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 - 07/10/25

Doi : 10.1016/j.ahj.2025.07.068

Mats C. Højbjerg Lassen, MD ^a,^b, Sine H. Christensen, MSc ^a,^b, Niklas D. Johansen, MD ^a,^b, Negar Aliabadi, MD, MS ^c, Kristoffer G. Skaarup, MD ^a,^b, Daniel Modin, MD ^a,^b, Brian L. Claggett, PhD ^d, Carsten S. Larsen, MD, DMSc ^e, Lykke Larsen, MD, PhD ^f, Lothar Wiese, MD, PhD ^g, Michael Dalager-Pedersen, MD, PhD ^h,ⁱ, Matias G. Lindholm, MD, PhD ^j, Lars Køber, MD, DMSc ^k,^l, Scott D. Solomon, MD ^d, Jens Ulrik Stæhr Jensen, MD, PhD ^k,^m, Cyril Jean-Marie Martel, PhD ⁿ, Claudia Schwarz, PhD ^c, Elisa Gonzalez, MS ^c, Mette Skovdal, MSc ^c, Lawrence H. Moulton, PhD, MS ^o, Pingping Zhang, MS ^c, Bradford D. Gessner, MD ^c, Elizabeth Begier, MD, MPH ^c, Tor Biering-Sørensen, MD, MSc, MPH, PhD ^a,^b,^k,^p,^⁎
^a Department of Cardiology, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark
^b Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
^c Pfizer Inc., New York, NY
^d Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
^e Department of Clinical Medicine – Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
^f Research Unit for Infectious Diseases, Odense University Hospital, Odense, Denmark
^g Department of Infectious Diseases, Zealand University Hospital, Roskilde, Denmark
^h Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
ⁱ Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark
^j Department of Cardiology, Zealand University Hospital Roskilde, Roskilde, Denmark
^k Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
^l Department of Cardiology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
^m Respiratory Medicine Section, Department of Medicine, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark
ⁿ Epidemiological Infectious Disease Preparedness, Statens Serum Institut, Copenhagen, Denmark
^o Pfizer Canada, Kirkland, Quebec, Canada
^p Steno Diabetes Center Copenhagen, Copenhagen, Denmark

^⁎Reprint requests: Tor Biering-Sørensen, MD, MSc, MPH, PhD, Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital – Herlev and Gentofte, Gentofte Hospitalsvej 8, 3.th., 2900, Hellerup, Denmark.Center for Translational Cardiology and Pragmatic Randomized TrialsDepartment of CardiologyCopenhagen University Hospital – Herlev and GentofteGentofte Hospitalsvej 8, 3.th.Hellerup2900Denmark

ABSTRACT

Background

Respiratory syncytial virus (RSV) can cause serious illness in older adults and those with chronic conditions. While the bivalent RSVpreF vaccine has been shown to protect against RSV-related respiratory tract disease, its impact on severe RSV-related and broader cardiorespiratory hospitalizations remains untested in a fully powered randomized trial. This pragmatic, individually randomized, open-label, parallel-group trial aims to evaluate RSVpreF vaccine effectiveness (VE) in reducing the risk of RSV-related and all-cause cardiorespiratory hospitalizations in adults aged 60 and older.

Methods

DAN-RSV is randomizing Danish adults 1:1 to receive either RSVpreF or no RSV vaccine. The trial uses nationwide registries for recruitment, where eligible citizens are identified and invited via the national electronic messaging system and can provide electronic informed consent remotely. Baseline, safety, and outcome data are collected through the national health registries using the civil registration number provided at consent. Up to 130,000 participants will be enrolled during the 2024/2025 winter season. The primary objective is to assess vaccine effectiveness (VE) against RSV-related respiratory tract disease hospitalization. Secondary endpoints include RSV-related and all-cause lower respiratory tract disease hospitalizations, RSV-related and all-cause cardiorespiratory hospitalizations, and all-cause death.

Conclusion

DAN-RSV is an innovative trial combining the gold standard of individual randomization with pragmatic data collection via centralized health records and national health registries. This design offers a feasible approach to assess the impact of RSVpreF on clinically meaningful cardio-respiratory outcomes in adults ≥60 years in a real-world setting – while minimizing bias through use of randomization. The results will support cost-effectiveness analyses and inform future vaccination policies.

Trial registration

NCT06684743, registered November 9, 2024 (NCT06684743)

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Plan

Background

Purpose

Methods

Study design and organization

Trial population and recruitment

Randomization and blinding

Intervention and comparator

Data collection and data sources

Endpoints

Safety monitoring

Power and sample size

Statistical analysis

Additional prespecified analyses

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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 - 07/10/25

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Trial registration

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