Vaccine Effectiveness of a Bivalent RSV Prefusion F Protein-Based Vaccine for Preventing RSV Hospitalizations in Adults (DAN-RSV)

A Pragmatic Randomized Trial to Evaluate the Vaccine Effectiveness of Abrysvo® for Preventing RSV Hospitalizations in Adults Aged 18 Years or Above

The purpose of this pragmatic randomized trial is to evaluate the vaccine effectiveness of bivalent RSV prefusion F vaccine (RSV vaccine) in adults. Participants will be randomized 1:1 to either RSV vaccine or no RSV vaccine.

Study Overview

• Status: Active, not recruiting
• Conditions: RSV
• Intervention / Treatment: Biological: RSV prefusion F protein-based vaccine

Detailed Description

The study is a pragmatic, registry-based, open-label, individually randomized trial. Administrative health registries will be used for data collection including baseline information, follow-up data, and safety monitoring. The study aims to randomize a total of 690,000 participants. Participants will be individually randomized 1:1 to receive either a bivalent RSV prefusion F vaccine (RSV vaccine) or no RSV vaccine. The trial is designed to assess the vaccine effectiveness of the RSV vaccine vs. no RSV vaccine on RSV-related and all-cause cardio-respiratory outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 690000
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2900
    • Center for Translational Cardiology and Pragmatic Randomized Trials Department of Cardiology Copenhagen University Hospital - Herlev and Gentofte
  • Søborg, Denmark, 2860
    • Danske Lægers Vaccinations Service
• Spain
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain
      • General Public Health Directorate of Galician Health Service

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Age 18 years and above
• Informed consent form has been signed and dated

Exclusion Criteria:

