Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated heart failure (INVESTED) I s a multi-center, randomized, double blind, active-control trial of high dose influenza vaccine compared to standard dose influenza vaccine for three seasons in adult participants with a history of myocardial infarction or heart failure. The primary outcome measure is the composite of death or cardiopulmonary hospitalizations, and secondary outcomes include composite of cardiopulmonary death or cardiopulmonary hospitalization, all-cause death or all-cause hospitalization, all-cause death or cardiovascular hospitalization, cardiopulmonary death, and all cause death. Background: The substantial number of individuals in North America with myocardial infarction or heart failure (HF) are at high risk for influenza infection and associated morbidity, mortality and increased health care costs despite annual influenza vaccination. Higher dose of vaccine is approved for use in older adults but not in patients with heart failure. Antibody-mediated immunity contributes to vaccine-induced protection from influenza illness. Preliminary data: Our research group has shown in a meta-analysis that influenza vaccine reduces the risk for cardiovascular events and has also demonstrated reduced antibody titers to influenza vaccination in patients with HF. Additionally, we've shown in a pilot study that double dose influenza vaccine resulted in increased titers and was well tolerated. Methods: A multi-center, randomized, double blinded randomized trial will be conducted with 4650 patients assigned to the standard dose vaccine dose and 4650 patients to high dose influenza vaccine. The primary outcome measure is the composite of death or cardiopulmonary hospitalization, assessed at the end of each influenza season. Secondary outcomes will include the composite of death or cardiovascular hospitalizations, death or all-cause hospitalizations, and mortality. The study will also examine associations between geometric mean antibody titers and risk for death or cardiopulmonary hospitalizations. Significance: A positive trial may be able to provide crucial information to infom health care policy regarding optimal influenza vaccination dosing among individuals with high risk cardiovascular disease.

Public Health Relevance

Influenza infection is known to be associated with increased risk of cardiovascular events, and leads to significant morbidity and mortality each year. Annual influenza vaccination is recommended by the Centers for Disease Control and Prevention, but the optimal vaccine regimen that portends the most protection in patients with high risk cardiovascular disease is unclear. The INVESTED study is a multi-center, randomized, active- control clinical trial of high dose influenza vaccine compared to standard dose influenza vaccine for three seasons in adult individuals with a history of myocardial infarction or heart failure who are at high risk for cardiovascular events. The primary outcome is time to first occurrence of death or cardiopulmonary hospitalization, and key secondary outcomes include time to occurrence of the cardiopulmonary death or cardiopulmonary hospitalizations, time to occurrence of all-cause death or all-cause hospitalizations, time to occurrence of all-cause death or cardiovascular hospitalizations, cardiopulmonary death, and all-cause death. The association between geometric mean antibody titers with the risk for death or cardiopulmonary hospitalizations will also be investigated. The results of this trial have the potential to inform health care policy regarding optimal influenza vaccination for individuals with high risk cardiovascular disease, which may in turn reduce morbidity from this annual threat to health stability in patients with cardiovascular conditions. (End of Abstract)

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL130163-03
Application #
9417055
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Cooper, Lawton S
Project Start
2016-02-15
Project End
2021-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115