NCT02787044

Brief 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5,388

participants targeted

Target at P75+ for phase_4 heart-failure

Timeline
Completed

Started Aug 2016

Typical duration for phase_4 heart-failure

Geographic Reach
3 countries

190 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 25, 2016

Completed
7 days until next milestone

First Posted

Study publicly available on registry

June 1, 2016

Completed
2 months until next milestone

Study Start

First participant enrolled

August 1, 2016

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 31, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 31, 2020

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

September 14, 2021

Completed
Last Updated

January 21, 2022

Status Verified

December 1, 2021

Enrollment Period

3.8 years

First QC Date

May 25, 2016

Results QC Date

May 24, 2021

Last Update Submit

December 22, 2021

Conditions

Keywords

influenza vaccinecardiopulmonary hospitalizationheart failuremyocardial infarctionclinical trial

Outcome Measures

Primary Outcomes (1)

  • All-Cause Death or Cardiopulmonary Hospitalization Within Each Vaccination Season

    Number of patients with first occurrence of death or cardiopulmonary hospitalization within each vaccination season

    Up to 1 year from vaccination (repeats seasonally)

Secondary Outcomes (4)

  • Total Cardiopulmonary Hospitalizations or Death

    Up to 3 years

  • Cardiovascular Death or Hospitalization Within Each Vaccination Season

    Up to one year from vaccination

  • Death or Cardiopulmonary Hospitalization Across Enrolling Seasons

    Up to three years

  • All-Cause Mortality

    Up to 3 years

Study Arms (2)

High Dose Influenza Vaccine

EXPERIMENTAL

High Dose Influenza Vaccine

Biological: High Dose Trivalent Influenza Vaccine

Standard Dose Influenza Vaccine

ACTIVE COMPARATOR

Standard Dose Influenza Vaccine

Biological: Standard Dose Quadrivalent Influenza Vaccine

Interventions

High Dose Trivalent Influenza Vaccine

High Dose Influenza Vaccine

Standard Dose Quadrivalent Influenza Vaccine

Standard Dose Influenza Vaccine

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \>= 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (190)

Birmingham VAMC

Birmingham, Alabama, 35233, United States

Location

University of Alabama Hypertension Program

Birmingham, Alabama, 35294, United States

Location

Heart Center Research, LLC

Huntsville, Alabama, 35801, United States

Location

Alaska Heart & Vascular Institute

Anchorage, Alaska, 99508, United States

Location

Banner University Medicine North

Tucson, Arizona, 85719, United States

Location

University of Arizona- Sarver Heart Center

Tucson, Arizona, 85724, United States

Location

CAVHS

Little Rock, Arkansas, 72205, United States

Location

VA Loma Linda Healthcare System

Loma Linda, California, 92357, United States

Location

Long Beach VAMC

Long Beach, California, 90822, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

VA San Diego Healthcare System

San Diego, California, 92161, United States

Location

UCSF Medical Center

San Francisco, California, 94143, United States

Location

VA West Haven

West Haven, Connecticut, 06516, United States

Location

Washington DC VAMC

Washington D.C., District of Columbia, 20422, United States

Location

Clearwater Cardiovascular Consultants

Clearwater, Florida, 33756, United States

Location

N FL/S GA Veterans Health System

Gainesville, Florida, 32608, United States

Location

OneFlorida CDRN

Gainesville, Florida, 32611, United States

Location

Clearwater Cardiovascular Consultants-Largo

Largo, Florida, 33777, United States

Location

Inpatient Research Corporation

Miami, Florida, 33014, United States

Location

ITB Research

Miami, Florida, 33173, United States

Location

Charlotte Heart Group Research Center

Port Charlotte, Florida, 33952, United States

Location

Clearwater Cardiovascular Consultants-SH

Safety Harbor, Florida, 34695, United States

Location

Bond Community Health Center, Inc.

Tallahassee, Florida, 32301, United States

Location

Piedmont Heart Institute

Atlanta, Georgia, 30309, United States

Location

Morehouse School of Medicine

Atlanta, Georgia, 30310, United States

Location

Atlanta VA Health Care System

Decatur, Georgia, 30033, United States

Location

Peidmont Fayette

Fayetteville, Georgia, 30214, United States

Location

University of Hawaii

Honolulu, Hawaii, 96813, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Jesse Brown VA Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Chicago Medical Research

Hazel Crest, Illinois, 60429, United States

Location

Northwester Medicine Lake Forest

Lake Forest, Illinois, 60045, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Captain James A. Lovell Federal Health Care Center

