<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01720277</url>
  </required_header>
  <id_info>
    <org_study_id>GRC75-HD Nursing Home Pilot</org_study_id>
    <nct_id>NCT01720277</nct_id>
  </id_info>
  <brief_title>High Dose Influenza Vaccine in Nursing Home - Pilot Study</brief_title>
  <official_title>High Dose Influenza Vaccination and Morbidity and Mortality in U.S. Nursing Homes - A Pilot Evaluation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Insight Therapeutics, LLC</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Brown University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Insight Therapeutics, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this pilot evaluation is to help determine the feasibility and power needed to&#xD;
      prospectively evaluate relative effectiveness of high-dose influenza vaccine in preventing&#xD;
      influenza mortality and hospitalization in a nursing home population in the U.S., compared to&#xD;
      the standard-dose influenza vaccine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Influenza remains the most common preventable respiratory viral infection of older adults.&#xD;
      Older adults incur more than 90% of the disease burden, and those residing in nursing homes&#xD;
      are the most affected subset given their immune senescence, multi-morbidity, and close living&#xD;
      quarters. Each year, the majority of influenza-related hospitalizations occur during the&#xD;
      period with the greatest influenza activity.&#xD;
&#xD;
      Influenza vaccination has been associated with reduced hospitalization, strokes, heart&#xD;
      attacks and death in non-institutional older adult populations, but the benefit of influenza&#xD;
      vaccine for the oldest population has been questioned. The new high-dose influenza vaccine is&#xD;
      considerably more immunogenic in older adults, and has recently been approved for use in&#xD;
      individuals aged 65 years and older. No clinical data yet confirm whether the improved&#xD;
      immunogenicity translates into added clinical benefit, such as further reduction in&#xD;
      hospitalization or death. Estimating the benefit of influenza vaccination among older adults&#xD;
      in long-term care settings using randomized controlled trials requires extensive effort and&#xD;
      is costly. Instead, a pragmatic RCT in a nursing home population has several advantages as a&#xD;
      model for comparing therapeutic approaches.&#xD;
&#xD;
      This clinical trial aims to test the feasibility of our protocol for a subsequent larger&#xD;
      study. We aim to demonstrate that we can recruit and enroll facilities; randomly assign and&#xD;
      coordinate vaccine delivery; collect data; conduct site audits for data validation; create&#xD;
      outcomes using multiple data sources; and conduct analyses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">May 2013</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total All-cause Hospitalizations</measure>
    <time_frame>1 year</time_frame>
    <description>The primary outcome will establish our methodology for measuring all-cause hospitalizations using the Minimum Data Set (MDS).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Residents' Functional Status</measure>
    <time_frame>1 year</time_frame>
    <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.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Recruit, Enroll, and Randomize Nursing Homes Per Calculated Sample Size</measure>
    <time_frame>1 year</time_frame>
    <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</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2957</enrollment>
  <condition>Influenza</condition>
  <arm_group>
    <arm_group_label>HD Fluzone Vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NH facilities randomized to receive high dose trivalent influenza vaccine (HD Fluzone) for the residents.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SD Fluzone Vaccine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>NH facilities randomized to standard dose trivalent influenza vaccine (SD Fluzone) for the residents.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>HD Fluzone Vaccine</intervention_name>
    <description>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).</description>
    <arm_group_label>HD Fluzone Vaccine</arm_group_label>
    <other_name>Fluzone High Dose influenza vaccine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>SD Fluzone Vaccine</intervention_name>
    <description>Nursing home residents are allocated to receive standard trivalent vaccine (TIV).</description>
    <arm_group_label>SD Fluzone Vaccine</arm_group_label>
    <other_name>Fluzone influenza vaccine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Long-term care facilities in one of the 122 cities that serve as Center for Disease&#xD;
             Control and Prevention (CDC) surveillance sites&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Facilities already systematically administering HD vaccine to their residents&#xD;
&#xD;
          -  Facilities for whom over half the residents are on Medicare (short-stay)&#xD;
&#xD;
          -  Facilities in which over half the residents are on Medicare Part A (SNF)&#xD;
&#xD;
          -  Facilities having fewer than 50 long-stay residents&#xD;
&#xD;
          -  Hospital-based facilities&#xD;
&#xD;
          -  Facilities with more than 20% of the population under age 65&#xD;
&#xD;
          -  Facilities with mandated (employment-dependent) seasonal influenza vaccination&#xD;
&#xD;
