AzTrials
AzTrials

Heart FailurePhase 4INVESTEDNCT02787044

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

A Phase 4 study testing High Dose Trivalent Influenza Vaccine and Standard Dose Quadrivalent Influenza Vaccine in people with Heart Failure and Myocardial Infarction, run by Brigham and Women's Hospital at 190 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Heart Failure, Myocardial Infarction
What is being tested?
High Dose Trivalent Influenza Vaccine and Standard Dose Quadrivalent Influenza Vaccine
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5,388 participants
Where
190 sitesin 3 countries
Study dates
1 Aug 2016to 31 May 2020
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • >= 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
Show all 13Show fewer
  • 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

Who cannot join

  • 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.

Trial locations and contacts

190 sites in 3 countries.

190 sites in 3 countries

United States127 sites

  • Albany Medical College

    Albany, New York, 12208

  • New Mexico VA Health Care System

    Albuquerque, New Mexico, 87108

  • Inova Heart and Vascular Institute

    Alexandria, Virginia, 22306

  • Alaska Heart & Vascular Institute

    Anchorage, Alaska, 99508

  • VA Ann Harbor Healthcare System

    Ann Arbor, Michigan, 48105

  • Charles George VA

    Asheville, North Carolina, 28805

  • Piedmont Heart Institute

    Atlanta, Georgia, 30309

  • Morehouse School of Medicine

    Atlanta, Georgia, 30310

  • Austin Heart- Heart Hospital

    Austin, Texas, 78756

  • ENRM VA Hospital

    Bedford, Massachusetts, 01730

  • Birmingham VAMC

    Birmingham, Alabama, 35233

  • University of Alabama Hypertension Program

    Birmingham, Alabama, 35294

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Brigham and Women's Faulkner Hospital

    Boston, Massachusetts, 02130

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • New York Presbyterian Brooklyn Methodist Hospital

    Brooklyn, New York, 11215

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Northwestern University

    Chicago, Illinois, 60611

  • Jesse Brown VA Medical Center

    Chicago, Illinois, 60612

  • University of Chicago Medicine

    Chicago, Illinois, 60637

  • Louis A Johnson VAMC

    Clarksburg, West Virginia, 26301

  • Clearwater Cardiovascular Consultants

    Clearwater, Florida, 33756

  • Louis Stokes Cleveland VA Medical Center

    Cleveland, Ohio, 44106

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • WJB Dorn VAMC

    Columbia, South Carolina, 29209

  • Ohio State University

    Columbus, Ohio, 43210

  • Baylor Scott and White Heart and Vascular Hospital

    Dallas, Texas, 75226

  • Atlanta VA Health Care System

    Decatur, Georgia, 30033

  • Duke

    Durham, North Carolina, 27710

  • Cardio Assoc. of the Del. Valley- Elmer

    Elmer, New Jersey, 08318

  • Peidmont Fayette

    Fayetteville, Georgia, 30214

  • New York Presbyterian Queens Bayside/Whitestone

    Flushing, New York, 11355

  • New York Presbyterian/Queens

    Flushing, New York, 11355

  • NYPQ - Cardiology Outpatient Clinic

    Flushing, New York, 11355

  • N FL/S GA Veterans Health System

    Gainesville, Florida, 32608

  • OneFlorida CDRN

    Gainesville, Florida, 32611

  • Nebraska Heart Institute- Grand Island

    Grand Island, Nebraska, 68803

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

    Haddon Heights, New Jersey, 08035

  • The Heart Clinic of Hamond

    Hammond, Louisiana, 70403

  • Pentucket Medical Associates

    Haverhill, Massachusetts, 01830

  • Chicago Medical Research

    Hazel Crest, Illinois, 60429

  • University of Hawaii

    Honolulu, Hawaii, 96813

  • Michael E. DeBakey VAMC, Houston

    Houston, Texas, 77030

  • Heart Center Research, LLC

    Huntsville, Alabama, 35801

  • Krannert Institute of Cardiology

    Indianapolis, Indiana, 46202

  • St. Vincent Medical Group

    Indianapolis, Indiana, 46260

  • University of Iowa

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • The University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Kansas City VA Medical Center