North Chicago, Illinois, 60064, United States

Location

UnityPoint Health Methodist

Peoria, Illinois, 61606, United States

Location

Central DuPage Hospital

Winfield, Illinois, 60190, United States

Location

Krannert Institute of Cardiology

Indianapolis, Indiana, 46202, United States

Location

St. Vincent Medical Group

Indianapolis, Indiana, 46260, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

The University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

VA Eastern Kansas Health Care System

Leavenworth, Kansas, 66048, United States

Location

Robley Rex VA

Louisville, Kentucky, 40206, United States

Location

The Heart Clinic of Hamond

Hammond, Louisiana, 70403, United States

Location

Southeast Louisiana Veterans Healthcare System

New Orleans, Louisiana, 70112, United States

Location

Ochsner Health System- Baton Rouge

New Orleans, Louisiana, 70121, United States

Location

ENRM VA Hospital

Bedford, Massachusetts, 01730, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Faulkner Hospital

Boston, Massachusetts, 02130, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Pentucket Medical Associates

Haverhill, Massachusetts, 01830, United States

Location

Charles River Medical Associates

Natick, Massachusetts, 01760, United States

Location

Boston/West Roxbury VA Hospital

West Roxbury, Massachusetts, 02132, United States

Location

VA Boston Healthcase System

West Roxbury, Massachusetts, 02132, United States

Location

VA Ann Harbor Healthcare System

Ann Arbor, Michigan, 48105, United States

Location

Abbott Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

HealthPartners - Riverside Research

Minneapolis, Minnesota, 55454, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

HealthEast Medical Research Institute

Saint Paul, Minnesota, 55102, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Kansas City VA Medical Center

Kansas City, Missouri, 64128, United States

Location

VA St. Louis Health Care System

St Louis, Missouri, 63106, United States

Location

St. Louis University

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nebraska Heart Institute- Grand Island

Grand Island, Nebraska, 68803, United States

Location

Darthmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Cardio Assoc. of the Del. Valley- Elmer

Elmer, New Jersey, 08318, United States

Location

Cardio. Assoc. of the Del. Valley- Haddon Heights

Haddon Heights, New Jersey, 08035, United States

Location

Cardio. Assoc. of the Del. Valley- Sewell

Sewell, New Jersey, 08080, United States

Location

Lourdes Cardiology Services

Voorhees Township, New Jersey, 08043, United States

Location

New Mexico VA Health Care System

Albuquerque, New Mexico, 87108, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

New York Presbyterian Brooklyn Methodist Hospital

Brooklyn, New York, 11215, United States

Location

New York Presbyterian Queens Bayside/Whitestone

Flushing, New York, 11355, United States

Location

New York Presbyterian/Queens

Flushing, New York, 11355, United States

Location

NYPQ - Cardiology Outpatient Clinic

Flushing, New York, 11355, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

New York VA

New York, New York, 10010, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

New York Presbyterian

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

Charles George VA

Asheville, North Carolina, 28805, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke

Durham, North Carolina, 27710, United States

Location

Louis Stokes Cleveland VA Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Heart House Research Foundation

Springfield, Ohio, 45504, United States

Location

Oregon Health & Science

Portland, Oregon, 97239, United States

Location

VA Portland Health Care Systems (VAPHCS)

Portland, Oregon, 97239, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Providence VA Medical Center

Providence, Rhode Island, 02908, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

WJB Dorn VAMC

Columbia, South Carolina, 29209, United States

Location

Palmetto Research Center, LLC

Spartanburg, South Carolina, 29302, United States

Location

VAMC Memphis

Memphis, Tennessee, 38104, United States

Location

Meharry Medical College

Nashville, Tennessee, 37208, United States

Location

Tennessee Valley Healthcare Systems-Nashville

Nashville, Tennessee, 37212, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Austin Heart- Heart Hospital

Austin, Texas, 78756, United States

Location

Baylor Scott and White Heart and Vascular Hospital

Dallas, Texas, 75226, United States

Location

Michael E. DeBakey VAMC, Houston

Houston, Texas, 77030, United States

Location

Houston Heart & Vascular Associates

Kingwood, Texas, 77339, United States

Location

Houston Methodist Research Institute-CCAT Pearland

Pearland, Texas, 77584, United States

Location

St. David's Heath & Vascular PLLC

Round Rock, Texas, 78681, United States

Location

South Texas Veterans Healthcare System

San Antonio, Texas, 78229, United States

Location

STAR Clinical Trials

San Antonio, Texas, 78229, United States

Location

Austin Heart San Marcos

San Marcos, Texas, 78666, United States

Location

Baylor Scott and White Research Institute

Temple, Texas, 76508, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

George E. Wahlen Dept of VA Affairs Medical Center

Salt Lake City, Utah, 84148, United States

Location

VA Medical Center White River Junction

White River Junction, Vermont, 05009, United States

Location

Inova Heart and Vascular Institute

Alexandria, Virginia, 22306, United States

Location

Carient Heart & Vascular

Manassas, Virginia, 20109, United States

Location

Louis A Johnson VAMC

Clarksburg, West Virginia, 26301, United States

Location

Gundersen Clinic

La Crosse, Wisconsin, 54601, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Willam S. Middleton Memorial Veterans Hospital

