Effect of Recombinant Varicella Zoster Virus Glycoprotein E Vaccine on Major Adverse Cardiovascular Events and Dementia in Adults Aged 65 Years or Older

The primary objectives of this study are to evaluate the efficacy of the recombinant herpes zoster vaccine in reducing the risk of major adverse cardiovascular events (MACE), defined as a composite of hospitalization for non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, as well as the risk of new dementia in adults aged 65 years or older.

• Secondary objectives related to MACE include assessing the risk of a composite of hospitalization for non-fatal acute coronary syndrome, non-fatal stroke, or cardiovascular death; hospitalization for any cardiovascular disease; hospitalization for stroke; hospitalization for myocardial infarction; and cardiovascular death.
• Secondary objectives related to dementia include evaluating the risk of Alzheimer’s dementia, vascular dementia, and unspecified dementia.

The sponsor did not provide information regarding the total number of participants. The study population consists of healthy volunteers, including both males and females, aged 65 years and older. Participants must be able to understand written and spoken Danish or English and provide signed informed consent. The objectives are to evaluate the effect of Shingrix on the risk of major adverse cardiovascular events, which is a composite of hospitalization for non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, and to evaluate the effect on the risk of new dementia.

This pragmatic randomized controlled trial is designed to evaluate the effect of a recombinant herpes zoster vaccine on the risk of major adverse cardiovascular events (MACE) and new dementia in adults aged 65 years or older. The study utilizes a comparison between the administered vaccine and no vaccine to assess dual primary time-to-event endpoints, specifically hospitalization for MACE and the onset of new dementia. Secondary endpoints include composites of non-fatal acute coronary syndrome, non-fatal stroke, cardiovascular death, and various types of dementia such as Alzheimer’s dementia and vascular dementia. The clinical trial is estimated to occur between March 2026 and March 2029.

The experimental treatment consists of Shingrix, a recombinant, adjuvanted herpes zoster vaccine. The active substance is recombinant varicella zoster virus glycoprotein E. This medication is administered as a suspension for injection via intramuscular injection at a dosage of 0.5 mg.

The efficacy of the recombinant Herpes Zoster vaccine is assessed through dual primary time-to-event endpoints. These primary endpoints consist of hospitalization for Major Adverse Cardiovascular Events (MACE) and the incidence of new dementia in adults aged 65 years or older.

Secondary endpoints are categorized based on the primary objectives. MACE-related secondary endpoints include:

• A composite of hospitalization for non-fatal acute coronary syndrome, non-fatal stroke, or cardiovascular death
• Hospitalization for any cardiovascular disease
• Hospitalization for myocardial infarction

• Alzheimer’s dementia
• Vascular dementia
• Unspecified dementia