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A Pragmatic Randomized Trial to Evaluate the Vaccine Effectiveness of Bivalent RSV prefusion F Vaccine for Preventing RSV Hospitalizations in Adults (DAN-RSV): Trial Design Update

Mats C Højbjerg Lassen, Sine H Christensen, Niklas D Johansen, Marat Yafasov, Manan Pareek, Abby E Rudolph, Carmen Rodriguez-Tenreiro-Sánchez, Kristoffer G Skaarup, Daniel Modin, Brian L Claggett, Carsten S Larsen, Lykke Larsen, Lothar Wiese, Michael Dalager-Pedersen, Matias G Lindholm, Lars Køber, Scott D Solomon, Jens Ulrik Stæhr Jensen, Cyril Jean-Marie Martel, Negar AliabadiClaudia Schwarz, Mette Skovdal, Pingping Zhang, Vanessa López-Gómez, Sabrina Welsh, Bradford D Gessner, Federico Martinón-Torres, Elizabeth Begier, Tor Biering-Sørensen*

*Corresponding author af dette arbejde

Abstract

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity in adults, particularly among older individuals and those with comorbidities. The DAN-RSV trial was initiated to evaluate bivalent RSV prefusion F (RSVpreF) vaccine effectiveness in preventing RSV-related hospitalizations.

METHODS: DAN-RSV is a large-scale, pragmatic, randomized clinical trial that enrolled participants during the 2024/2025 (Danish adults aged ≥60 years) and 2025/2026 (adults aged ≥18 years in Denmark and Galicia, Spain) Northern hemisphere winter seasons. In Denmark, nationwide registries and the national electronic messaging system were used to identify and recruit eligible citizens; individuals could provide electronic informed consent remotely or in-person. In Galicia, participants were recruited via text message invitations and consented on-site.

RESULTS: During the initial 2024/2025 season, 131,379 Danish adults aged ≥60 years were enrolled. Following lower-than-expected event accrual and expansion of the EU indication to adults 18 years and older, the trial was extended to continue enrollment of adults aged ≥18 years across Denmark and Galicia, Spain during the 2025/2026 RSV season. Key protocol updates include expansion of the eligibility criteria to adults aged ≥18 years, inclusion of an additional study site within the integrated public healthcare infrastructure of Galicia, Spain, and an increase in the planned sample size to up to approximately 690,000 participants across both seasons. The randomization strategy (1:1 to RSVpreF vaccine or no vaccine), primary endpoint (RSV-related respiratory tract disease hospitalization), and statistical framework, including intention-to-treat analyses and hierarchical testing, remain unchanged.

CONCLUSION: The extension of the DAN-RSV trial is expected to improve statistical precision, enhance generalizability, and strengthen the robustness of the effect estimates. The updated design will provide reliable randomized evidence on bivalent RSVpreF vaccine effectiveness to inform clinical and public health decision-making.

OriginalsprogEngelsk
Artikelnummer107497
TidsskriftAmerican Heart Journal
Vol/bind300
ISSN0002-8703
DOI
StatusE-pub ahead of print - 30 maj 2026

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