High Dose Influenza Vaccine in Nursing Home - Pilot Study

• Sponsor: Insight Therapeutics, LLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT01720277
• Collaborator: Brown University (Other)
• Enrollment: 2,957
• Locations: 2
• Arms: 2
• Duration (Months): 44
• Patients Per Site: 1478.5
• Patients Per Site Per Month: 33.6

Study Details

Study Description

Brief Summary

The purpose of this pilot evaluation is to help determine the feasibility and power needed to prospectively evaluate relative effectiveness of high-dose influenza vaccine in preventing influenza mortality and hospitalization in a nursing home population in the U.S., compared to the standard-dose influenza vaccine.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: HD Fluzone Vaccine; Biological: SD Fluzone Vaccine	Phase 4

Detailed Description

Influenza remains the most common preventable respiratory viral infection of older adults. Older adults incur more than 90% of the disease burden, and those residing in nursing homes are the most affected subset given their immune senescence, multi-morbidity, and close living quarters. Each year, the majority of influenza-related hospitalizations occur during the period with the greatest influenza activity.

Influenza vaccination has been associated with reduced hospitalization, strokes, heart attacks and death in non-institutional older adult populations, but the benefit of influenza vaccine for the oldest population has been questioned. The new high-dose influenza vaccine is considerably more immunogenic in older adults, and has recently been approved for use in individuals aged 65 years and older. No clinical data yet confirm whether the improved immunogenicity translates into added clinical benefit, such as further reduction in hospitalization or death. Estimating the benefit of influenza vaccination among older adults in long-term care settings using randomized controlled trials requires extensive effort and is costly. Instead, a pragmatic RCT in a nursing home population has several advantages as a model for comparing therapeutic approaches.

This clinical trial aims to test the feasibility of our protocol for a subsequent larger study. We aim to demonstrate that we can recruit and enroll facilities; randomly assign and coordinate vaccine delivery; collect data; conduct site audits for data validation; create outcomes using multiple data sources; and conduct analyses.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2957 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: High Dose Influenza Vaccination and Morbidity and Mortality in U.S. Nursing Homes - A Pilot Evaluation
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HD Fluzone Vaccine NH facilities randomized to receive high dose trivalent influenza vaccine (HD Fluzone) for the residents.	Biological: HD Fluzone Vaccine; Nursing home residents over 65 years are allocated to receive high dose trivalent vaccine. Residents under 65 years are provided standard dose trivalent vaccine (TIV).; Other Names: Fluzone High Dose influenza vaccine
Active Comparator: SD Fluzone Vaccine NH facilities randomized to standard dose trivalent influenza vaccine (SD Fluzone) for the residents.	Biological: SD Fluzone Vaccine; Nursing home residents are allocated to receive standard trivalent vaccine (TIV).; Other Names: Fluzone influenza vaccine

Outcome Measures

Primary Outcome Measures

1. Total All-cause Hospitalizations [1 year]

   The primary outcome will establish our methodology for measuring all-cause hospitalizations using the Minimum Data Set (MDS).

Secondary Outcome Measures

1. Change in Residents' Functional Status [1 year]

   The secondary outcome will establish our methodology for measuring change in functional status of nursing home residents using Activities of Daily Living (ADL) data in the Minimum Data Set (MDS). A change in functional status is defined as a decline in physical functioning by at least 4 points on the 28-point ADL scale.

Other Outcome Measures

1. Recruit, Enroll, and Randomize Nursing Homes Per Calculated Sample Size [1 year]

   This outcome evaluates our ability to recruit and enroll nursing facilities that meet our inclusion and exclusion criteria, and ensure nursing home residents receive either high-dose or standard-dose influenza vaccine

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Long-term care facilities in one of the 122 cities that serve as Center for Disease Control and Prevention (CDC) surveillance sites

Exclusion Criteria:

• Facilities already systematically administering HD vaccine to their residents

• Facilities for whom over half the residents are on Medicare (short-stay)

• Facilities in which over half the residents are on Medicare Part A (SNF)

• Facilities having fewer than 50 long-stay residents

• Hospital-based facilities

• Facilities with more than 20% of the population under age 65

• Facilities with mandated (employment-dependent) seasonal influenza vaccination

• Facilities not submitting MDS data

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brown Univeristy	Providence	Rhode Island	United States	02903
2	Insight Therapeutics	Norfolk	Virginia	United States	23510

