusion criteria which will be assessed through self-reporting:
- •A prior diagnosis of dementia
- •Chronic inflammatory rheumatic disease and concomitant immunosuppressive therapy
- •Prior herpes zoster vaccination
研究组 & 干预措施
No Herpes Zoster vaccine (control)
Control arm, no intervention.
Recombinant Herpes Zoster Vaccine (Shingrix).
干预措施: Recombinant Herpes Zoster Vaccine (Shingrix) (Biological)
结局指标
主要结局
Hospitalization for MACE
时间窗: From the first of the two initially booked study visits up to approximately 1 year
Defined as a composite of non-fatal myocardial infarction, non-fatal stroke and cardiovascular death
New dementia
时间窗: From the first of the two initially booked study visits up to approximately 3 years
Defined as a composite of Alzheimer's dementia, vascular dementia and unspecified dementia
次要结局
- Hospitalization for myocardial infarction(From the first of the two initially booked study visits up to approximately 1 year)
- Cardiovascular death(From the first of the two initially booked study visits up to approximately 1 year)
- Inpatient and/or outpatient diagnosis of Alzheimer's dementia(From the first of the two initially booked study visits up to approximately 3 years)
- Inpatient and/or outpatient diagnosis of vascular dementia(From the first of the two initially booked study visits up to approximately 3 years)
- Inpatient and/or outpatient diagnosis of unspecified dementia(From the first of the two initially booked study visits up to approximately 3 years)
- Hospitalization for non-fatal acute coronary syndrome, non-fatal stroke, or cardiovascular death(From the first of the two initially booked study visits up to approximately 1 year)
- Hospitalization for any cardiovascular disease(From the first of the two initially booked study visits up to approximately 1 year)
- Hospitalization for stroke(From the first of the two initially booked study visits up to approximately 1 year)
研究者
Tor Biering-Sørensen
Professor
Herlev and Gentofte Hospital