Madison, Wisconsin, 53705, United States

Location

University of Wisconsin Madison

Madison, Wisconsin, 57305, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Aurora Research Institute, LLC

Milwaukee, Wisconsin, 53233, United States

Location

Celement J. Zablocki VA Medical Center

Milwaukee, Wisconsin, 53295, United States

Location

TotalCardiology

Calgary, Alberta, T2E 7C5, Canada

Location

University of Calgary

Calgary, Alberta, T2N4Z6, Canada

Location

CK Hui Heart Centre, Royal Alexandra Hospital

Edmonton, Alberta, T5H3V9, Canada

Location

Dr. MPJ Senaratne Professional Corporation

Edmonton, Alberta, T6K4C1, Canada

Location

Northwest Echocardiolography

Grande Prairie, Alberta, T8V 2E7, Canada

Location

The CARe Clinic (Central Alberta Research)

Red Deer, Alberta, T4N6V7, Canada

Location

University of Alberta Hospital- Mazankoski Heart Institute

Edmonton, British Columbia, T6G2B7, Canada

Location

Kelowna General Hospital

Kelowna, British Columbia, V1Y1T2, Canada

Location

SMH Cardiology Clinical

Surrey, British Columbia, V3V 0C6, Canada

Location

Manna Research Inc. (Vancouver)

Vancouver, British Columbia, V5X0C4, Canada

Location

Vancouver General Hospital - Gordon Leslie Diamond Centre

Vancouver, British Columbia, V5Z1M9, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, V6Z1Y6, Canada

Location

Victoria Heart Institute Foundation

Victoria, British Columbia, V8R4R2, Canada

Location

St. Boniface Hospital/University of Manitoba

Winnipeg, Manitoba, R2H2A6, Canada

Location

University of Sherbrooke

Dieppe, New Brunswick, Canada

Location

G.A Research Associates Ltd.

Moncton, New Brunswick, E1G 1A7, Canada

Location

QEII Health Sciences

Halifax, Nova Scotia, B3H2Y9, Canada

Location

Brampton Research Assocaites

Brampton, Ontario, L6Z 4N5, Canada

Location

Manna Research Inc. (Burlington North)

Burlington, Ontario, L7M 4Y1, Canada

Location

Manna Research Inc. (Burlington South)

Burlington, Ontario, L7R 1A4, Canada

Location

Cambridge Cardiac Care Center

Cambridge, Ontario, N1R 6V6, Canada

Location

Vizel Cardiac Research

Cambridge, Ontario, N1R 7R1, Canada

Location

Dr. Alan David Bell

Downsview, Ontario, M3M 3E5, Canada

Location

Health Sciences North Research Institute

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Dr. D. Shukla Professional Medicine Corporation

Greater Sudbury, Ontario, P3E 5M4, Canada

Location

Dr. R. Labonte Professional Medicine Corporation

Greater Sudbury, Ontario, P3E 5M4, Canada

Location

Hamilton Health Sciences General Hospital/ McMaste

Hamilton, Ontario, L8L 2X2, Canada

Location

Queen's University CardioPulmonary Unit

Kingston, Ontario, K7L 3N6, Canada

Location

St. Joseph's Health Care

London, Ontario, N6A 4V2, Canada

Location

Dixie Medical Group

Mississauga, Ontario, L4W 0C2, Canada

Location

Apple Hills Medical Associates

Mississauga, Ontario, L4Y 2N8, Canada

Location

PACE

Newmarket, Ontario, L3Y 2P6, Canada

Location

North York General Hospital

North York, Ontario, M2K 1E1, Canada

Location

Sewa Ram Singal Med Prof Corporation

North York, Ontario, M3N 1N1, Canada

Location

Heart Care Research

Oshawa, Ontario, L1J 2J9, Canada

Location

Dr. James Cha

Oshawa, Ontario, L1J 2K1, Canada

Location

Montfort Hospital and Ottawa Cardiovascular Centre

Ottawa, Ontario, K1K 0T2, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Heart Function Clinic Queensway Carleton

