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

IF 3.5 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

American heart journal Pub Date : 2025-07-28 DOI:10.1016/j.ahj.2025.07.068

Mats C. Højbjerg Lassen MD , Sine H. Christensen MSc , Niklas D. Johansen MD , Negar Aliabadi MD, MS , Kristoffer G. Skaarup MD , Daniel Modin MD , Brian L. Claggett PhD , Carsten S. Larsen MD, DMSc , Lykke Larsen MD, PhD , Lothar Wiese MD, PhD , Michael Dalager-Pedersen MD, PhD , Matias G. Lindholm MD, PhD , Lars Køber MD, DMSc , Scott D. Solomon MD , Jens Ulrik Stæhr Jensen MD, PhD , Cyril Jean-Marie Martel PhD , Claudia Schwarz PhD , Elisa Gonzalez MS , Mette Skovdal MSc , Lawrence H. Moulton PhD, MS , Tor Biering-Sørensen MD, MSc, MPH, PhD

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引用次数: 0

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 (https://clinicaltrials.gov/study/NCT06684743)

查看原文本刊更多论文

一项评估基于二价RSV预融合F蛋白疫苗预防60岁及以上成人RSV住院（DAN-RSV）有效性的实用个体随机试验：理论基础和试验设计

背景：呼吸道合胞病毒（RSV）可在老年人和慢性病患者中引起严重疾病。虽然二价RSVpreF疫苗已被证明可预防rsv相关呼吸道疾病，但其对严重rsv相关和更广泛的心肺疾病住院治疗的影响仍未在一项完全随机试验中得到检验。这项实用的、单独随机、开放标签、平行组试验旨在评估RSVpreF疫苗在降低60岁及以上成人rsv相关和全因心肺疾病住院风险方面的有效性（VE）。方法：DAN-RSV将丹麦成年人1:1随机分组，接种RSV疫苗或不接种RSV疫苗。该试验使用全国注册系统进行招募，通过国家电子信息系统识别和邀请符合条件的公民，并可以远程提供电子知情同意。基线、安全性和结果数据是通过国家卫生登记处收集的，使用同意时提供的民事登记号码。在2024/2025冬季期间，将有多达13万名参与者参加。主要目的是评估VE对rsv相关呼吸道疾病住院治疗的影响。次要终点包括rsv相关和全因下呼吸道疾病住院、rsv相关和全因心肺疾病住院以及全因死亡。结论：DAN-RSV是一项创新试验，结合了个体随机化的黄金标准和通过集中健康记录和国家健康登记收集的实用数据。该设计提供了一种可行的方法来评估RSVpreF对60岁以上成人临床有意义的心肺结局的影响，同时通过使用随机化最小化偏倚。研究结果将支持成本效益分析，并为未来的疫苗接种政策提供信息。试验注册：NCT06684743，于2024年11月9日注册（https://clinicaltrials.gov/study/NCT06684743）。

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来源期刊

American heart journal 医学-心血管系统

CiteScore

8.20

自引率

2.10%

发文量

214

审稿时长

38 days

期刊介绍： The American Heart Journal will consider for publication suitable articles on topics pertaining to the broad discipline of cardiovascular disease. Our goal is to provide the reader primary investigation, scholarly review, and opinion concerning the practice of cardiovascular medicine. We especially encourage submission of 3 types of reports that are not frequently seen in cardiovascular journals: negative clinical studies, reports on study designs, and studies involving the organization of medical care. The Journal does not accept individual case reports or original articles involving bench laboratory or animal research.