          -  Facilities not submitting MDS data&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stefan Gravenstein, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Case Western Reserve University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ed Davidson, PharmD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Insight Therapeutics, LLC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vincent Mor, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brown University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brown Univeristy</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Insight Therapeutics</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>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. doi: 10.1001/jama.289.2.179.</citation>
    <PMID>12517228</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1001/jama.292.11.1333.</citation>
    <PMID>15367555</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1136/bmj.39010.581354.55. Epub 2006 Dec 1.</citation>
    <PMID>17142257</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1093/gerona/56.6.m391.</citation>
    <PMID>11382801</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>22724499</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1001/archinte.158.6.645.</citation>
    <PMID>9521230</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1093/ije/dyi274. Epub 2005 Dec 20.</citation>
    <PMID>16368725</PMID>
  </reference>
  <reference>
    <citation>Simonsen L, Viboud C, Taylor R. Influenza vaccination in elderly people. Lancet. 2005 Dec 17;366(9503):2086. doi: 10.1016/S0140-6736(05)67884-1. No abstract available.</citation>
    <PMID>16360785</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>17625497</PMID>
  </reference>
  <reference>
    <citation>Kingston BJ, Wright CV Jr. Influenza in the nursing home. Am Fam Physician. 2002 Jan 1;65(1):75-8, 72.</citation>
    <PMID>11804444</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1007/BF03405054.</citation>
    <PMID>12583681</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>21496257</PMID>
  </reference>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>October 15, 2012</study_first_submitted>
  <study_first_submitted_qc>October 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 2, 2012</study_first_posted>
  <results_first_submitted>June 15, 2017</results_first_submitted>
  <results_first_submitted_qc>March 20, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">April 18, 2018</results_first_posted>
  <last_update_submitted>April 25, 2018</last_update_submitted>
  <last_update_submitted_qc>April 25, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brown University</investigator_affiliation>
    <investigator_full_name>Stefan Gravenstein, MD, MPH</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Randomized Controlled Trial</keyword>
  <keyword>Influenza</keyword>
  <keyword>Influenza vaccine</keyword>
  <keyword>Flu Vaccine</keyword>
  <keyword>Fluzone</keyword>
  <keyword>HD Fluzone</keyword>
  <keyword>Nursing Homes</keyword>
  <keyword>Hospitalization</keyword>
  <keyword>Mortality</keyword>
  <keyword>Health Care worker vaccination</keyword>
  <keyword>ADL decline</keyword>
  <keyword>Pilot</keyword>
  <keyword>Effectiveness</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_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.&#xD;
Subject--Eligible nursing home residents in each participating facility.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>High-Dose Vaccine for Residents</title>
          <description>NH facilities randomized to receive high dose trivalent influenza vaccine (High-dose Fluzone) for the residents.</description>
        </group>
        <group group_id="P2">
          <title>Standard-dose for Residents</title>
          <description>NH facilities randomized to receive free standard-dose trivalent influenza vaccine (Fluzone) for nursing home residents.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1461"/>
                <participants group_id="P2" count="1496"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="958">intent-to-treat approach</participants>
                <participants group_id="P2" count="938">intent-to-treat approach</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="503"/>
                <participants group_id="P2" count="558"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Characteristics of participating facilities that met our inclusion criteria and were randomized.&#xD;
Residents in each participating facility were offered influenza vaccine according to the randomization.</population>
      <group_list>
        <group group_id="B1">
          <title>High-Dose Vaccine for Residents</title>
          <description>NH facilities randomized to receive high dose trivalent influenza vaccine (High-dose Fluzone) for the residents.</description>
        </group>
        <group group_id="B2">
          <title>Standard-dose for Residents</title>
          <description>NH facilities randomized to receive free standard-dose trivalent influenza vaccine (Fluzone) for nursing home residents.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1461"/>
            <count group_id="B2" value="1496"/>
            <count group_id="B3" value="2957"/>
          </count_list>
        </analyzed>
        <analyzed>
          <units>nursing homes</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
            <count group_id="B2" value="19"/>
            <count group_id="B3" value="39"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <title>Average age</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="84.5" spread="8.4"/>
                    <measurement group_id="B2" value="83.4" spread="8.7"/>