Ottawa, Ontario, K2H 8P4, Canada

Location

Kawartha Cardiology

Peterborough, Ontario, K9J0B2, Canada

Location

St. Catherines Hospital

Saint Catherines, Ontario, L2M 5V4, Canada

Location

Scarborough General Hospital

Scarborough Village, Ontario, M1P 2T7, Canada

Location

Manna Research (Stoney Creek)

Stoney Creek, Ontario, L8J 3W2, Canada

Location

Thunder Bay Regional Health Sciences Center

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

Women's College Hospital

Toronto, Ontario, M5S 1B2, Canada

Location

University of Toronto

Toronto, Ontario, Canada

Location

iHealthCentre

Vaughan, Ontario, L4H 0P6, Canada

Location

CISSS de Laval, Hopital Cite de la Sante

Laval, Quebec, H7M 3L9, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

McGill University Health Centre

Montreal, Quebec, H3G 1A4, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

CIUSSS NÎM Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, H4J 1C5, Canada

Location

Manna Research Inc. (Montreal)

Montreal, Quebec, H9R 4S3, Canada

Location

IUCPQ

Québec, Quebec, G1V 4G5, Canada

Location

Centre hospitalier régional de Lanaudière

Saint-Charles-Borromée, Quebec, J6E 6J2, Canada

Location

CISSSI- Hopital Pierre-Le Gardeur

Terrebonne, Quebec, J6V 2H2, Canada

Location

Centre Hospitalier de Regional Trois-Rivieres

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Prairie Vascular Research Inc.

Regina, Saskatchewan, 54P 0W5, Canada

Location

VA Caribbean Healthcare System

San Juan, 00921, Puerto Rico

Location

Related Publications (14)

  • Vardeny O, Sweitzer NK, Detry MA, Moran JM, Johnson MR, Hayney MS. Decreased immune responses to influenza vaccination in patients with heart failure. J Card Fail. 2009 May;15(4):368-73. doi: 10.1016/j.cardfail.2008.11.009. Epub 2008 Dec 18.

    PMID: 19398087BACKGROUND
  • Vardeny O, Moran JJ, Sweitzer NK, Johnson MR, Hayney MS. Decreased T-cell responses to influenza vaccination in patients with heart failure. Pharmacotherapy. 2010 Jan;30(1):10-6. doi: 10.1592/phco.30.1.10.

    PMID: 20030468BACKGROUND
  • Van Ermen A, Hermanson MP, Moran JM, Sweitzer NK, Johnson MR, Vardeny O. Double dose vs. standard dose influenza vaccination in patients with heart failure: a pilot study. Eur J Heart Fail. 2013 May;15(5):560-4. doi: 10.1093/eurjhf/hfs207. Epub 2013 Jan 4.

    PMID: 23291729BACKGROUND
  • Albrecht CM, Sweitzer NK, Johnson MR, Vardeny O. Lack of persistence of influenza vaccine antibody titers in patients with heart failure. J Card Fail. 2014 Feb;20(2):105-9. doi: 10.1016/j.cardfail.2013.12.008. Epub 2013 Dec 19.

    PMID: 24361852BACKGROUND
  • Udell JA, Farkouh ME, Solomon SD, Vardeny O. Does influenza vaccination influence cardiovascular complications? Expert Rev Cardiovasc Ther. 2015 Jun;13(6):593-6. doi: 10.1586/14779072.2015.1044439. Epub 2015 May 14.

    PMID: 25971953BACKGROUND
  • Vardeny O, Claggett B, Udell JA, Packer M, Zile M, Rouleau J, Swedberg K, Desai AS, Lefkowitz M, Shi V, McMurray JJV, Solomon SD; PARADIGM-HF Investigators. Influenza Vaccination in Patients With Chronic Heart Failure: The PARADIGM-HF Trial. JACC Heart Fail. 2016 Feb;4(2):152-158. doi: 10.1016/j.jchf.2015.10.012. Epub 2015 Dec 30.

    PMID: 26746371BACKGROUND
  • Udell JA, Zawi R, Bhatt DL, Keshtkar-Jahromi M, Gaughran F, Phrommintikul A, Ciszewski A, Vakili H, Hoffman EB, Farkouh ME, Cannon CP. Association between influenza vaccination and cardiovascular outcomes in high-risk patients: a meta-analysis. JAMA. 2013 Oct 23;310(16):1711-20. doi: 10.1001/jama.2013.279206.

