Recombinant Herpes Zoster Vaccine for Prevention of Cardiovascular Events and Dementia

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.

• Hospitalization for non-fatal acute coronary syndrome, non-fatal stroke, or cardiovascular death [Time frame: From the first of the two initially booked study visits up to approximately 1 year]
• Hospitalization for any cardiovascular disease [Time frame: From the first of the two initially booked study visits up to approximately 1 year]
• Hospitalization for stroke [Time frame: From the first of the two initially booked study visits up to approximately 1 year]
• Hospitalization for myocardial infarction [Time frame: From the first of the two initially booked study visits up to approximately 1 year]
• Cardiovascular death [Time frame: From the first of the two initially booked study visits up to approximately 1 year]
• Inpatient and/or outpatient diagnosis of Alzheimer's dementia [Time frame: From the first of the two initially booked study visits up to approximately 3 years]
• Inpatient and/or outpatient diagnosis of vascular dementia [Time frame: From the first of the two initially booked study visits up to approximately 3 years]
• Inpatient and/or outpatient diagnosis of unspecified dementia [Time frame: From the first of the two initially booked study visits up to approximately 3 years]