                    <measurement group_id="B3" value="84.0" spread="8.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <title>Percent of female nursing home residents</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1094"/>
                    <measurement group_id="B2" value="1113"/>
                    <measurement group_id="B3" value="2207"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of residents per nursing home</title>
          <units>participants</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="108" spread="49"/>
                    <measurement group_id="B2" value="124" spread="54"/>
                    <measurement group_id="B3" value="116" spread="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Percent of residents who are long-stay</title>
          <units>percent</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="88.0" spread="6.5"/>
                    <measurement group_id="B2" value="86.5" spread="12.1"/>
                    <measurement group_id="B3" value="87.2" spread="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of long-stay residents who are over 65 years of age</title>
          <units>participants</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="78" spread="37"/>
                    <measurement group_id="B2" value="78" spread="44"/>
                    <measurement group_id="B3" value="78" spread="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Percent of residents with Medicaid as payer</title>
          <units>percent</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.5" spread="12.8"/>
                    <measurement group_id="B2" value="62.9" spread="17.4"/>
                    <measurement group_id="B3" value="62.7" spread="15.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Percent of residents in for-profit nursing facilities</title>
          <units>percent</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.0" spread="47.0"/>
                    <measurement group_id="B2" value="73.6" spread="45.2"/>
                    <measurement group_id="B3" value="71.8" spread="45.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of nursing facilities that are part of a chain</title>
          <units>nursing homes</units>
          <param>Number</param>
          <units_analyzed>nursing homes</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Total All-cause Hospitalizations</title>
        <description>The primary outcome will establish our methodology for measuring all-cause hospitalizations using the Minimum Data Set (MDS).</description>
        <time_frame>1 year</time_frame>
        <population>We identified long-stay nursing home residents and evaluated outcomes (e.g. hospitalizations, functional status).</population>
        <group_list>
          <group group_id="O1">
            <title>High-Dose Vaccine for Residents</title>
            <description>NH facilities randomized to receive high dose trivalent influenza vaccine (High-dose Fluzone) for the residents.</description>
          </group>
          <group group_id="O2">
            <title>Standard-dose for Residents</title>
            <description>NH facilities randomized to receive free standard-dose trivalent influenza vaccine (Fluzone) for nursing home residents.</description>
          </group>
        </group_list>
        <measure>
          <title>Total All-cause Hospitalizations</title>
          <description>The primary outcome will establish our methodology for measuring all-cause hospitalizations using the Minimum Data Set (MDS).</description>
          <population>We identified long-stay nursing home residents and evaluated outcomes (e.g. hospitalizations, functional status).</population>
          <units>events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1461"/>
                <count group_id="O2" value="1496"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="197"/>
                    <measurement group_id="O2" value="301"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Residents' Functional Status</title>
        <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.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>HD Fluzone Vaccine</title>
            <description>NH facilities randomized to receive high dose trivalent influenza vaccine (HD Fluzone) for the residents.&#xD;
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).</description>
          </group>
          <group group_id="O2">
            <title>SD Fluzone Vaccine</title>
            <description>NH facilities randomized to standard dose trivalent influenza vaccine (SD Fluzone) for the residents.&#xD;
SD Fluzone Vaccine: Nursing home residents are allocated to receive standard trivalent vaccine (TIV).</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Residents' Functional Status</title>
          <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.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1461"/>
                <count group_id="O2" value="1496"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="196"/>
                    <measurement group_id="O2" value="206"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Recruit, Enroll, and Randomize Nursing Homes Per Calculated Sample Size</title>
        <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</description>
        <time_frame>1 year</time_frame>
        <population>Nursing home facilities randomized to receive high dose or standard dose vaccine.</population>
        <group_list>
          <group group_id="O1">
            <title>HD Fluzone Vaccine</title>
            <description>NH facilities randomized to receive high dose trivalent influenza vaccine (HD Fluzone) for the residents.&#xD;