Sponsors and Collaborators

• Insight Therapeutics, LLC
• Brown University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

• Barker WH, Borisute H, Cox C. A study of the impact of influenza on the functional status of frail older people. Arch Intern Med. 1998 Mar 23;158(6):645-50.
• Deguchi Y, Nishimura K. Efficacy of Influenza Vaccine in Elderly Persons in Welfare Nursing Homes: Reduction in Risks of Mortality and Morbidity During an Influenza A (H3N2) Epidemic. J Gerontol A Biol Sci Med Sci. 2001 Jun;56(6):M391-4.
• 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.
• 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.
• Hayward AC, Harling R, Wetten S, Johnson AM, Munro S, Smedley J, Murad S, Watson JM. Effectiveness of an influenza vaccine programme for care home staff to prevent death, morbidity, and health service use among residents: cluster randomised controlled trial. BMJ. 2006 Dec 16;333(7581):1241. Epub 2006 Dec 1.
• Jackson LA, Jackson ML, Nelson JC, Neuzil KM, Weiss NS. Evidence of bias in estimates of influenza vaccine effectiveness in seniors. Int J Epidemiol. 2006 Apr;35(2):337-44. Epub 2005 Dec 20.
• Kingston BJ, Wright CV Jr. Influenza in the nursing home. Am Fam Physician. 2002 Jan 1;65(1):75-8, 72.
• Menec VH, Black C, MacWilliam L, Aoki FY. The impact of influenza-associated respiratory illnesses on hospitalizations, physician visits, emergency room visits, and mortality. Can J Public Health. 2003 Jan-Feb;94(1):59-63.
• Mor V, Intrator O, Unruh MA, Cai S. Temporal and Geographic variation in the validity and internal consistency of the Nursing Home Resident Assessment Minimum Data Set 2.0. BMC Health Serv Res. 2011 Apr 15;11:78. doi: 10.1186/1472-6963-11-78.
• Simonsen L, Viboud C, Taylor R. Influenza vaccination in elderly people. Lancet. 2005 Dec 17;366(9503):2086.
• Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ, Fukuda K. Influenza-associated hospitalizations in the United States. JAMA. 2004 Sep 15;292(11):1333-40.
• Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003 Jan 8;289(2):179-86.

• Responsible Party: Stefan Gravenstein, MD, MPH, Professor, Brown University
• ClinicalTrials.gov Identifier: NCT01720277
• Other Study ID Numbers: GRC75-HD Nursing Home Pilot
• First Posted: Nov 2, 2012
• Last Update Posted: May 23, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Stefan Gravenstein, MD, MPH, Professor, Brown University: Randomized Controlled Trial; Influenza; Influenza vaccine; Flu Vaccine; Fluzone; HD Fluzone; Nursing Homes; Hospitalization; Mortality; Health Care worker vaccination; ADL decline; Pilot; Effectiveness
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

Participant Flow

Recruitment Details	Cluster--We included nursing homes (NHs) within 50 miles of a CDC surveillance. We identified and contacted individual facilities and organizations. Each recruited NH completed a site feasibility form and was notified of its eligibility based on the exclusion criteria. Subject--Eligible nursing home residents in each participating facility.

Arm/Group Title	High-Dose Vaccine for Residents	Standard-dose for Residents
Arm/Group Description	NH facilities randomized to receive high dose trivalent influenza vaccine (High-dose Fluzone) for the residents.	NH facilities randomized to receive free standard-dose trivalent influenza vaccine (Fluzone) for nursing home residents.
Period Title: Overall Study
STARTED	1461	1496
COMPLETED	958	938
NOT COMPLETED	503	558

