Influenza infection is associated with an increased risk of subsequent CV events. High-dose influenza vaccines are approved for use in older adults, but are not routinely used in this setting despite evidence indicating additional protection against both influenza infection and influenza-related morbidity compared with standard-dose vaccines.1,2
Until recently, no randomised trial has compared the relative efficacy of high-dose quadrivalent influenza vaccines (QIV-HD) with standard-dose QIV (QIV-SD) on CV and respiratory events and mortality in a broad elderly population. The DANFLU-1 trial investigated the feasibility of conducting a large-scale, pragmatic, individually randomised trial to assess the effectiveness of QIV-HD and QIV-SD in older individuals.
This open-label study integrated a pragmatic randomised trial into the existing official Danish vaccination programme. Adults aged 65 to 79 years were randomised 1:1 to receive either QIV-HD or QIV-SD. Following vaccination, participant data were transferred to a central trial site and linked to nationwide Danish administrative health registries, from which all other data were obtained.
Senior author and chief investigator, Professor Tor Biering-Sørensen (University of Copenhagen - Copenhagen, Denmark) explains: “The trial only required one study visit with almost all information obtained from administrative health registries. This greatly reduced the burden on both participants and investigators.”
The primary objective was to evaluate the feasibility of the design and to compare baseline characteristics between the arms and the overall Danish population (65 to 79 years). The secondary objective was to estimate the relative vaccine effectiveness of the two doses on a range of CV and respiratory endpoints.
Among the 12,477 participants analysed, the average age was 71.7 years (47.1% were women). Registry-based data collection was feasible and there was complete follow-up information for 99.97% of participants. Baseline characteristics of the trial participants and the Danish population were similar.
The use of QIV-HD was associated with fewer hospitalisations for influenza and pneumonia than QIV-SD (0.2% versus 0.4%) and had a relative vaccine effectiveness of 64.4% (95% CI 24.4 to 84.6). QIV-HD also led to a lower incidence of all-cause mortality than QIV-SD (0.3% versus 0.7%), with a relative vaccine effectiveness of 48.9% (95% CI 11.5 to 71.3).
Prof. Biering-Sørensen comments: “Conducting an innovative pragmatic randomised trial in Denmark using administrative health registries as the primary data source was feasible. Integrating an influenza vaccine trial into the official Danish vaccination programme was also feasible.” In terms of the relative vaccine effectiveness, he observes: “The reductions in hospitalisations and all-cause mortality with the high-dose vaccine were encouraging but require confirmation in a larger trial before potentially guiding clinical practice.” He concludes: “The next step is to conduct a fully powered trial of high-dose versus standard-dose QIV in older adults. The required sample size is expected to be around 200,000 participants.”
The results were presented by Doctor Niklas Dyrby Johansen (Herlev and Gentofte Hospital - Copenhagen, Denmark) at a Hot Line session yesterday.