Test-and-treat for Influenza in Homeless Shelters

• ClinicalTrials.gov Identifier: NCT04141917
• Recruitment Status: Terminated
• First Posted: October 28, 2019
• Last Update Posted: July 20, 2021
• Sponsor: University of Washington
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Helen Chu, University of Washington

Study Description

Brief Summary:

This study is a stepped-wedge cluster-randomized trial of on-site rapid testing and treatment for influenza in homeless shelters within the Seattle area to determine whether this strategy reduced the incidence of influenza in the shelter environment.

Condition or disease	Intervention/treatment	Phase
Influenza; Respiratory Viral Infection	Combination Product: Point-of-care molecular testing and treatment of influenza	Phase 4

Detailed Description:

The study will be conducted over the course of two flu seasons, and all shelters will start with routine surveillance of influenza using mid-turbinate nasal swabs for sample collection and RT-PCR testing. Shelters will be randomized to implement a test-and-treat strategy at different months throughout flu season, treating individuals who present ARI symptoms or new or worsening cough within 2 days (48 hours). Shelters will continue routine surveillance until all offer the test-and-treat strategy. Eligible individuals will be tested on site with a point-of-care molecular influenza test and, if positive, offered antiviral treatment. Individuals with 3-7 days of symptoms, or who choose not to participate in the intervention strategy, will still be eligible for participation in the routine surveillance.

Our primary hypothesis is that implementation of a point-of-care diagnostic and antiviral treatment intervention among sheltered individuals experiencing homelessness will reduce the incidence of influenza within this population over the course of a flu season. A process evaluation will also be conducted to explore the feasibility of point-of-care testing implementation in this population.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1222 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Stepped-wedge Design Study of Point-of-care Molecular Testing for Influenza and Treatment With Baloxavir for Prevention of Secondary Transmission of Influenza in Homeless Shelters in Seattle, WA
• Actual Study Start Date: November 15, 2019
• Actual Primary Completion Date: March 31, 2021
• Actual Study Completion Date: March 31, 2021

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Standard influenza surveillance; Subjects exhibiting ≥ 2 ARI symptoms or new or worsening cough in the last 7 days at a participating shelter complete a survey collecting demographic and clinical data, and provide a mid-turbinate nasal swab for RT-PCR testing.
Active Comparator: Point-of-care molecular testing and treatment of influenza; Subjects exhibiting ≥ 2 ARI symptoms, or new or worsening cough, in the last 48 hrs at a participating shelter complete a survey collecting demographic and clinical data, and provide a mid-turbinate nasal swab to be tested on-site with a molecular assay (Abbott ID NOW™ Influenza A & B (Chicago, IL)) and receive an antiviral if tested positive (XOFLUZA™ or Tamiflu®) .	Combination Product: Point-of-care molecular testing and treatment of influenza; Eligible individuals will be tested on site with a point-of-care molecular influenza test and, if positive, offered antiviral treatment with baloxavir for those aged ≥12 years, or oseltamivir for those aged <12 years; pregnant; breastfeeding; liver disease; or are immunosuppressed. Follow-up nasal swabs and symptom diaries will be collected from participants 2 or 3 days after receiving the antiviral, and again 5, 6, or 7 days after receiving.

Outcome Measures

Primary Outcome Measures :

1. Incidence of cases of influenza in shelters during the intervention period compared to the control period. [ Time Frame: Up to 24 months ]
   Calculated as the number of cases of laboratory-confirmed influenza among shelter residents per person-day of observations (person-days of observation will be based on the daily census at the shelter). The incidence during intervention periods will be compared to the incidence during non-intervention periods using general estimating equation models to control for clustering, differences in shelters, and time period.

Secondary Outcome Measures :

1. Feasibility of implementation of point-of-care molecular testing and treatment of influenza in shelters, [ Time Frame: Up to 24 months ]
   Time between symptom onset until diagnosis
2. Feasibility of implementation of influenza treatment in shelters [ Time Frame: Up to 24 months ]
   Time between symptom onset until treatment
3. Cost effectiveness of test-and-treat intervention in shelters [ Time Frame: Up to 24 months ]
   Assessed using health resource utilization (including emergency department visits) and school and work absenteeism among influenza cases before and after the intervention, incorporating cost of test-and-treat infrastructure
4. Proportion of participants that drop out of study [ Time Frame: Up to 24 months ]
   Measured as dropping out after providing consent
5. Proportion of participants that show non-compliance with study drug [ Time Frame: Up to 24 months ]
   Only applicable to those that receive oseltamivir rather than baloxavir which is a single-dose antiviral. Measured based on self-report during follow-up visits with study research assistants.
6. Total number of person-tests per census-day at shelters among residents that are eligible for testing [ Time Frame: Up to 24 months ]
   Census for each shelter available daily
7. Symptom type, duration and severity among influenza-positive cases [ Time Frame: Up to 24 months ]
   Descriptive statistics of clinical manifestations of illness, stratified by demographic, comorbidity, and stain-specific data
8. Point prevalence of clinical, demographic, and behavioral factors associated with asymptomatic influenza-positive cases [ Time Frame: Up to 24 months ]
   Monthly participation of asymptomatic subjects
9. Proportion of laboratory-confirmed influenza cases that report fever [ Time Frame: Up to 24 months ]
   Based on self-report, not gold standard measurement
10. Comparison of symptoms type, duration, and severity between season influenza vaccinated and unvaccinated subjects with an influenza-positive test result [ Time Frame: Up to 24 months ]
    Based on self-report
11. Viral titer [ Time Frame: Up to 24 months ]
    Measured for each sample collection
12. Proportion of samples with detectable influenza RNA virus at days 2/3 and days 5/6/7 [ Time Frame: Up to 24 months ]
    Provided subject has not become lost to follow up
13. Proportion of cases in the shelter that are found via sequencing to be secondary cases, and proportion that are community-acquired [ Time Frame: Up to 24 months ]
    Assessed by genetic sequencing of influenza strains
14. Emergence of antiviral resistance [ Time Frame: Up to 24 months ]
    Assessed by genetic sequencing of influenza strains