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).</description>
          </group>
          <group group_id="O2">
            <title>SD Fluzone Vaccine</title>
            <description>NH facilities randomized to standard dose trivalent influenza vaccine (SD Fluzone) for the residents.&#xD;
SD Fluzone Vaccine: Nursing home residents are allocated to receive standard trivalent vaccine (TIV).</description>
          </group>
        </group_list>
        <measure>
          <title>Recruit, Enroll, and Randomize Nursing Homes Per Calculated Sample Size</title>
          <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</description>
          <population>Nursing home facilities randomized to receive high dose or standard dose vaccine.</population>
          <units>Nursing Homes</units>
          <param>Number</param>
          <units_analyzed>Nursing Homes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Nursing Homes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The study did not collect adverse events.</time_frame>
      <desc>The study did not collect adverse events.</desc>
      <group_list>
        <group group_id="E1">
          <title>High-Dose Vaccine for Residents</title>
          <description>NH facilities randomized to receive high dose trivalent influenza vaccine (High-dose Fluzone) for the residents.</description>
        </group>
        <group group_id="E2">
          <title>Standard-dose for Residents</title>
          <description>NH facilities randomized to receive free standard-dose trivalent influenza vaccine (Fluzone) for nursing home residents.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="249" subjects_at_risk="1461"/>
                <counts group_id="E2" subjects_affected="274" subjects_at_risk="1496"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>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. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Stefan Gravenstein</name_or_title>
      <organization>Brown University and Providence VA Medical Center</organization>
      <phone>401-863-3172</phone>
      <email>Stefan_gravenstein@brown.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01720277
org study id: GRC75-HD Nursing Home Pilot
nct id: NCT01720277
lead sponsor: 
collaborator: 
has dmc: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Outcomes Assessor)
measure: Total All-cause Hospitalizations
time frame: 1 year
description: The primary outcome will establish our methodology for measuring all-cause hospitalizations using the Minimum Data Set (MDS).
measure: Change in Residents' Functional Status
time frame: 1 year
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.
measure: Recruit, Enroll, and Randomize Nursing Homes Per Calculated Sample Size
time frame: 1 year
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
arm group label: HD Fluzone Vaccine
arm group type: Experimental
description: NH facilities randomized to receive high dose trivalent influenza vaccine (HD Fluzone) for the residents.
arm group label: SD Fluzone Vaccine
arm group type: Active Comparator
description: NH facilities randomized to standard dose trivalent influenza vaccine (SD Fluzone) for the residents.
intervention type: Biological
intervention name: HD Fluzone Vaccine
description: 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).
arm group label: HD Fluzone Vaccine
other name: Fluzone High Dose influenza vaccine
intervention type: Biological
intervention name: SD Fluzone Vaccine
description: Nursing home residents are allocated to receive standard trivalent vaccine (TIV).
arm group label: SD Fluzone Vaccine
other name: Fluzone influenza vaccine
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Stefan Gravenstein, MD, MPH
role: Principal Investigator
affiliation: Case Western Reserve University
last name: Ed Davidson, PharmD, MPH
role: Principal Investigator
affiliation: Insight Therapeutics, LLC
last name: Vincent Mor, PhD
role: Principal Investigator
affiliation: Brown University
facility: 
facility: 
country: United States
citation: 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. doi: 10.1001/jama.289.2.179.
PMID: 12517228
citation: 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. doi: 10.1001/jama.292.11.1333.
PMID: 15367555
citation: 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. doi: 10.1136/bmj.39010.581354.55. Epub 2006 Dec 1.
PMID: 17142257
citation: 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. doi: 10.1093/gerona/56.6.m391.
PMID: 11382801
citation: 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.
PMID: 22724499
citation: 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. doi: 10.1001/archinte.158.6.645.
PMID: 9521230
citation: 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. doi: 10.1093/ije/dyi274. Epub 2005 Dec 20.
PMID: 16368725
citation: Simonsen L, Viboud C, Taylor R. Influenza vaccination in elderly people. Lancet. 2005 Dec 17;366(9503):2086. doi: 10.1016/S0140-6736(05)67884-1. No abstract available.
PMID: 16360785
citation: 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.
PMID: 17625497
citation: Kingston BJ, Wright CV Jr. Influenza in the nursing home. Am Fam Physician. 2002 Jan 1;65(1):75-8, 72.
PMID: 11804444
citation: 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. doi: 10.1007/BF03405054.
PMID: 12583681
citation: 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.
PMID: 21496257
responsible party type: Principal Investigator
investigator affiliation: Brown University
investigator full name: Stefan Gravenstein, MD, MPH
investigator title: Professor
mesh term: Influenza, Human
mesh term: Vaccines
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 