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Phase 4 Completed N=5,260 Randomized Quadruple-blind Prevention

INfluenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure

Source: ClinicalTrials.gov NCT02787044 ↗
Enrolled (actual)
5,260
Serious AEs
0.1%
Results posted
Sep 2021
Primary outcomePrimary: All-Cause Death or Cardiopulmonary Hospitalization Within Each Vaccination Season — 975; 924 Participant-Seasons — p=0.21
◆ Published Evidence
Highly cited
129citations · ~26 / year
Effect of High-Dose Trivalent vs Standard-Dose Quadrivalent Influenza Vaccine on Mortality or Cardiopulmonary Hospitalization in Patients With High-risk Cardiovascular Disease: A Randomized Clinical Trial.
JAMA · 2021 · Open access · High-confidence link

Summary

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.

Linked Publications (5)

  • Effect of High-Dose Trivalent vs Standard-Dose Quadrivalent Influenza Vaccine on Mortality or Cardiopulmonary Hospitalization in Patients With High-risk Cardiovascular Disease: A Randomized Clinical Trial.
    JAMA · 2021 · 129 citations · Open access · High-confidence link
  • Influenza Vaccine Immune Response in Patients With High-Risk Cardiovascular Disease: A Secondary Analysis of the INVESTED Randomized Clinical Trial.
    JAMA cardiology · 2024 · 14 citations · Open access · Likely link
  • Stratified proportional win-fractions regression analysis.
    Statistics in medicine · 2022 · 10 citations · Open access · Likely link
  • Temporal Association Among Influenza-Like Illness, Cardiovascular Events, and Vaccine Dose in Patients With High-Risk Cardiovascular Disease: Secondary Analysis of a Randomized Clinical Trial.
    JAMA network open · 2023 · 7 citations · Open access · Likely link
  • Educational Attainment Level and Risk of Mortality and Cardiopulmonary Outcomes in High-Risk Patients With Cardiovascular Disease: The INVESTED Trial.
    Journal of the American Heart Association · 2025 · 1 citation · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
All-Cause Death or Cardiopulmonary Hospitalization Within Each Vaccination Season
975; 924 0.21
SECONDARY
Total Cardiopulmonary Hospitalizations or Death
1857; 1784 0.44
SECONDARY
Cardiovascular Death or Hospitalization Within Each Vaccination Season
805; 752 0.16
SECONDARY
Death or Cardiopulmonary Hospitalization Across Enrolling Seasons
955; 918 0.26
SECONDARY
All-Cause Mortality
223; 222 0.96

Eligibility Criteria

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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02787044) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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