Recombinant Herpes Zoster Vaccine for Prevention of Cardiovascular Events and Dementia (DAN-ZOSTER)

April 28, 2026 updated by: Tor Biering-Sørensen

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

162000

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Hellerup, Denmark, 2900
        • Not yet recruiting
        • Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte
        • Contact:
        • Principal Investigator:
          • Tor Biering-Sørensen
      • Søborg, Denmark
        • Recruiting
        • Danske Lægers Vaccinations Service
        • Principal Investigator:
          • Carsten Schade Larsen, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Age 65 years and above at the time of consent
  2. Self-reported ability to understand written and spoken Danish or English
  3. Informed consent form has been signed and dated

Exclusion Criteria:

The study has the following exclusion criteria which will be assessed through self-reporting:

  1. A prior diagnosis of dementia
  2. Chronic inflammatory rheumatic disease and concomitant immunosuppressive therapy
  3. Prior herpes zoster vaccination

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Recombinant Herpes Zoster Vaccine (Shingrix).
Biological: Recombinant Herpes Zoster Vaccine (Shingrix)
Two doses of Shingrix vaccine spaced 2-6 months apart.
No Intervention: No Herpes Zoster vaccine (control)
Control arm, no intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From the first of the two initially booked study visits up to approximately 1 year
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
From the first of the two initially booked study visits up to approximately 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
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
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
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
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
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
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
From the first of the two initially booked study visits up to approximately 3 years

Other Outcome Measures

Outcome Measure
Time Frame
Hospitalization for unstable angina
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Acute and/or elective coronary revascularization
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization for heart failure
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization for pulmonary embolism
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization for deep venous thrombosis
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
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
From the first of the two initially booked study visits up to approximately 3 years
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
From the first of the two initially booked study visits up to approximately 3 years
New heart failure
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization for ischemic stroke
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization for hemorrhagic stroke
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Transient ischemic attack
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization for atrial fibrillation
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
New atrial fibrillation
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization for pericarditis
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization for myocarditis
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization for endocarditis
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization for cardiovascular causes
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
All-cause hospitalization
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
All-cause death
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
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
From the first of the two initially booked study visits up to approximately 3 years
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
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization with delirium
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization for Herpes Zoster
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization for influenza
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Laboratory-confirmed influenza infection
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years
Hospitalization for an infectious disease
Time Frame: From the first of the two initially booked study visits up to approximately 3 years
From the first of the two initially booked study visits up to approximately 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tor Biering-Sørensen

Collaborators

GlaxoSmithKline

Investigators

  • Study Chair: Tor Biering-Sørensen, MD, PhD, MSc, MPH, Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 28, 2026

Primary Completion (Estimated)

April 1, 2029

Study Completion (Estimated)

April 1, 2029

Study Registration Dates

First Submitted

March 8, 2026

First Submitted That Met QC Criteria

March 16, 2026

First Posted (Actual)

March 20, 2026

Study Record Updates

Last Update Posted (Actual)

May 4, 2026

Last Update Submitted That Met QC Criteria

April 28, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAN-ZOSTER
  • 2025-524944-37-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

In this trial, baseline and endpoint data will be collected from Danish administrative health registries, which are subject to Danish legislation and can only be made available to a third party under certain conditions. Please contact the sponsor-investigator in case of any inquiries.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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