Influenza Diagnosis, Treatment and Surveillance With Xpert Flu

The purpose of this study is to:

1. Evaluate the clinical performance of a newly available highly-sensitive rapid influenza test, Xpert Flu.
2. Derive and validate an adult clinical decision guideline to guide clinical testing of influenza patients who meed CDC criteria for antiviral treatment.
3. Evaluate impact of rapid influenza testing for antiviral treatment.
4. Determine cost effectiveness of influenza testing and treatment strategies.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Other: Rapid Influenza Testing with Xpert Flu

Detailed Description

Four strategically selected medical centers across the US (representing the West Coast, Southwest, Midwest; and East Coast) will enroll adult subjects presenting to the ED with an acute respiratory illness who fulfill CDC recommended criteria for receiving antiviral therapy. At each of the 4 sites, dedicated research coordinators will approach all adult (age > 18 years old) ED patients with broadly defined respiratory related complaints and screen for those who meet CDC recommended criteria for antiviral therapy (i.e. those at 'high-risk for complications' or those with 'potential influenza-related complications).

Consenting subjects will have a nasopharyngeal (NP) swab collected for both Xpert Flu testing and gold standard reverse transcription-PCR (rt-PCR) testing under a research protocol. The investigators will compare the test results from the rapid flu testing to that of the gold standard rt-PCR testing in order to assess the clinical performance characteristics of the new rapid test (Objective 1). The investigators will also collect demographics and medical historical information using a brief structured data form, which will be used in combination with rt-PCR test results to derive and validate a clinical decision guideline (Objective 2).

The investigators will simultaneously randomize 2 of the 4 hospitals to the Rapid Testing Group (which will have systematic rapid flu testing performed with results provided to the clinicians), or the Control Group (which will follow standard of care practice with testing left to the discretion of individual clinicians). This will permit comparison of rates of ED antiviral administration or prescription between the two groups to assess the clinical impact of influenza testing (Objective 3). Finally, cost data from the ED visits and subsequent hospitalization will be collected from subjects in both the rapid testing group and the control group to inform a cost-utility analysis of rapid influenza testing compared to current standard of care (Objective 4).

• Study Type: Interventional
• Enrollment (Actual): 2011
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85008
      • Maricopa Medical Center
  • California
    • Sylmar, California, United States, 91342
      • Olive View - UCLA Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Truman Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years old or older
• Acute respiratory tract infection, i.e. in the past two days the subject has experienced any of the following symptoms: new or increased cough, new or increased shortness of breath, change in sputum production (for adults 65 years or older), new sinus pain, new nasal congestion/rhinorrhea, new sore throat, new fever, triage temperature greater than or equal to 38F
• CDC Criteria for influenza antiviral treatment, i.e. is the subject at risk for influenza complications or does the subject have potential current influenza complications including: 65 years old or older, pregnant (or less than 2 weeks post-partum), American Indian or Alaska Native, morbid obesity (BMI greater than 40), current resident of a chronic care facility, chronic pulmonary disease, cardiovascular disease (except isolated hypertension), renal disease, hepatic disease, hematologic disease, metabolic disease, neurologic disease, immunosupression due to [HIV or AIDS, transplant, chemotherapy, medications, other - specify]. OR does the subject have potential current influenza complications such as: admitted to the hospital or a diagnosis of pneumonia.

Exclusion Criteria:

• Unable to speak or understand English or Spanish
• Unable to provide consent
• Lack of follow up information (i.e. working telephone number)
• Have an influenza diagnosis in the past 2 weeks (i.e. either given antivirals or had a confirmatory influenza test)
• Previously enrolled in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Arm; Participants in this arm will receive usual care (influenza testing and treatment)
Experimental: Rapid Testing; Participants in this arm will receive rapid influenza testing with Xpert Flu.	Other: Rapid Influenza Testing with Xpert Flu; Participants with recieve rapid influenza testing with Xpert Flu

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical performance of Xpert Flu	The primary outcome is the sensitivity and specificity of Cepheid Xpert Flu in detecting Influenza, as well as the positive and negative predictive value.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical decision guideline	Using rt-PCR as the gold standard for influenza testing, we will initially evaluate signs and symptoms (such as cough, fever, sore throat, shortness of breath, etc.) for their sensitivity, specificity and likelihood ratio for diagnosing influenza.	one year
Clinical Utility of Xpert Flu	Clinical utility is defined here as the proportion of high-risk subjects with confirmed influenza receiving antiviral or antiviral prescriptions in the ED in the Rapid Testing Group compared to the Control Group.	one year
Cost-effectiveness	We will perform a cost-utility analysis from the societal perspective comparing the following 4 treatment strategies: 1) treat all; 2) treat none; 3) treat based on clinical judgment; 4) treat based on Xpert Flu.	one year

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Department of Health and Human Services
• Investigators: Principal Investigator: Andrea Dugas, MD, Johns Hopkins University; Principal Investigator: Richard Rothman, MD, PhD, Johns Hopkins University

Publications and helpful links

General Publications

• Dugas AF, Hsieh YH, LoVecchio F, Moran GJ, Steele MT, Talan DA, Rothman RE; Emergency Department National Influenza Network Investigators. Derivation and Validation of a Clinical Decision Guideline for Influenza Testing in 4 US Emergency Departments. Clin Infect Dis. 2020 Jan 1;70(1):49-58. doi: 10.1093/cid/ciz171.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): June 30, 2014
• Study Completion (Actual): June 30, 2014

Study Registration Dates

• First Submitted: September 17, 2013
• First Submitted That Met QC Criteria: September 19, 2013
• First Posted (Estimate): September 20, 2013

Study Record Updates

• Last Update Posted (Actual): September 18, 2017
• Last Update Submitted That Met QC Criteria: September 15, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Influenza; antiviral treatment; diagnostic testing; rapid influenza testing
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: 6 IDSEP130014-01-01