    Kansas City, Missouri, 64128

  • Houston Heart & Vascular Associates

    Kingwood, Texas, 77339

  • Gundersen Clinic

    La Crosse, Wisconsin, 54601

  • Northwester Medicine Lake Forest

    Lake Forest, Illinois, 60045

  • Clearwater Cardiovascular Consultants-Largo

    Largo, Florida, 33777

  • VA Eastern Kansas Health Care System

    Leavenworth, Kansas, 66048

  • Darthmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • CAVHS

    Little Rock, Arkansas, 72205

  • VA Loma Linda Healthcare System

    Loma Linda, California, 92357

  • Long Beach VAMC

    Long Beach, California, 90822

  • Robley Rex VA

    Louisville, Kentucky, 40206

  • University of Wisconsin

    Madison, Wisconsin, 53705

  • Willam S. Middleton Memorial Veterans Hospital

    Madison, Wisconsin, 53705

  • University of Wisconsin Madison

    Madison, Wisconsin, 57305

  • Carient Heart & Vascular

    Manassas, Virginia, 20109

  • Marshfield Clinic

    Marshfield, Wisconsin, 54449

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • VAMC Memphis

    Memphis, Tennessee, 38104

  • Inpatient Research Corporation

    Miami, Florida, 33014

  • ITB Research

    Miami, Florida, 33173

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Aurora Research Institute, LLC

    Milwaukee, Wisconsin, 53233

  • Celement J. Zablocki VA Medical Center

    Milwaukee, Wisconsin, 53295

  • Winthrop University Hospital

    Mineola, New York, 11501

  • Abbott Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • HealthPartners - Riverside Research

    Minneapolis, Minnesota, 55454

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Meharry Medical College

    Nashville, Tennessee, 37208

  • Tennessee Valley Healthcare Systems-Nashville

    Nashville, Tennessee, 37212

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Charles River Medical Associates

    Natick, Massachusetts, 01760

  • Southeast Louisiana Veterans Healthcare System

    New Orleans, Louisiana, 70112

  • Ochsner Health System- Baton Rouge

    New Orleans, Louisiana, 70121

  • New York VA

    New York, New York, 10010

  • NYU Langone Medical Center

    New York, New York, 10016

  • New York Presbyterian

    New York, New York, 10021

  • Columbia University Medical Center

    New York, New York, 10032

  • Captain James A. Lovell Federal Health Care Center

    North Chicago, Illinois, 60064

  • Houston Methodist Research Institute-CCAT Pearland

    Pearland, Texas, 77584

  • UnityPoint Health Methodist

    Peoria, Illinois, 61606

  • Temple University

    Philadelphia, Pennsylvania, 19140

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Charlotte Heart Group Research Center

    Port Charlotte, Florida, 33952

  • Oregon Health & Science

    Portland, Oregon, 97239

  • VA Portland Health Care Systems (VAPHCS)

    Portland, Oregon, 97239

  • Providence VA Medical Center

    Providence, Rhode Island, 02908

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • St. David's Heath & Vascular PLLC

    Round Rock, Texas, 78681

  • University of California Davis Medical Center

    Sacramento, California, 95817

  • Clearwater Cardiovascular Consultants-SH

    Safety Harbor, Florida, 34695

  • HealthEast Medical Research Institute

    Saint Paul, Minnesota, 55102

  • University of Utah

    Salt Lake City, Utah, 84108

  • George E. Wahlen Dept of VA Affairs Medical Center

    Salt Lake City, Utah, 84148

  • South Texas Veterans Healthcare System

    San Antonio, Texas, 78229

  • STAR Clinical Trials

    San Antonio, Texas, 78229

  • VA San Diego Healthcare System

    San Diego, California, 92161

  • UCSF Medical Center

    San Francisco, California, 94143

  • Austin Heart San Marcos

    San Marcos, Texas, 78666

  • Cardio. Assoc. of the Del. Valley- Sewell

    Sewell, New Jersey, 08080

  • Palmetto Research Center, LLC

    Spartanburg, South Carolina, 29302

  • Heart House Research Foundation

    Springfield, Ohio, 45504

  • VA St. Louis Health Care System

    St Louis, Missouri, 63106

  • St. Louis University

    St Louis, Missouri, 63110

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stony Brook University Hospital

    Stony Brook, New York, 11794

  • Bond Community Health Center, Inc.

    Tallahassee, Florida, 32301

  • Baylor Scott and White Research Institute

    Temple, Texas, 76508

  • Banner University Medicine North

    Tucson, Arizona, 85719

  • University of Arizona- Sarver Heart Center

    Tucson, Arizona, 85724

  • Lourdes Cardiology Services

    Voorhees Township, New Jersey, 08043

  • Washington DC VAMC

    Washington D.C., District of Columbia, 20422

  • VA West Haven

    West Haven, Connecticut, 06516

  • Boston/West Roxbury VA Hospital

    West Roxbury, Massachusetts, 02132

  • VA Boston Healthcase System

    West Roxbury, Massachusetts, 02132

  • VA Medical Center White River Junction

    White River Junction, Vermont, 05009

  • Central DuPage Hospital

    Winfield, Illinois, 60190

Other trials in United States

Canada62 sites

  • Brampton Research Assocaites

    Brampton, Ontario, L6Z 4N5

  • Manna Research Inc. (Burlington North)

    Burlington, Ontario, L7M 4Y1

  • Manna Research Inc. (Burlington South)

    Burlington, Ontario, L7R 1A4

  • TotalCardiology

    Calgary, Alberta, T2E 7C5

  • University of Calgary

    Calgary, Alberta, T2N4Z6

  • Cambridge Cardiac Care Center

    Cambridge, Ontario, N1R 6V6

  • Vizel Cardiac Research

    Cambridge, Ontario, N1R 7R1

  • University of Sherbrooke

    Dieppe, New Brunswick

  • Dr. Alan David Bell

    Downsview, Ontario, M3M 3E5

  • CK Hui Heart Centre, Royal Alexandra Hospital

    Edmonton, Alberta, T5H3V9

  • Dr. MPJ Senaratne Professional Corporation

    Edmonton, Alberta, T6K4C1

  • University of Alberta Hospital- Mazankoski Heart Institute

    Edmonton, British Columbia, T6G2B7

  • Northwest Echocardiolography

    Grande Prairie, Alberta, T8V 2E7

  • Health Sciences North Research Institute

    Greater Sudbury, Ontario, P3E 5J1

  • Dr. D. Shukla Professional Medicine Corporation

    Greater Sudbury, Ontario, P3E 5M4

  • Dr. R. Labonte Professional Medicine Corporation

    Greater Sudbury, Ontario, P3E 5M4

  • QEII Health Sciences

    Halifax, Nova Scotia, B3H2Y9

  • Hamilton Health Sciences General Hospital/ McMaste

    Hamilton, Ontario, L8L 2X2

  • Kelowna General Hospital

    Kelowna, British Columbia, V1Y1T2

  • Queen's University CardioPulmonary Unit

    Kingston, Ontario, K7L 3N6

  • CISSS de Laval, Hopital Cite de la Sante

    Laval, Quebec, H7M 3L9

  • St. Joseph's Health Care

    London, Ontario, N6A 4V2

  • Dixie Medical Group

    Mississauga, Ontario, L4W 0C2

  • Apple Hills Medical Associates

    Mississauga, Ontario, L4Y 2N8

  • G.A Research Associates Ltd.

    Moncton, New Brunswick, E1G 1A7

  • Montreal Heart Institute

    Montreal, Quebec, H1T 1C8

  • McGill University Health Centre

    Montreal, Quebec, H3G 1A4

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • CIUSSS NÎM Hopital du Sacre-Coeur de Montreal

    Montreal, Quebec, H4J 1C5

  • Manna Research Inc. (Montreal)

    Montreal, Quebec, H9R 4S3

  • PACE

    Newmarket, Ontario, L3Y 2P6

  • North York General Hospital

    North York, Ontario, M2K 1E1

  • Sewa Ram Singal Med Prof Corporation

    North York, Ontario, M3N 1N1

  • Heart Care Research

    Oshawa, Ontario, L1J 2J9

  • Dr. James Cha

    Oshawa, Ontario, L1J 2K1

  • Montfort Hospital and Ottawa Cardiovascular Centre

    Ottawa, Ontario, K1K 0T2

  • University of Ottawa Heart Institute

    Ottawa, Ontario, K1Y 4W7

  • Heart Function Clinic Queensway Carleton

    Ottawa, Ontario, K2H 8P4

  • Kawartha Cardiology

    Peterborough, Ontario, K9J0B2

  • IUCPQ

    Québec, Quebec, G1V 4G5

  • The CARe Clinic (Central Alberta Research)

    Red Deer, Alberta, T4N6V7

  • Prairie Vascular Research Inc.

