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NCT Number: NCT07485283

Recombinant Herpes Zoster Vaccine for Prevention of Cardiovascular Events and Dementia

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.

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Key information

Conditions

Cardiovascular Disease Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders DNA Virus Infections Dementia Heart Diseases Herpes Zoster Herpesviridae Infections Infarction Infections Ischemia Mental Disorders Myocardial Infarction Myocardial Ischemia Necrosis Nervous System Diseases Neurocognitive Disorders Pathologic Processes Pathological Conditions, Signs and Symptoms Stroke Varicella Zoster Virus Infection Vascular Diseases Virus Diseases

Age range

65 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

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

Treatment and study plan

Recombinant Herpes Zoster Vaccine (Shingrix)

Biological

Two doses of Shingrix vaccine spaced 2-6 months apart.

Primary outcomes

  1. Hospitalization for MACE

    Time frame: 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

  2. New dementia

    Time frame: 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

Secondary outcomes

  1. 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

    Defined as a composite of acute coronary syndrome, stroke and cardiovascular death

    Any I-diagnosis as cause of death

  2. Hospitalization for any cardiovascular disease

    Time frame: From the first of the two initially booked study visits up to approximately 1 year

  3. Hospitalization for stroke

    Time frame: From the first of the two initially booked study visits up to approximately 1 year

  4. Hospitalization for myocardial infarction

    Time frame: From the first of the two initially booked study visits up to approximately 1 year

  5. Cardiovascular death

    Time frame: From the first of the two initially booked study visits up to approximately 1 year

  6. 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

  7. 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

  8. 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

Other outcomes

  1. Hospitalization for unstable angina

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  2. Acute and/or elective coronary revascularization

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  3. Hospitalization for heart failure

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  4. Hospitalization for pulmonary embolism

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  5. Hospitalization for deep venous thrombosis

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  6. Combined endpoint of deep venous thrombosis and hospitalization for pulmonary embolism

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  7. Hospitalization for a combined end point of acute coronary syndrome, stroke, heart failure and cardiovascular death

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  8. New heart failure

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  9. Hospitalization for ischemic stroke

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  10. Hospitalization for hemorrhagic stroke

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  11. Transient ischemic attack

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  12. Hospitalization for atrial fibrillation

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  13. New atrial fibrillation

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  14. Hospitalization for pericarditis

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  15. Hospitalization for myocarditis

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  16. Hospitalization for endocarditis

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  17. Hospitalization for cardiovascular causes

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  18. All-cause hospitalization

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  19. All-cause death

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  20. Inpatient and/or outpatient diagnosis of new dementia or cognitive impairment

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  21. Inpatient and/or outpatient diagnosis of frontotemporal dementia

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  22. Hospitalization with delirium

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  23. Hospitalization for Herpes Zoster

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  24. Hospitalization for influenza

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  25. Laboratory-confirmed influenza infection

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

  26. Hospitalization for an infectious disease

    Time frame: From the first of the two initially booked study visits up to approximately 3 years

Study contacts

Contact information is provided by the study sponsor or research team.

Daniel Modin, MD

CONTACT

[email protected]

+4541828993

Tor Biering-Sørensen, MD, PhD, MSc, MPH

CONTACT

[email protected]

+4528933590

Sponsors and collaborators

Lead sponsor

Tor Biering-Sørensen

Other

Collaborators

  • GlaxoSmithKline

Registry information

Official study title

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

Acronym: DAN-ZOSTER

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Mar 20, 2026
Registry last updated
May 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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