Heart Failure Clinical Trial

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

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.

View Full Description

Full 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.

View Eligibility Criteria

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.

Study is for people with:

Heart Failure

Phase:

Phase 4

Estimated Enrollment:

5388

Study ID:

NCT02787044

Recruitment Status:

Completed

Sponsor:

Brigham and Women's Hospital

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There are 178 Locations for this study

See Locations Near You

Birmingham VAMC
Birmingham Alabama, 35233, United States
University of Alabama Hypertension Program
Birmingham Alabama, 35294, United States
Heart Center Research, LLC
Huntsville Alabama, 35801, United States
Alaska Heart & Vascular Institute
Anchorage Alaska, 99508, United States
Banner University Medicine North
Tucson Arizona, 85719, United States
University of Arizona- Sarver Heart Center
Tucson Arizona, 85724, United States
CAVHS
Little Rock Arkansas, 72205, United States
VA Loma Linda Healthcare System
Loma Linda California, 92357, United States
Long Beach VAMC
Long Beach California, 90822, United States
University of California Davis Medical Center
Sacramento California, 95817, United States
VA San Diego Healthcare System
San Diego California, 92161, United States
UCSF Medical Center
San Francisco California, 94143, United States
VA West Haven
West Haven Connecticut, 06516, United States
Washington DC VAMC
Washington District of Columbia, 20422, United States
Clearwater Cardiovascular Consultants
Clearwater Florida, 33756, United States
N FL/S GA Veterans Health System
Gainesville Florida, 32608, United States
OneFlorida CDRN
Gainesville Florida, 32611, United States
Clearwater Cardiovascular Consultants-Largo
Largo Florida, 33777, United States
Inpatient Research Corporation
Miami Florida, 33014, United States
ITB Research
Miami Florida, 33173, United States
Charlotte Heart Group Research Center
Port Charlotte Florida, 33952, United States
Clearwater Cardiovascular Consultants-SH
Safety Harbor Florida, 34695, United States
Bond Community Health Center, Inc.
Tallahassee Florida, 32301, United States
Piedmont Heart Institute
Atlanta Georgia, 30309, United States
Morehouse School of Medicine
Atlanta Georgia, 30310, United States
Atlanta VA Health Care System
Decatur Georgia, 30033, United States
Peidmont Fayette
Fayetteville Georgia, 30214, United States
University of Hawaii
Honolulu Hawaii, 96813, United States
Northwestern University
Chicago Illinois, 60611, United States
Jesse Brown VA Medical Center
Chicago Illinois, 60612, United States
University of Chicago Medicine
Chicago Illinois, 60637, United States
Chicago Medical Research
Hazel Crest Illinois, 60429, United States
Northwester Medicine Lake Forest
Lake Forest Illinois, 60045, United States
Loyola University Medical Center
Maywood Illinois, 60153, United States
Captain James A. Lovell Federal Health Care Center
North Chicago Illinois, 60064, United States
UnityPoint Health Methodist
Peoria Illinois, 61606, United States
Central DuPage Hospital
Winfield Illinois, 60190, United States
Krannert Institute of Cardiology
Indianapolis Indiana, 46202, United States
St. Vincent Medical Group
Indianapolis Indiana, 46260, United States
University of Iowa
Iowa City Iowa, 52242, United States
The University of Kansas Medical Center
Kansas City Kansas, 66160, United States
VA Eastern Kansas Health Care System
Leavenworth Kansas, 66048, United States
Robley Rex VA
Louisville Kentucky, 40206, United States
The Heart Clinic of Hamond
Hammond Louisiana, 70403, United States
Southeast Louisiana Veterans Healthcare System
New Orleans Louisiana, 70112, United States
Ochsner Health System- Baton Rouge
New Orleans Louisiana, 70121, United States
ENRM VA Hospital
Bedford Massachusetts, 01730, United States
Brigham and Women's Hospital
Boston Massachusetts, 02115, United States
Brigham and Women's Faulkner Hospital
Boston Massachusetts, 02130, United States
Beth Israel Deaconess Medical Center
Boston Massachusetts, 02215, United States
Pentucket Medical Associates
Haverhill Massachusetts, 01830, United States
Charles River Medical Associates
Natick Massachusetts, 01760, United States
Boston/West Roxbury VA Hospital
West Roxbury Massachusetts, 02132, United States
VA Boston Healthcase System
West Roxbury Massachusetts, 02132, United States
VA Ann Harbor Healthcare System
Ann Arbor Michigan, 48105, United States
Abbott Northwestern Hospital
Minneapolis Minnesota, 55407, United States
HealthPartners - Riverside Research
Minneapolis Minnesota, 55454, United States
University of Minnesota
Minneapolis Minnesota, 55455, United States
Mayo Clinic
Rochester Minnesota, 55905, United States
HealthEast Medical Research Institute
Saint Paul Minnesota, 55102, United States
University of Mississippi Medical Center
Jackson Mississippi, 39216, United States
Kansas City VA Medical Center
Kansas City Missouri, 64128, United States
VA St. Louis Health Care System
Saint Louis Missouri, 63106, United States
St. Louis University
Saint Louis Missouri, 63110, United States
Washington University School of Medicine
Saint Louis Missouri, 63110, United States
Nebraska Heart Institute- Grand Island
Grand Island Nebraska, 68803, United States
Darthmouth-Hitchcock Medical Center
Lebanon New Hampshire, 03756, United States
Cardio Assoc. of the Del. Valley- Elmer
Elmer New Jersey, 08318, United States
Cardio. Assoc. of the Del. Valley- Haddon Heights
Haddon Heights New Jersey, 08035, United States
Cardio. Assoc. of the Del. Valley- Sewell
Sewell New Jersey, 08080, United States
Lourdes Cardiology Services
Voorhees New Jersey, 08043, United States
New Mexico VA Health Care System
Albuquerque New Mexico, 87108, United States
Albany Medical College
Albany New York, 12208, United States
New York Presbyterian Brooklyn Methodist Hospital
Brooklyn New York, 11215, United States
New York Presbyterian Queens Bayside/Whitestone
Flushing New York, 11355, United States
New York Presbyterian/Queens
Flushing New York, 11355, United States
NYPQ - Cardiology Outpatient Clinic
Flushing New York, 11355, United States
Winthrop University Hospital
Mineola New York, 11501, United States
New York VA
New York New York, 10010, United States
NYU Langone Medical Center
New York New York, 10016, United States
New York Presbyterian
New York New York, 10021, United States
Columbia University Medical Center
New York New York, 10032, United States
University of Rochester Medical Center
Rochester New York, 14642, United States
Stony Brook University Hospital
Stony Brook New York, 11794, United States
Charles George VA
Asheville North Carolina, 28805, United States
University of North Carolina at Chapel Hill
Chapel Hill North Carolina, 27599, United States
Duke
Durham North Carolina, 27710, United States
Louis Stokes Cleveland VA Medical Center
Cleveland Ohio, 44106, United States
Cleveland Clinic
Cleveland Ohio, 44195, United States
Ohio State University
Columbus Ohio, 43210, United States
Heart House Research Foundation
Springfield Ohio, 45504, United States
Oregon Health & Science
Portland Oregon, 97239, United States
VA Portland Health Care Systems (VAPHCS)
Portland Oregon, 97239, United States
Temple University
Philadelphia Pennsylvania, 19140, United States
University of Pittsburgh
Pittsburgh Pennsylvania, 15213, United States
Providence VA Medical Center
Providence Rhode Island, 02908, United States
Medical University of South Carolina
Charleston South Carolina, 29425, United States
WJB Dorn VAMC
Columbia South Carolina, 29209, United States
Palmetto Research Center, LLC
Spartanburg South Carolina, 29302, United States
VAMC Memphis
Memphis Tennessee, 38104, United States
Meharry Medical College
Nashville Tennessee, 37208, United States
Tennessee Valley Healthcare Systems-Nashville
Nashville Tennessee, 37212, United States
Vanderbilt University
Nashville Tennessee, 37232, United States
Austin Heart- Heart Hospital
Austin Texas, 78756, United States
Baylor Scott and White Heart and Vascular Hospital
Dallas Texas, 75226, United States
Michael E. DeBakey VAMC, Houston
Houston Texas, 77030, United States
Houston Heart & Vascular Associates
Kingwood Texas, 77339, United States
Houston Methodist Research Institute-CCAT Pearland
Pearland Texas, 77584, United States
St. David's Heath & Vascular PLLC
Round Rock Texas, 78681, United States
South Texas Veterans Healthcare System
San Antonio Texas, 78229, United States
STAR Clinical Trials
San Antonio Texas, 78229, United States
Austin Heart San Marcos
San Marcos Texas, 78666, United States
Baylor Scott and White Research Institute
Temple Texas, 76508, United States
University of Utah
Salt Lake City Utah, 84108, United States
George E. Wahlen Dept of VA Affairs Medical Center
Salt Lake City Utah, 84148, United States
VA Medical Center White River Junction
White River Junction Vermont, 05009, United States
Inova Heart and Vascular Institute
Alexandria Virginia, 22306, United States
Carient Heart & Vascular
Manassas Virginia, 20109, United States
Louis A Johnson VAMC
Clarksburg West Virginia, 26301, United States
Gundersen Clinic
La Crosse Wisconsin, 54601, United States
University of Wisconsin
Madison Wisconsin, 53705, United States
Willam S. Middleton Memorial Veterans Hospital
Madison Wisconsin, 53705, United States
University of Wisconsin Madison
Madison Wisconsin, 57305, United States
Marshfield Clinic
Marshfield Wisconsin, 54449, United States
Medical College of Wisconsin
Milwaukee Wisconsin, 53226, United States
Aurora Research Institute, LLC
Milwaukee Wisconsin, 53233, United States
Celement J. Zablocki VA Medical Center
Milwaukee Wisconsin, 53295, United States
TotalCardiology
Calgary Alberta, T2E 7, Canada
University of Calgary
Calgary Alberta, T2N4Z, Canada
CK Hui Heart Centre, Royal Alexandra Hospital
Edmonton Alberta, T5H3V, Canada
Dr. MPJ Senaratne Professional Corporation
Edmonton Alberta, T6K4C, Canada
Northwest Echocardiolography
Grande Prairie Alberta, T8V 2, Canada
The CARe Clinic (Central Alberta Research)
Red Deer Alberta, T4N6V, Canada
University of Alberta Hospital- Mazankoski Heart Institute
Edmonton British Columbia, T6G2B, Canada
Kelowna General Hospital
Kelowna British Columbia, V1Y1T, Canada
SMH Cardiology Clinical
Surrey British Columbia, V3V 0, Canada
Manna Research Inc. (Vancouver)
Vancouver British Columbia, V5X0C, Canada
Vancouver General Hospital - Gordon Leslie Diamond Centre
Vancouver British Columbia, V5Z1M, Canada
St. Paul's Hospital
Vancouver British Columbia, V6Z1Y, Canada
Victoria Heart Institute Foundation
Victoria British Columbia, V8R4R, Canada
St. Boniface Hospital/University of Manitoba
Winnipeg Manitoba, R2H2A, Canada
University of Sherbrooke
Dieppe New Brunswick, , Canada
G.A Research Associates Ltd.
Moncton New Brunswick, E1G 1, Canada
QEII Health Sciences
Halifax Nova Scotia, B3H2Y, Canada
Brampton Research Assocaites
Brampton Ontario, L6Z 4, Canada
Manna Research Inc. (Burlington North)
Burlington Ontario, L7M 4, Canada
Manna Research Inc. (Burlington South)
Burlington Ontario, L7R 1, Canada
Cambridge Cardiac Care Center
Cambridge Ontario, N1R 6, Canada
Vizel Cardiac Research
Cambridge Ontario, N1R 7, Canada
Dr. Alan David Bell
Downsview Ontario, M3M 3, Canada
Hamilton Health Sciences General Hospital/ McMaste
Hamilton Ontario, L8L 2, Canada
Queen's University CardioPulmonary Unit
Kingston Ontario, K7L 3, Canada
St. Joseph's Health Care
London Ontario, N6A 4, Canada
Dixie Medical Group
Mississauga Ontario, L4W 0, Canada
Apple Hills Medical Associates
Mississauga Ontario, L4Y 2, Canada
PACE
Newmarket Ontario, L3Y 2, Canada
North York General Hospital
North York Ontario, M2K 1, Canada
Sewa Ram Singal Med Prof Corporation
North York Ontario, M3N 1, Canada
Heart Care Research
Oshawa Ontario, L1J 2, Canada
Dr. James Cha
Oshawa Ontario, L1J 2, Canada
Montfort Hospital and Ottawa Cardiovascular Centre
Ottawa Ontario, K1K 0, Canada
University of Ottawa Heart Institute
Ottawa Ontario, K1Y 4, Canada
Heart Function Clinic Queensway Carleton
Ottawa Ontario, K2H 8, Canada
Kawartha Cardiology
Peterborough Ontario, K9J0B, Canada
Scarborough General Hospital
Scarborough Ontario, M1P 2, Canada
St. Catherines Hospital
St. Catherines Ontario, L2M 5, Canada
Manna Research (Stoney Creek)
Stoney Creek Ontario, L8J 3, Canada
Health Sciences North Research Institute
Sudbury Ontario, P3E 5, Canada
Dr. D. Shukla Professional Medicine Corporation
Sudbury Ontario, P3E 5, Canada
Dr. R. Labonte Professional Medicine Corporation
Sudbury Ontario, P3E 5, Canada
Thunder Bay Regional Health Sciences Center
Thunder Bay Ontario, P7B 6, Canada
Sunnybrook Health Sciences Centre
Toronto Ontario, M4N 3, Canada
St. Michael's Hospital
Toronto Ontario, M5B 1, Canada
Mount Sinai Hospital
Toronto Ontario, M5G 1, Canada
Toronto General Hospital
Toronto Ontario, M5G 2, Canada
Women's College Hospital
Toronto Ontario, M5S 1, Canada
University of Toronto
Toronto Ontario, , Canada
iHealthCentre
Vaughan Ontario, L4H 0, Canada
CISSS de Laval, Hopital Cite de la Sante
Laval Quebec, H7M 3, Canada
Montreal Heart Institute
Montréal Quebec, H1T 1, Canada
McGill University Health Centre
Montréal Quebec, H3G 1, Canada
Jewish General Hospital
Montréal Quebec, H3T 1, Canada
CIUSSS NÃŽM Hopital du Sacre-Coeur de Montreal
Montréal Quebec, H4J 1, Canada
Manna Research Inc. (Montreal)
Montréal Quebec, H9R 4, Canada
IUCPQ
Quebec City Quebec, G1V 4, Canada
Centre hospitalier régional de Lanaudière
St-Charles Borromee Quebec, J6E 6, Canada
CISSSI- Hopital Pierre-Le Gardeur
Terrebonne Quebec, J6V 2, Canada
Centre Hospitalier de Regional Trois-Rivieres
Trois-Rivières Quebec, G8Z 3, Canada
Prairie Vascular Research Inc.
Regina Saskatchewan, 54P 0, Canada
VA Caribbean Healthcare System
San Juan , 00921, Puerto Rico

How clear is this clinincal trial information?

Study is for people with:

Heart Failure

Phase:

Phase 4

Estimated Enrollment:

5388

Study ID:

NCT02787044

Recruitment Status:

Completed

Sponsor:


Brigham and Women's Hospital

How clear is this clinincal trial information?

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