Baseline Characteristics

Arm/Group Title	High-Dose Vaccine for Residents	Standard-dose for Residents	Total
Arm/Group Description	NH facilities randomized to receive high dose trivalent influenza vaccine (High-dose Fluzone) for the residents.	NH facilities randomized to receive free standard-dose trivalent influenza vaccine (Fluzone) for nursing home residents.	Total of all reporting groups
Overall Participants	1461	1496	2957
Overall nursing homes	20	19	39
Age, Customized (years) [Mean (Standard Deviation) ]
Average age	84.5 (8.4)	83.4 (8.7)	84.0 (8.6)
Sex/Gender, Customized (Count of Participants)
Percent of female nursing home residents	1094 74.9%	1113 74.4%	2207 74.6%
Number of residents per nursing home (participants) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [participants]	108 (49) 7.4%	124 (54) 8.3%	116 (51) 3.9%
Percent of residents who are long-stay (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]	88.0 (6.5)	86.5 (12.1)	87.2 (9.7)
Number of long-stay residents who are over 65 years of age (participants) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [participants]	78 (37) 5.3%	78 (44) 5.2%	78 (40) 2.6%
Percent of residents with Medicaid as payer (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]	62.5 (12.8)	62.9 (17.4)	62.7 (15.0)
Percent of residents in for-profit nursing facilities (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]	70.0 (47.0)	73.6 (45.2)	71.8 (45.6)
Number of nursing facilities that are part of a chain (nursing homes) [Number]
Number [nursing homes]	10	6	16

Outcome Measures

1. Primary Outcome

Title	Total All-cause Hospitalizations
Description	The primary outcome will establish our methodology for measuring all-cause hospitalizations using the Minimum Data Set (MDS).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

We identified long-stay nursing home residents and evaluated outcomes (e.g. hospitalizations, functional status).

Arm/Group Title	High-Dose Vaccine for Residents	Standard-dose for Residents
Arm/Group Description	NH facilities randomized to receive high dose trivalent influenza vaccine (High-dose Fluzone) for the residents.	NH facilities randomized to receive free standard-dose trivalent influenza vaccine (Fluzone) for nursing home residents.
Measure Participants	1461	1496
Number [events]	197	301

2. Secondary Outcome

Title	Change in Residents' Functional Status
Description	The secondary outcome will establish our methodology for measuring change in functional status of nursing home residents using Activities of Daily Living (ADL) data in the Minimum Data Set (MDS). A change in functional status is defined as a decline in physical functioning by at least 4 points on the 28-point ADL scale.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HD Fluzone Vaccine	SD Fluzone Vaccine
Arm/Group Description	NH facilities randomized to receive high dose trivalent influenza vaccine (HD Fluzone) for the residents. HD Fluzone Vaccine: Nursing home residents over 65 years are allocated to receive high dose trivalent vaccine. Residents under 65 years are provided standard dose trivalent vaccine (TIV).	NH facilities randomized to standard dose trivalent influenza vaccine (SD Fluzone) for the residents. SD Fluzone Vaccine: Nursing home residents are allocated to receive standard trivalent vaccine (TIV).
Measure Participants	1461	1496
Count of Participants [Participants]	196 13.4%	206 13.8%

3. Other Pre-specified Outcome

Title	Recruit, Enroll, and Randomize Nursing Homes Per Calculated Sample Size
Description	This outcome evaluates our ability to recruit and enroll nursing facilities that meet our inclusion and exclusion criteria, and ensure nursing home residents receive either high-dose or standard-dose influenza vaccine
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Nursing home facilities randomized to receive high dose or standard dose vaccine.

Arm/Group Title	HD Fluzone Vaccine	SD Fluzone Vaccine
Arm/Group Description	NH facilities randomized to receive high dose trivalent influenza vaccine (HD Fluzone) for the residents. HD Fluzone Vaccine: Nursing home residents over 65 years are allocated to receive high dose trivalent vaccine. Residents under 65 years are provided standard dose trivalent vaccine (TIV).	NH facilities randomized to standard dose trivalent influenza vaccine (SD Fluzone) for the residents. SD Fluzone Vaccine: Nursing home residents are allocated to receive standard trivalent vaccine (TIV).
Measure Participants	20	19
Measure Nursing Homes	20	19
Number [Nursing Homes]	20	19

Adverse Events

Time Frame	The study did not collect adverse events.
Adverse Event Reporting Description	The study did not collect adverse events.
Arm/Group Title	High-Dose Vaccine for Residents		Standard-dose for Residents
Arm/Group Description	NH facilities randomized to receive high dose trivalent influenza vaccine (High-dose Fluzone) for the residents.		NH facilities randomized to receive free standard-dose trivalent influenza vaccine (Fluzone) for nursing home residents.
All Cause Mortality
	High-Dose Vaccine for Residents		Standard-dose for Residents
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	249/1461 (17%)		274/1496 (18.3%)
Serious Adverse Events
	High-Dose Vaccine for Residents		Standard-dose for Residents
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	High-Dose Vaccine for Residents		Standard-dose for Residents
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.