High-Dose Influenza Vaccine in Nursing Homes

Study Description

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Brief Summary:

The purpose of this study is to prospectively evaluate relative effectiveness of high dose influenza vaccine in preventing influenza mortality, hospitalization, and functional decline in a nursing home population in the U.S., compared to the standard dose trivalent seasonal influenza vaccine.

Condition or disease	Intervention/treatment	Phase
Influenza	Biological: HD Vaccine; Biological: SD Vaccine; Biological: Free Vaccine; Biological: Usual Care	Phase 4

Detailed Description:

SUMMARY: This nationally representative study samples from estimated 6782 Medicare-certified nursing homes co-located within 50 miles of the 122 cities reporting to Center for Disease Control and Prevention (CDC) weekly influenza surveillance. In total, 1000 facilities will be enrolled for random assignment to either: 1) the licensed high dose (HD) trivalent influenza vaccine (High-Dose Fluzone [HD vaccine]), or 2) the standard dose (SD) trivalent influenza vaccine (Fluzone [SD vaccine]) for their residents. Additionally, half the facilities will receive free SD vaccine for their staff and the remaining facilities will practice usual care (no free vaccine) for staff.

BACKGROUND: Influenza and pneumonia (P&I) are leading infectious causes of hospitalization and mortality in community-dwelling older adults and residents of long-term custodial care facilities or nursing homes (NH), and produce substantial annual health care costs. The elderly incur over 90% of this disease burden and NH residents are especially vulnerable given immune senescence, multimorbidity, and close living quarters. While hospitalization rates for NH residents vary considerably between facilities, most occur during the sixteen weeks of peak influenza activity annually. Influenza vaccination, a mainstay in prevention, is recommended in the U.S. for all individuals six months of age and older. Vaccination associates with reduced rates of stroke, heart attack, hospitalization, and death in non-institutional older adult populations. However, the benefit of influenza vaccine for the elderly in general has been questioned, a salient concern for frail elderly, such as NH residents. Influenza vaccination rates vary substantially between nursing homes. Influenza vaccine response declines with advancing age, indicating the need for a better vaccine.

OBJECTIVES: The primary objective is to estimate the differences in all-cause hospitalization rates during influenza season experienced by long-stay nursing home residents, between facilities using HD vaccine vs. SD vaccine. The secondary objective is to estimate the differences in the likelihood of Activities of Daily Living (ADL) functional decline and mortality rates in the study nursing homes.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	823 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	High Dose Influenza Vaccination and Morbidity & Mortality in U.S. Nursing Homes
Study Start Date :	February 2013
Actual Primary Completion Date :	July 20, 2017
Estimated Study Completion Date :	May 2018

Arms and Interventions

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Arm	Intervention/treatment
Experimental: HD Vaccine (Residents) + Free Vaccine (Staff); NH facilities randomized to receive high-dose trivalent influenza vaccine (Fluzone High-Dose) for the residents and provided free SD vaccine (Fluzone) for the staff.	Biological: HD Vaccine; Nursing home residents over 65 years are allocated to receive high-dose vaccine. Residents under 65 years are provided standard-dose vaccine.; Other Name: Fluzone High-Dose; Biological: Free Vaccine; Nursing home facilities are provided free standard-dose vaccine for their staff.; Other Name: Fluzone
Experimental: HD Vaccine (Residents) + Usual Care (Staff); NH facilities randomized to receive high-dose trivalent influenza vaccine (Fluzone High-Dose) for the residents and not provided free vaccine for the staff.	Biological: HD Vaccine; Nursing home residents over 65 years are allocated to receive high-dose vaccine. Residents under 65 years are provided standard-dose vaccine.; Other Name: Fluzone High-Dose; Biological: Usual Care; Nursing home staff will have access to influenza vaccine, per standard of care. No free vaccine provided as part of study.
Active Comparator: SD Vaccine (Residents) + Free Vaccine (Staff); NH facilities randomized to receive standard dose influenza vaccine (Fluzone) for the residents and provided free standard dose vaccine (Fluzone) for the staff.	Biological: SD Vaccine; Nursing home residents are allocated to receive standard-dose vaccine.; Other Name: Fluzone; Biological: Free Vaccine; Nursing home facilities are provided free standard-dose vaccine for their staff.; Other Name: Fluzone
Active Comparator: SD Vaccine (Residents) + Usual Care (Staff); NH facilities randomized to receive standard dose influenza vaccine (Fluzone) for the residents and not provided free vaccine for the staff.	Biological: SD Vaccine; Nursing home residents are allocated to receive standard-dose vaccine.; Other Name: Fluzone; Biological: Usual Care; Nursing home staff will have access to influenza vaccine, per standard of care. No free vaccine provided as part of study.

