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INfluenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure
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StatusAccepting Candidates
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Age18 Years - N/A
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SexesAll
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Healthy VolunteersNo
Objective
INVESTED will test the hypothesis that high dose trivalent influenza vaccine will reduce cardiopulmonary events to a greater extent than standard dose quadrivalent influenza vaccine in high-risk cardiovascular patients with a recent history of myocardial infarction or heart failure. The trial will enroll 9300 participants over one Vanguard (pilot) season and three additional influenza seasons. The primary endpoint will be a composite of all-cause mortality or cardiopulmonary hospitalization.
Description
Influenza leads to significant morbidity and mortality, particularly in patients with cardiovascular disease. Influenza-related death is more common in patients with cardiovascular disease than any other chronic health condition. Influenza infection has been temporally associated with acute cardiovascular events, such as acute coronary syndrome and acute heart failure. Due to the increased risk for influenza-related complications, annual influenza immunization is recommended by the Centers for Disease Control and Prevention, (CDC) the American Heart Association, and the American College of Cardiology, and widespread influenza vaccination has been associated with reduced cardiac-related hospital admissions, acute exacerbations of heart failure, and winter mortality. Moreover, a meta-analysis has shown that annual vaccination reduces the risk for major adverse cardiovascular events (MACE) by 36%, with a more prominent effect in those with recent acute myocardial infarction (AMI).
Several lines of evidence suggest that a strategy of utilizing high-dose influenza vaccine in at risk cardiovascular patients would reduce morbidity and mortality. Immune responses to influenza vaccine, normally subject to variability by age and concomitant medical conditions, are substantially reduced in patients with heart failure evidenced by lower vaccine-induced antibody titers compared to healthy controls. In a randomized trial, antibody responses in patients with heart failure were augmented by using a higher dose of influenza vaccine. In a meta-analysis, higher dose influenza vaccination was associated with a 27% reduced risk for MACE compared to standard dose vaccine. A randomized study of high dose versus standard dose influenza vaccine in medically-stable patients over age 65 showed that participants receiving high dose vaccine had a 24% reduced risk of laboratory-confirmed influenza associated with protocol-defined influenza-like-illness, and had a low risk for adverse events. High dose influenza vaccine is FDA approved for use in medically stable adults over the age of 65, but has not been studied for patients under the age of 65 or in those with unstable, high risk medical conditions. The CDC does not preferentially recommend one influenza vaccine over another, and the optimal vaccine formulation that offers the most clinical protection in these high risk patients is unknown.
The high morbidity and health care costs among patients with high risk cardiovascular disease along with the reduced immune responses to standard dose influenza vaccines in patients with heart failure provides a compelling rationale to investigate alternative influenza vaccination strategies in this group. INVESTED is an outcomes study in patients with recent acute myocardial infarction (AMI) or heart failure (HF) to test whether a four-fold higher dose of trivalent influenza vaccine will reduce morbidity and mortality compared to standard dose quadrivalent vaccine. INVESTED will test the hypothesize that high dose vaccine will reduce the composite of all cause death or cardiopulmonary hospitalizations in this population, with the following specific aims:
Specific Aim 1. To test the hypothesis that high dose trivalent influenza vaccine will reduce the composite of death or cardiopulmonary events compared with standard dose quadrivalent influenza vaccine in high-risk cardiovascular patients. Patients with recent AMI or HF hospitalization will be randomized to high dose versus standard dose vaccine for up to three influenza seasons. The primary endpoint will be time to first occurrence of death or cardiopulmonary hospitalization within each influenza season. Hospitalizations will be ascertained utilizing multiple approaches (phone, patient report, and electronic health records). Key secondary outcome measures will include total (first and recurrent) cardiopulmonary hospitalizations or death, time to first occurrence of cardiovascular death or cardiopulmonary hospitalization, time to occurrence of all-cause death or cardiopulmonary hospitalization across all enrolled influenza seasons, time to occurrence of all-cause death, and time to first occurrence of cardiopulmonary hospitalizations.
Specific Aim 2. To test the hypothesis that antibody titers to influenza vaccine antigens are associated with cardiopulmonary outcomes. In a subset of participants, antibody titers by hemagglutination inhibition assays to influenza vaccine antigens at baseline and at 4 weeks following randomization will be determined, corresponding to achievement of maximal antibody titer levels after vaccination. The association between geometric mean titers post-vaccination and the occurrence of death or cardiopulmonary hospitalization (primary outcome measure of Specific Aim 1) will be assessed.
Other key correlative study (immune) outcome measures will include:
Change in antibody titers at 4 weeks post-vaccination from baseline to influenza vaccine antigens Seroconversion (demonstration of 4-fold rise in antibody concentrations from baseline) and seroprotection (demonstration of antibody titer level of 1:40) to A/H1N1, A/H3N2, and B-type vaccine antigens
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.
Details
Full study title | INfluenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated heart failure (INVESTED) |
Protocol number | OCR17713 |
ClinicalTrials.gov ID | NCT02787044 |
Phase | Phase 4 |
Eligibility
Inclusion Criteria:
>= 18 years of age
history of hospitalization for myocardial infarction within 1 year of enrollment OR a history of hospitalization for heart failure within 2 years of enrollment
At least one of the following additional risk factors:
Prior MI (if HF the index event above; or a second MI)
Prior HF hospitalization (if MI the index event above; or a second HF event)
Age ≥ 65
Left ventricular ejection fraction (LVEF) < 40%
Diabetes mellitus
Obesity (BMI ≥ 30)
Renal impairment (eGFR ≤ 60)
History of ischemic stroke
History of peripheral artery disease
Current smoking
Exclusion Criteria:
Known allergy, hypersensitivity (anaphylaxis), or Guillain-Barré Syndrome within 6 weeks after influenza vaccine
Any non-cardiac condition that in the opinion of the investigator would lead to life expectancy less than 9 months.
Receipt of influenza vaccine during current influenza season
Any illness requiring treatment with antibiotics or anti-inflammatory medication within the past 14 days.
Any fever over 100 degrees Fahrenheit or 38 degrees Celsius within the past 7 days.
Lead researcher
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Carl J Pepine, MDCardiologist (Heart Specialist)
Participate in a study
Here are some general steps to consider when participating in a research study:
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Step1
Contact the research team
Call or email the research team listed within the specific clinical trial or study to let them know that you're interested. A member of the research team, such as the researcher or study coordinator, will be available to tell you more about the study and to answer any questions or concerns you may have.
Primary contact
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Step2
Get screened to confirm eligibility
You may be asked to take part in prescreening to make sure you are eligible for a study. The prescreening process ensures it is safe for you to participate. During the prescreening process, you will be asked some questions and you may also be asked to schedule tests or procedures to confirm your eligibility.
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Step3
Provide your consent to participate
If you are eligible and want to join the clinical trial or study, a member of the research team will ask for your consent to participate. To give consent, you will be asked to read and sign a consent form for the study. This consent form explains the study's purpose, procedures, risks, benefits and provides other important information, such as the study team's contact information.
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Step4
Participate
If you decide to participate in a clinical trial or study, the research team will keep you informed of the study requirements and what you will need to do to throughout the study. For some trials or studies, your health care provider may work with the research team to ensure there are no conflicts with other medications or treatments.