• There are no specific exclusion criteria for this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RSV prefusion F protein-based vaccine (RSV vaccine); RSV vaccine single injection at day 0	Biological: RSV prefusion F protein-based vaccine; For this arm, the RSV prefusion F protein-based vaccine Abrysvo® will be used; Other Names: RSVpreF vaccine
No Intervention: No RSV vaccine (control); Control arm, no RSV vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hospitalization for RSV-related respiratory tract disease	≥14 days after initially booked vaccination/ information visit date up to 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RSV-related respiratory tract disease hospitalization	Primary outcome evaluated among the as-treated study population with balanced follow up time between study arms	≥14 days after actual vaccination date/ booked information visit date up to 8 months
Hospitalization for RSV-related lower respiratory tract disease		≥14 days after initially booked vaccination/ information visit date up to 8 months
RSV-related hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
All-cause respiratory tract disease hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
RSV-related cardio-respiratory hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
All-cause cardio-respiratory hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
All-cause lower respiratory tract disease hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
All-cause hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
All-cause mortality		≥14 days after initially booked vaccination/ information visit date up to 8 months
Hospitalization for RSV-related respiratory tract disease by age groups	Stratified by age groups (18-59, 60-74 years and 75+ years)	≥14 days after initially booked vaccination/ information visit date up to 8 months
RSV-related respiratory tract disease hospitalization (as-treated)	Among the as-treated study population with balanced follow up time between study arms	≥14 days after initially booked vaccination/ information visit date up to 8 months
Hospitalization for RSV-related respiratory tract disease in subsequent seasons	Subsequent seasons (2025/2026 and 2026/2027 RSV seasons)	From June 1, 2025 up to 12 months (2025/2026 season) and June 1, 2026 up to 12 months (2026/2027 season)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization for RSV-related respiratory tract disease stratified by RSV type	Stratification by RSV type (A or B)	≥14 days after initially booked vaccination/ information visit date up to 8 months
Total length of hospital stays due to respiratory tract infection with RSV infection		≥14 days after initially booked vaccination/ information visit date up to 8 months
RSV or pneumonia hospitalization [composite endpoint]	Based only on ICD-10 codes	≥14 days after initially booked vaccination/ information visit date up to 8 months
Pneumonia hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
Any hospitalization with RSV infection		≥14 days after initially booked vaccination/ information visit date up to 8 months
Cardiovascular disease hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
Hospitalization requiring mechanical ventilation		≥14 days after initially booked vaccination/ information visit date up to 8 months
Intensive care unit hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
Myocardial infarction hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
Heart failure hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
Stroke hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
Influenza hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
COVID-19 hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
Hospitalization for pneumococcal disease		≥14 days after initially booked vaccination/ information visit date up to 8 months
Any infectious disease hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
MACE (composite endpoint)	Non-fatal myocardial infarction, heart failure hospitalization, stroke, and cardiovascular death	≥14 days after initially booked vaccination/ information visit date up to 8 months
Laboratory-confirmed RSV infection		≥14 days after initially booked vaccination/ information visit date up to 8 months
Laboratory-confirmed influenza infection		≥14 days after initially booked vaccination/ information visit date up to 8 months
Laboratory-confirmed pneumococcal infection		≥14 days after initially booked vaccination/ information visit date up to 8 months
Laboratory-confirmed COVID-19 infection		≥14 days after initially booked vaccination/ information visit date up to 8 months
Cardio-respiratory mortality		≥14 days after initially booked vaccination/ information visit date up to 8 months
Respiratory mortality		≥14 days after initially booked vaccination/ information visit date up to 8 months
Cardiovascular mortality		≥14 days after initially booked vaccination/ information visit date up to 8 months
In-hospital mortality		≥14 days after initially booked vaccination/ information visit date up to 8 months
30-day mortality following hospital discharge for primary endpoint		≥14 days after initially booked vaccination/ information visit date up to 8 months
RSV-related respiratory tract disease hospitalization by chronic obstructive pulmonary disease status	Primary endpoint in patients with chronic obstructive pulmonary disease	≥14 days after initially booked vaccination/ information visit date up to 8 months
New-onset dementia		≥14 days after initially booked vaccination/ information visit date up to 10 years
RSV-related respiratory tract disease hospitalization by immunocompromised status	Stratified by immunocompromised status. Analysis will be carried out as outlined in C3761080, EU PASS register number EUPAS1000000480	≥14 days after initially booked vaccination/ information visit date up to 8 months
RSV-related lower respiratory tract disease hospitalization by immunocompromised status	Stratified by immunocompromised status. Analysis will be carried out as outlined in C3761080, EU PASS register number EUPAS1000000480	≥14 days after initially booked vaccination/ information visit date up to 8 months
All-cause respiratory tract disease hospitalization by immunocompromised status	Stratified by immunocompromised status. Analysis will be carried out as outlined in C3761080, EU PASS register number EUPAS1000000480	≥14 days after initially booked vaccination/ information visit date up to 8 months
All-cause lower respiratory tract disease hospitalization by immunocompromised status	Stratified by immunocompromised status. Analysis will be carried out as outlined in C3761080, EU PASS register number EUPAS1000000480	≥14 days after initially booked vaccination/ information visit date up to 8 months
RSV-related respiratory tract disease hospitalization by severe immunocompromised status	Stratified by severe immunocompromised status. Analysis will be carried out as outlined in C3761080, EU PASS register number EUPAS1000000480	≥14 days after initially booked vaccination/ information visit date up to 8 months
All-cause respiratory tract disease hospitalization by severe immunocompromised status	Stratified by severe immunocompromised status. Analysis will be carried out as outlined in C3761080, EU PASS register number EUPAS1000000480	≥14 days after initially booked vaccination/ information visit date up to 8 months
Atrial fibrillation hospitalization	Analysis will be carried out as outlined in C3761080, EU PASS register number EUPAS1000000480	≥14 days after initially booked vaccination/ information visit date up to 8 months
Hospitalization for any cardiac arrythmia	Analysis will be carried out as outlined in C3761080, EU PASS register number EUPAS1000000480	≥14 days after initially booked vaccination/ information visit date up to 8 months
Hospitalization for pericarditis	Analysis will be carried out as outlined in C3761080, EU PASS register number EUPAS1000000480	≥14 days after initially booked vaccination/ information visit date up to 8 months
Hospitalization for myocarditis	Analysis will be carried out as outlined in C3761080, EU PASS register number EUPAS1000000480	≥14 days after initially booked vaccination/ information visit date up to 8 months
Asthma exacerbation hospitalization	Analysis will be carried out as outlined in C3761080, EU PASS register number EUPAS1000000480	≥14 days after initially booked vaccination/ information visit date up to 8 months
RSV-related respiratory tract disease hospitalization by hepatic or renal impairment status	Among those with hepatic or renal impairment at baseline. Analysis will be carried out as outlined in C3761080, EU PASS register number EUPAS1000000480	≥14 days after initially booked vaccination/ information visit date up to 8 months
Hospitalization for RSV-related lower respiratory tract disease in subsequent 2025/2026 and 2026/2027 RSV seasons		From June 1, 2025 up to 12 months (2025/2026 season) and June 1, 2026 up to 12 months (2026/2027 season)
RSV-related MACE		≥14 days after initially booked vaccination/ information visit date up to 8 months
Laboratory-confirmed mycoplasma infection		≥14 days after initially booked vaccination/ information visit date up to 8 months
Laboratory-confirmed HMPV infection		≥14 days after initially booked vaccination/ information visit date up to 8 months
RSV-related tract disease hospitalization/emergency department visit		≥14 days after initially booked vaccination/ information visit date up to 8 months
Critical lower respiratory tract disease hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
Critical respiratory tract disease hospitalization		≥14 days after initially booked vaccination/ information visit date up to 8 months
RSV-related COPD exacerbation		≥14 days after initially booked vaccination/ information visit date up to 8 months
All-cause COPD exacerbation		≥14 days after initially booked vaccination/ information visit date up to 8 months
Asthma exacerbation		≥14 days after initially booked vaccination/ information visit date up to 8 months
RSV-related asthma exacerbation		≥14 days after initially booked vaccination/ information visit date up to 8 months

Collaborators and Investigators

• Sponsor: Tor Biering-Sørensen
• Collaborators: Pfizer
• 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

Publications and helpful links

General Publications

• Lassen MCH, Johansen ND, Christensen SH, Aliabadi N, Skaarup KG, Modin D, Claggett BL, Larsen CS, Larsen L, Wiese L, Dalager-Pedersen M, Lindholm MG, Jensen AMR, Dons M, Bernholm KF, Davidovski FS, Duus LS, Ottosen CI, Nielsen AB, Borchsenius JH, Espersen C, Kose G, Fussing FH, Pareek M, Kober L, Solomon SD, Jensen JUS, Martel CJ, Gessner BD, Schwarz C, Gonzalez E, Skovdal M, Moulton LH, Zhang P, Begier E, Biering-Sorensen T. Bivalent RSV Prefusion F Protein-Based Vaccine for Preventing Cardiovascular Hospitalizations in Older Adults: A Prespecified Analysis of the DAN-RSV Trial. JAMA. 2025 Oct 28;334(16):1431-1441. doi: 10.1001/jama.2025.15405.
• Lassen MCH, Christensen SH, Johansen ND, Aliabadi N, Skaarup KG, Modin D, Claggett BL, Larsen CS, Larsen L, Wiese L, Dalager-Pedersen M, Lindholm MG, Kober L, Solomon SD, Staehr Jensen JU, Martel CJ, Schwarz C, Gonzalez E, Skovdal M, Moulton LH, Zhang P, Gessner BD, Begier E, Biering-Sorensen T. A pragmatic individually randomized trial to evaluate bivalent RSV prefusion F protein-based vaccine effectiveness for preventing RSV hospitalizations in adults aged 60 years or above (DAN-RSV): Rationale and trial design. Am Heart J. 2026 Jan;291:14-25. doi: 10.1016/j.ahj.2025.07.068. Epub 2025 Jul 28.
• Lassen MCH, Johansen ND, Christensen SH, Aliabadi N, Skaarup KG, Modin D, Claggett BL, Larsen CS, Larsen L, Wiese L, Dalager-Pedersen M, Lindholm MG, Jensen AMR, Dons M, Bernholm KF, Davidovski FS, Duus LS, Ottosen CI, Nielsen AB, Borchsenius JH, Espersen C, Kose G, Fussing FH, Kober L, Solomon SD, Jensen JUS, Martel CJ, Gessner BD, Schwarz C, Gonzalez E, Skovdal M, Moulton LH, Zhang P, Begier E, Biering-Sorensen T. RSV Prefusion F Vaccine for Prevention of Hospitalization in Older Adults. N Engl J Med. 2026 Jan 8;394(2):138-151. doi: 10.1056/NEJMoa2509810. Epub 2025 Aug 30.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: November 8, 2024
• First Submitted That Met QC Criteria: November 9, 2024
• First Posted (Actual): November 12, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: RSV; Cardiovascular; Vaccination; Registry; Respiratory; Respiratory tract disease; Pragmatic; Lower respiratory tract disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: DAN-RSV; 2024-516600-42-00 (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
• product manufactured in and exported from the U.S.: No