Outcome Measures

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Primary Outcome Measures :

1. Hospitalization rate [ Time Frame: up to 1 year ]

Secondary Outcome Measures :

1. Change in activities of daily living (ADL) scores [ Time Frame: up to 1 year ]
2. Facility-level mortality rate [ Time Frame: up to 1 year ]
3. Hospitalization rate based on vaccine type and influenza strain [ Time Frame: Up to 3 years ]
4. Cost difference between vaccine types [ Time Frame: up to 3 years ]
5. Effect of facility policies on staff vaccination rates [ Time Frame: up to 3 years ]

Other Outcome Measures:

1. Difference in hospitalization claims based on staff vaccination status [ Time Frame: up to 1 year ]
   Effect on clinical outcomes of nursing home residents based on staff vaccine uptake.

Eligibility Criteria

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Ages Eligible for Study:	65 Years and older (Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

• Long-term care facilities within 50 miles of one of the 122 cities that serve as CDC surveillance sites

Exclusion Criteria:

• Facilities already systematically administering HD vaccine to their residents
• Facilities having fewer than 50 long-stay residents
• Hospital-based facilities
• Facilities with more than 20% of the population under age 65
• Facilities not submitting Minimum Data Set (MDS) data

Contacts and Locations

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Locations

United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
United States, Rhode Island
Brown University
Providence, Rhode Island, United States, 02912
United States, Virginia
Insight Therapeutics, LLC
Norfolk, Virginia, United States, 23510

Sponsors and Collaborators

Insight Therapeutics, LLC

Brown University

Case Western Reserve University

Investigators

Principal Investigator:	Stefan Gravenstein, MD, MPH	Case Western Reserve University
Principal Investigator:	Vincent Mor, PhD	Brown University
Principal Investigator:	Ed Davidson, PharmD, MPH	Insight Therapeutics, LLC

More Information

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Study Data/Documents: Study Protocol 

Identifier: doi: 10.1177/1740774515625976

We have published our study design and rationale in Clinical Trials Journal. Citation is below.

Stefan Gravenstein, Roshani Dahal, Pedro L Gozalo, H Edward Davidson, Lisa F Han, Monica Taljaard, and Vincent Mor. A cluster randomized controlled trial comparing relative effectiveness of two licensed influenza vaccines in US nursing homes: Design and rationale. Clin Trials 1740774515625976, first published on February 11, 2016 doi:10.1177/1740774515625976

Publications:

Gozalo PL, Pop-Vicas A, Feng Z, Gravenstein S, Mor V. Effect of influenza on functional decline. J Am Geriatr Soc. 2012 Jul;60(7):1260-7. doi: 10.1111/j.1532-5415.2012.04048.x. Epub 2012 Jun 21.

Fiore AE, Shay DK, Haber P, Iskander JK, Uyeki TM, Mootrey G, Bresee JS, Cox NJ; Advisory Committee on Immunization Practices (ACIP), Centers for Disease Control and Prevention (CDC). Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007. MMWR Recomm Rep. 2007 Jul 13;56(RR-6):1-54.

DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, Pollak R, Christoff J, Earl J, Landolfi V, Martin E, Gurunathan S, Nathan R, Greenberg DP, Tornieporth NG, Decker MD, Talbot HK. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014 Aug 14;371(7):635-45. doi: 10.1056/NEJMoa1315727.

Keitel WA, Atmar RL, Cate TR, Petersen NJ, Greenberg SB, Ruben F, Couch RB. Safety of high doses of influenza vaccine and effect on antibody responses in elderly persons. Arch Intern Med. 2006 May 22;166(10):1121-7.

Falsey AR, Treanor JJ, Tornieporth N, Capellan J, Gorse GJ. Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. J Infect Dis. 2009 Jul 15;200(2):172-80. doi: 10.1086/599790.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gravenstein S, Davidson HE, Taljaard M, Ogarek J, Gozalo P, Han L, Mor V. Comparative effectiveness of high-dose versus standard-dose influenza vaccination on numbers of US nursing home residents admitted to hospital: a cluster-randomised trial. Lancet Respir Med. 2017 Sep;5(9):738-746. doi: 10.1016/S2213-2600(17)30235-7. Epub 2017 Jul 20.

Gravenstein S, Dahal R, Gozalo PL, Davidson HE, Han LF, Taljaard M, Mor V. A cluster randomized controlled trial comparing relative effectiveness of two licensed influenza vaccines in US nursing homes: Design and rationale. Clin Trials. 2016 Jun;13(3):264-74. doi: 10.1177/1740774515625976. Epub 2016 Feb 11.

Responsible Party:	Insight Therapeutics, LLC
ClinicalTrials.gov Identifier:	NCT01815268 History of Changes
Other Study ID Numbers:	GRC75-EXT
First Posted:	March 21, 2013
Last Update Posted:	November 13, 2017
Last Verified:	November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Insight Therapeutics, LLC:

Randomized Controlled Trial; Influenza; Influenza vaccine; Flu Vaccine; Fluzone; HD Fluzone; Nursing Home; Hospitalization; Mortality; Health Care worker vaccination; ADL decline	Effectiveness; Elderly; Morbidity; Nursing Home resident; Frail; Institutionalized; Epidemiology; CDC; US; city

Additional relevant MeSH terms:

Influenza, Human; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections	Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs