Rosalind Hollingsworth1, Arto Palmu2, Stephanie Pepin3, Martin Dupuy4, Anju Shrestha5, Jukka Jokinen6, Ritva Syrjänen2, Joshua Nealon7, Sandrine Samson1, Iris De Bruijn8. 1. Global Medical Affairs, Sanofi Pasteur, Swiftwater, PA. 2. Finnish Institute for Health and Welfare, Tampere, Finland. 3. Global Clinical Sciences, Sanofi Pasteur, Marcy L'Etoile, France. Electronic address: stephanie.pepin@sanofipasteur.com. 4. Biostatistics Sciences, Sanofi Pasteur, Marcy L'Etoile, France. 5. Global Pharmacovigilance, Sanofi Pasteur, Swiftwater, PA. 6. Finnish Institute for Health and Welfare, Helsinki, Finland. 7. Vaccines Epidemiology and Modelling, Sanofi Pasteur, Lyon, France. 8. Global Clinical Sciences, Sanofi Pasteur, Marcy L'Etoile, France.
Abstract
BACKGROUND: Influenza has been an acknowledged cause of respiratory disease for decades. However, considerable related, and often unappreciated, disease burden stems from cardiovascular complications, exacerbations of underlying medical conditions and secondary respiratory complications, with the highest burden in the elderly. This novel study combines the gold standard method of a randomized controlled trial with real-world data collection through national registries, to assess the relative effectiveness of high-dose (QIV-HD) vs standard-dose quadrivalent influenza vaccine (QIV-SD) in preventing cardio-respiratory hospitalizations in a large cohort of adults aged ≥65 years. METHODS AND RESULTS: This trial (NCT04137887) is a Phase III/IV, modified double-blinded, randomized, registry-based trial, conducted by the Finnish Institute for Health and Welfare (THL). Participants (n>120 000) are being enrolled over multiple influenza seasons and randomized (1:1) to receiveQIV-HD or QIV-SD. Participant follow-up is based on data collection up to 11 months post-vaccination using Finnish national health registries. The primary objective is to demonstrate the relative superior effectiveness of QIV-HD over QIV-SD in preventing cardio-respiratory hospitalizations up to 6 months post-vaccination. Safety will be assessed using automated online tools throughout the study, with causality assessed using statistical and probabilistic methods; serious adverse reactions and adverse events of special interest will be investigated individually. CONCLUSION: This large, real-world, randomized study will provide valuable insight into the contribution of influenza in causing severe cardio-respiratory events, and the role of vaccination with QIV-HD in reducing these outcomes compared to the current standard of care. FUNDING: Sanofi Pasteur.
RCT Entities:
BACKGROUND: Influenza has been an acknowledged cause of respiratory disease for decades. However, considerable related, and often unappreciated, disease burden stems from cardiovascular complications, exacerbations of underlying medical conditions and secondary respiratory complications, with the highest burden in the elderly. This novel study combines the gold standard method of a randomized controlled trial with real-world data collection through national registries, to assess the relative effectiveness of high-dose (QIV-HD) vs standard-dose quadrivalent influenza vaccine (QIV-SD) in preventing cardio-respiratory hospitalizations in a large cohort of adults aged ≥65 years. METHODS AND RESULTS: This trial (NCT04137887) is a Phase III/IV, modified double-blinded, randomized, registry-based trial, conducted by the Finnish Institute for Health and Welfare (THL). Participants (n>120 000) are being enrolled over multiple influenza seasons and randomized (1:1) to receive QIV-HD or QIV-SD. Participant follow-up is based on data collection up to 11 months post-vaccination using Finnish national health registries. The primary objective is to demonstrate the relative superior effectiveness of QIV-HD over QIV-SD in preventing cardio-respiratory hospitalizations up to 6 months post-vaccination. Safety will be assessed using automated online tools throughout the study, with causality assessed using statistical and probabilistic methods; serious adverse reactions and adverse events of special interest will be investigated individually. CONCLUSION: This large, real-world, randomized study will provide valuable insight into the contribution of influenza in causing severe cardio-respiratory events, and the role of vaccination with QIV-HD in reducing these outcomes compared to the current standard of care. FUNDING: Sanofi Pasteur.
Authors: Joshua Nealon; Daniel Modin; Rebecca E Ghosh; Deborah Rudin; Gunnar Gislason; Helen P Booth; Jens Ulrik Stæhr Jensen; Rachael Williams; Hilary Shepherd; Eleanor Yelland; Helene Bricout; Sandra S Chaves; Tor Biering-Sørensen Journal: NPJ Vaccines Date: 2022-02-23 Impact factor: 7.344
Authors: Bahar Behrouzi; Deepak L Bhatt; Christopher P Cannon; Orly Vardeny; Douglas S Lee; Scott D Solomon; Jacob A Udell Journal: JAMA Netw Open Date: 2022-04-01