Eligibility Criteria

• Ages Eligible for Study: 3 Months and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Resident for 1 or more days at a participating shelter
• ≥2 ARI symptoms or acute cough alone
• Willing to take study medication
• Willing to comply with all study procedures, including weekly surveillance and repeat nasal swab at day 2/3 and day 5/6/7 post-treatment
• Able to provide written, informed consent and/or assent

Exclusion Criteria:

• Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration
• Inability to consent and/or comply with study protocol
• Individuals who have received oseltamivir or baloxavir within past 7 days for treatment of influenza
• Individuals with known hypersensitivity to baloxavir marboxil or oseltamivir
• Individuals with chronic kidney disease

Contacts and Locations

Locations

United States, Washington

Mary's Place Burien

Burien, Washington, United States, 98146

Compass Housing Alliance at First Presbyterian

Seattle, Washington, United States, 98104

Downtown Emergency Service Center Shelter

Seattle, Washington, United States, 98104

ROOTS Young Adult Shelter

Seattle, Washington, United States, 98105

Compass Housing Alliance Blaine Center Men's Shelter

Seattle, Washington, United States, 98109

Mary's Place North Seattle

Seattle, Washington, United States, 98133

St Martin De Porres Shelter

Seattle, Washington, United States, 98134

Compass Housing Alliance Jan & Peter's Place Women's Shelter

Seattle, Washington, United States, 98144

Mary's Place White Center

Seattle, Washington, United States, 98146

Sponsors and Collaborators

University of Washington

Genentech, Inc.

Investigators

• Principal Investigator: Helen Y Chu, MD, MPH; University of Washington

More Information

Publications:

Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC, Ishida T, Sekino H, Yamada K, Portsmouth S, Kawaguchi K, Shishido T, Arai M, Tsuchiya K, Uehara T, Watanabe A; Baloxavir Marboxil Investigators Group. Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N Engl J Med. 2018 Sep 6;379(10):913-923. doi: 10.1056/NEJMoa1716197.

Boonyaratanakornkit J, Ekici S, Magaret A, Gustafson K, Scott E, Haglund M, Kuypers J, Pergamit R, Lynch J, Chu HY. Respiratory Syncytial Virus Infection in Homeless Populations, Washington, USA. Emerg Infect Dis. 2019 Jul;25(7):1408-1411. doi: 10.3201/eid2507.181261.

Hwang SW, Orav EJ, O'Connell JJ, Lebow JM, Brennan TA. Causes of death in homeless adults in Boston. Ann Intern Med. 1997 Apr 15;126(8):625-8.

Thiberville SD, Salez N, Benkouiten S, Badiaga S, Charrel R, Brouqui P. Respiratory viruses within homeless shelters in Marseille, France. BMC Res Notes. 2014 Feb 5;7:81. doi: 10.1186/1756-0500-7-81.

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

Newman KL, Rogers JH, McCulloch D, Wilcox N, Englund JA, Boeckh M, Uyeki TM, Jackson ML, Starita L, Hughes JP, Chu HY; Seattle Flu Study Investigators. Point-of-care molecular testing and antiviral treatment of influenza in residents of homeless shelters in Seattle, WA: study protocol for a stepped-wedge cluster-randomized controlled trial. Trials. 2020 Nov 23;21(1):956. doi: 10.1186/s13063-020-04871-5.

Rogers JH, Link AC, McCulloch D, Brandstetter E, Newman KL, Jackson ML, Hughes JP, Englund JA, Boeckh M, Sugg N, Ilcisin M, Sibley TR, Fay K, Lee J, Han P, Truong M, Richardson M, Nickerson DA, Starita LM, Bedford T, Chu HY; Seattle Flu Study Investigators. Characteristics of COVID-19 in Homeless Shelters : A Community-Based Surveillance Study. Ann Intern Med. 2021 Jan;174(1):42-49. doi: 10.7326/M20-3799. Epub 2020 Sep 15.

• Responsible Party: Helen Chu, Assistant Professor, School of Medicine: Division of Allergy & Infectious Diseases, University of Washington
• ClinicalTrials.gov Identifier: NCT04141917
• Other Study ID Numbers: STUDY00007800
• First Posted: October 28, 2019
• Last Update Posted: July 20, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Plan Description

We do not currently expect to share specimens with outside investigators, but if compelling opportunities arise that will advance the overall objectives of this research, the Executive Committee of the study will consider such requests. They alone have the authority to make such decisions.

All biospecimens (nasal swabs) will be coded and identifiable through the study's main database. Any specimens shared with external investigators (if deemed appropriate by the Executive Committee) will have identifiers removed prior to sharing.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Helen Chu, University of Washington:

Tamiflu; Oseltamivir; Baloxavir; Influenza; Flu; Rapid Test; Xofluza

Additional relevant MeSH terms:

Influenza, Human; Virus Diseases; Orthomyxoviridae Infections; RNA Virus Infections; Respiratory Tract Infections; Respiratory Tract Diseases