Test-and-treat for Influenza in Homeless Shelters

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Influenza, Respiratory Viral Infection

Intervention / Treatment
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* Combination Product: Point-of-care molecular testing and treatment of influenza


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard influenza surveillance<br>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<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Cases of Influenza in Shelters During the Intervention Period Compared to the Control Period | The intervention period is when test and treatment on-site was available and the control period is when just standard surveillance was available at a shelter. | Year 1 of the intervention (4.5 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Implementation of Point-of-care Molecular Testing and Treatment of Influenza in Shelters | Number of participants/participant encounters with les than 48 hours between symptom onset until diagnosis with RT-PCR. | Up to 24 months | 
| Feasibility of Implementation of Influenza Treatment in Shelters | Number of influenza-positive participants identified through on-site molecular testing in the intervention period that were treated with an antiviral | Up to 24 months | 
| Number of Participants That Drop Out of Study | Measured as becoming lost to follow-up (did not complete both follow-up study visits on day 2/3 and day 5/6/7) after testing positive for influenza at baseline enrollment with an on-site molecular test and receiving an antiviral | Up to 24 months | 
| Number of Participants That Show Non-compliance With Study Drug | 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. Non-compliance is measured as the participant self-reporting fewer doses taken than to be expected at time of of follow-up (e.g. a participant that took there first dose of oseltamivir in the AM on March 8 would be expected to have taken 6 doses if their follow-up visit was in the PM on March 10). | Up to 24 months | 
| Number of Laboratory-confirmed Influenza Cases That Report Fever | Based on self-report of new or worsening fever in the past 7 days; not gold standard measurement | Up to 24 months | 
| Influenza Viral RNA Levels | Measured mean cycle threshold (Ct) value for each laboratory-confirmed influenza-positive specimen collected at baseline enrollment, by subtype. Ct values have an inverse relationship with viral load. | Up to 24 months | 
| Number of Samples With Detectable Influenza RNA Virus at Days 2/3 and Days 5/6/7 | Measured at subject follow-up visits with nasal swabs provided to study staff; provided subject has not become lost to follow up. | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tamiflu, Oseltamivir, Baloxavir, Influenza, Flu, Rapid Test, Xofluza