High-dose influenza vaccine to reduce clinical outcomes in high-risk cardiovascular patients: Rationale and design of the INVESTED trial

Orly Vardeny, Jacob A. Udell, Jacob Joseph, Michael E. Farkouh, Adrian F. Hernandez, Alison J. McGeer, H. Keipp Talbot, Deepak L. Bhatt, Christopher P. Cannon, Shaun G. Goodman, Inder Anand, David L. DeMets, Jon Temte, Janet Wittes, Kristin Nichol, Clyde W. Yancy, J. Michael Gaziano, Lawton S. Cooper, Kyung Mann Kim, Scott D. Solomon

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Background: Influenza leads to significant cardiopulmonary morbidity and mortality—particularly in patients with cardiovascular disease—that may be prevented with a standard influenza vaccine. However, patients with cardiovascular conditions have a reduced immune response to influenza vaccine, potentially resulting in reduced effectiveness for preventing clinical events. High-dose vaccine augments immune response in cardiac patients, suggesting that a high-dose influenza vaccination strategy may further reduce morbidity and mortality. Alternatively, broader coverage with an influenza vaccine containing an increased number of viral strains is an alternative strategy without direct evaluation. Research design and methods: INfluenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated heart failure (INVESTED) is a pragmatic, randomized, double-blind, parallel-group, active-controlled trial comparing the effectiveness of an annual vaccination strategy of high-dose trivalent versus standard-dose quadrivalent influenza vaccine in patients with a history of recent heart failure or myocardial infarction hospitalization. The trial will enroll approximately 9,300 patients over 4 influenza seasons. The primary hypothesis is that high-dose influenza vaccine will reduce the composite outcome of all-cause mortality and hospitalization from a cardiovascular or pulmonary cause compared with standard-dose influenza vaccine within each enrolling season. Approximately 1,300 primary outcome events will provide >90% power to detect an 18% relative risk reduction at a 2-sided α level of.05. Conclusion: INVESTED is the largest and longest study to assess whether high-dose influenza vaccine is superior to standard-dose influenza vaccine in reducing cardiopulmonary events in a high-risk cardiovascular population (ClinicalTrials.gov Identifier: NCT02787044).

Original languageEnglish (US)
Pages (from-to)97-103
Number of pages7
JournalAmerican Heart Journal
Volume202
DOIs
StatePublished - Aug 2018

Bibliographical note

Funding Information:
INVESTED is funded by the NHLBI ( U01 HL130163 and U01 HL130204 ). Additional funds for site payments and vaccine are provided by Sanofi Pasteur , which has no scientific role in the INVESTED trial. Additional funds for the biological specimen acquisition are provided by grants from Heart and Stroke Foundation of Canada ( ERLI024 ) and the Mount Sinai Hospital/University Health Network AMO Innovation Fund ( 21502002 ).

Funding Information:
INVESTED is funded by the NHLBI (U01 HL130163 and U01 HL130204). Additional funds for site payments and vaccine are provided by Sanofi Pasteur, which has no scientific role in the INVESTED trial. Additional funds for the biological specimen acquisition are provided by grants from Heart and Stroke Foundation of Canada (ERLI024) and the Mount Sinai Hospital/University Health Network AMO Innovation Fund (21502002).

Publisher Copyright:
© 2018

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