    PMID: 24150467BACKGROUND
  • Vardeny O, Udell JA, Joseph J, Farkouh ME, Hernandez AF, McGeer AJ, Talbot HK, Bhatt DL, Cannon CP, Goodman SG, Anand I, DeMets DL, Temte J, Wittes J, Nichol K, Yancy CW, Gaziano JM, Cooper LS, Kim K, Solomon SD. High-dose influenza vaccine to reduce clinical outcomes in high-risk cardiovascular patients: Rationale and design of the INVESTED trial. Am Heart J. 2018 Aug;202:97-103. doi: 10.1016/j.ahj.2018.05.007. Epub 2018 May 23.

    PMID: 29909156BACKGROUND
  • Vardeny O, Kim K, Udell JA, Joseph J, Desai AS, Farkouh ME, Hegde SM, Hernandez AF, McGeer A, Talbot HK, Anand I, Bhatt DL, Cannon CP, DeMets D, Gaziano JM, Goodman SG, Nichol K, Tattersall MC, Temte JL, Wittes J, Yancy C, Claggett B, Chen Y, Mao L, Havighurst TC, Cooper LS, Solomon SD; INVESTED Committees and Investigators. 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 Jan 5;325(1):39-49. doi: 10.1001/jama.2020.23649.

  • Lassen MCH, Howell N, Claggett BL, Biering-Sorensen T, Vardeny O, Solomon SD, Udell J, Joseph J, Hegde SM. Educational Attainment Level and Risk of Mortality and Cardiopulmonary Outcomes in High-Risk Patients With Cardiovascular Disease: The INVESTED Trial. J Am Heart Assoc. 2025 Jul;14(13):e040221. doi: 10.1161/JAHA.124.040221. Epub 2025 Jun 18.

  • Peikert A, Claggett BL, Udell JA, Joseph J, Hegde SM, Kim K, Mao L, Wang T, Havighurst TC, Farkouh ME, Bhatt DL, Tattersall MC, Cooper LS, Solomon SD, Vardeny O. Influenza Vaccine Immune Response in Patients With High-Risk Cardiovascular Disease: A Secondary Analysis of the INVESTED Randomized Clinical Trial. JAMA Cardiol. 2024 Jun 1;9(6):574-581. doi: 10.1001/jamacardio.2024.0468.

  • Hegde SM, Claggett BL, Udell JA, Kim K, Joseph J, Farkouh ME, Peikert A, Bhatt AS, Tattersall MC, Bhatt DL, Cooper LS, Solomon SD, Vardeny O. 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 Netw Open. 2023 Sep 5;6(9):e2331284. doi: 10.1001/jamanetworkopen.2023.31284.

  • Wang T, Mao L. Stratified proportional win-fractions regression analysis. Stat Med. 2022 Nov 20;41(26):5305-5318. doi: 10.1002/sim.9570. Epub 2022 Sep 14.

  • Vardeny O, Hernandez AF, Cohen LW, Franklin A, Baqai M, Palmer S, Bierer BE, Cobb N. Transitioning to the National Institutes of Health single institutional review board model: Piloting the use of the Streamlined, Multi-site, Accelerated Resources for Trials IRB Reliance. Clin Trials. 2019 Jun;16(3):290-296. doi: 10.1177/1740774519832911. Epub 2019 Mar 13.

Related Links

MeSH Terms

Conditions

Heart FailureMyocardial InfarctionInfluenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesMyocardial IschemiaVascular DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosisRespiratory Tract InfectionsInfectionsOrthomyxoviridae InfectionsRNA Virus InfectionsVirus DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral VaccinesVaccinesBiological ProductsComplex Mixtures

Results Point of Contact

Title
Dr. Scott Solomon
Organization
Brigham and Women's Hospital

Study Officials

  • Orly Vardeny, PharmD, MS

    University of Minnesota

    PRINCIPAL INVESTIGATOR
  • Scott D Solomon, MD

    Brigham and Women's Hospital

    PRINCIPAL INVESTIGATOR
  • KyungMann Kim, PhD

    University of Wisconsin, Madison

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

May 25, 2016

First Posted

June 1, 2016

Study Start

August 1, 2016

Primary Completion

May 31, 2020

Study Completion

May 31, 2020

Last Updated

January 21, 2022

Results First Posted

September 14, 2021

Record last verified: 2021-12

Data Sharing

IPD Sharing
Will share

Data will be shared according to NIH data sharing rules

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR
Time Frame
Data will be available as per NIH guidelines on December 4, 2022 (2 years from the primary study publication date).
Access Criteria
Data will be available to all qualified researchers based on the NIH BIOLINCC criteria.
More information

Locations