    Regina, Saskatchewan, 54P 0W5

  • St. Catherines Hospital

    Saint Catherines, Ontario, L2M 5V4

  • Centre hospitalier régional de Lanaudière

    Saint-Charles-Borromée, Quebec, J6E 6J2

  • Scarborough General Hospital

    Scarborough Village, Ontario, M1P 2T7

  • Manna Research (Stoney Creek)

    Stoney Creek, Ontario, L8J 3W2

  • SMH Cardiology Clinical

    Surrey, British Columbia, V3V 0C6

  • CISSSI- Hopital Pierre-Le Gardeur

    Terrebonne, Quebec, J6V 2H2

  • Thunder Bay Regional Health Sciences Center

    Thunder Bay, Ontario, P7B 6V4

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • Mount Sinai Hospital

    Toronto, Ontario, M5G 1X5

  • Toronto General Hospital

    Toronto, Ontario, M5G 2N2

  • Women's College Hospital

    Toronto, Ontario, M5S 1B2

  • University of Toronto

    Toronto, Ontario

  • Centre Hospitalier de Regional Trois-Rivieres

    Trois-Rivières, Quebec, G8Z 3R9

  • Manna Research Inc. (Vancouver)

    Vancouver, British Columbia, V5X0C4

  • Vancouver General Hospital - Gordon Leslie Diamond Centre

    Vancouver, British Columbia, V5Z1M9

  • St. Paul's Hospital

    Vancouver, British Columbia, V6Z1Y6

  • iHealthCentre

    Vaughan, Ontario, L4H 0P6

  • Victoria Heart Institute Foundation

    Victoria, British Columbia, V8R4R2

  • St. Boniface Hospital/University of Manitoba

    Winnipeg, Manitoba, R2H2A6

Other trials in Canada

Puerto Rico1 site

  • VA Caribbean Healthcare System

    San Juan, 00921

Other trials in Puerto Rico

About this study

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.

Read the detailed 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.

Being tested
High Dose Trivalent Influenza Vaccine, Standard Dose Quadrivalent Influenza Vaccine
Keywords
influenza vaccine, cardiopulmonary hospitalization, heart failure, myocardial infarction, clinical trial
Medical subject headings
Heart Failure, Myocardial Infarction, Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • High Dose Trivalent Influenza VaccineBiological

    High Dose Trivalent Influenza Vaccine

  • Standard Dose Quadrivalent Influenza VaccineBiological

    Standard Dose Quadrivalent Influenza Vaccine

Study groups in NCT02787044
Study groupRoleWhat they receive
High Dose Influenza VaccineExperimentalHigh Dose Influenza Vaccine
Receives: Biological: High Dose Trivalent Influenza Vaccine
Standard Dose Influenza VaccineActive comparatorStandard Dose Influenza Vaccine
Receives: Biological: Standard Dose Quadrivalent Influenza Vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Up to 1 year from vaccination (repeats seasonally)

Secondary outcomes (4)

  1. Total Cardiopulmonary Hospitalizations or Death

    Total (first and recurrent) cardiopulmonary hospitalizations or death

    Measured: Up to 3 years

  2. Cardiovascular Death or Hospitalization Within Each Vaccination Season

    Number of patients with first cardiovascular death or cardiovascular hospitalization within each influenza season

    Measured: Up to one year from vaccination

  3. Death or Cardiopulmonary Hospitalization Across Enrolling Seasons

    First cardiopulmonary Hospitalization or all-cause death across enrolling seasons

    Measured: Up to three years

  4. All-Cause Mortality

    Number of patients with first occurrence of all-cause mortality

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jun 2016 (estimated)
  2. Study start1 Aug 2016
  3. Primary completion31 May 2020
  4. Study completion31 May 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
5,388 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02787044
Sponsor's protocol ID
2015P001823
Other IDs
U01HL130163
Acronym
INVESTED
Status last verified
Dec 2021
First submitted
25 May 2016
Last updated
21 Jan 2022
Data monitoring committee
Yes
Individual data sharing
Yes: Data will be shared according to NIH data sharing rules

Publications

  • 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.

    PubMed 19398087

  • 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.

    PubMed 20030468

  • 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.

    PubMed 23291729

  • 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.

    PubMed 24361852

  • 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.

    PubMed 25971953

  • 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.

    PubMed 26746371

  • 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.

    PubMed 24150467

  • 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.

    PubMed 29909156

  • 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.

    PubMed 33275134

  • 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.

    PubMed 40530474

  • 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.

    PubMed 38583091

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Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing High Dose Trivalent Influenza Vaccine and Standard Dose Quadrivalent Influenza Vaccine in people with Heart Failure and Myocardial Infarction, run by Brigham and Women's Hospital at 190 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 190 sites in United States, Canada, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

All-Cause Death or Cardiopulmonary Hospitalization Within Each Vaccination Season (time frame: Up to 1 year from vaccination (repeats seasonally)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02787044, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2022.

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