Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001029987
Ethics application status
Approved
Date submitted
15/06/2020
Date registered
9/10/2020
Date last updated
22/10/2021
Date data sharing statement initially provided
9/10/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Negative predictive value of the FebriDx host response point-of-care test in patients presenting to a single Australian Emergency Department with suspected COVID-19.
Scientific title
Negative predictive value of the FebriDx host response point-of-care test in patients presenting to a single Australian Emergency Department with suspected COVID-19.
Secondary ID [1] 301512 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Respiratory Infections 317861 0
Infection 318217 0
COVID-19 318820 0
Condition category
Condition code
Respiratory 315906 315906 0 0
Other respiratory disorders / diseases
Infection 316228 316228 0 0
Other infectious diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This real-world observational diagnostic accuracy study will compare the FebriDx point of care test result to that of the COVID-19 RT-PCR reference standard with a view to determining whether FebriDx has a sufficient negative predictive value to screen suspected COVID-19 patients attending the hospital emergency department. Patients who meet the Eastern Health case definition for suspected COVID-19 infection (COVID-S) PCR testing will be invited to have same time point of care testing with the FebriDx device.

Patients who consent to participate in the trial will undergo a FebriDx finger prick test. A 5µl capillary blood sample will be taking via a built in lancet and collected into the blood collection tube which is then moved into position on the lateral flow assay component of test. This test will be performed by a healthcare professional e.g. Nurse or Doctor in the Emergency Department.

Their treating clinician will be blinded to the result, which will be directly viewed and documented by a member of the research team who is not directly involved in the patient’s clinical care. Neither the participant or the treating doctor will have access to the FebriDx result. We have done this because it is important that the result is not used as part of the management decision while we are still working out how accurate it is. A member of the research team, most likely a research nurse, will be performing the test in one of the dedicated testing areas within the department and not at the patient bedside.

All parameters will be observed retrospectively by the study team from review of electronic medical records. They key parameters being observed in patients are:
- the COVID-19 PCR result
- the FebriDx result
- presenting symptoms
- ED observations including:
- Temperature
- Respiratory rate
- Heart rate
- Blood pressure
- Oxygen saturation
- White cell count and differential on day of ED presentation (if present)
- CRP on day of ED presentation (if present)
- Influenza PCR result on day of ED presentation (if present)
- Additional subsequent viral PCR or serological results relating to relevant ED presentation (if present)
- Blood culture result on day of ED presentation (if present)
- Additional subsequent blood culture results relating to relevant ED presentation (if present)

Each participant will be observed from the point of ED triage until hospital discharge.
Intervention code [1] 317823 0
Early Detection / Screening
Comparator / control treatment
The FebriDx result will be compared to the Eastern Health Pathology COVID-19 Molecular testing reference standard.

Eastern Health does in-house real-time reverse-transcriptase Polymerase Chain Reaction (RT-PCR) qualitative detection of SARS-CoV-2, the aetiological agent for COVID-19 in individuals suspected to have the infection.

The organisation utilises oropharyngeal/(bilateral) nasal or nasopharyngeal swabs to obtain material from persons suspected to have COVID-19 infection, which is then inoculated into universal or viral transport media.
Control group
Active

Outcomes
Primary outcome [1] 324121 0
To determine the negative predictive value of FebriDx for patients presenting to an Australian Emergency Department (ED) who fit the Department of Health case definition for suspected COVID-19 (COVID-S) infection.

The FebriDx results will be compared to the COVID-19 RT-PCR based reference standard. Note: Treating physicians will be blinded to the FebriDx result - this is a biospecimen analysis study.
Timepoint [1] 324121 0
Each patient that participates in the study will have samples collected for both the COVID RT-PCR reference standard (oropharyngeal/(bilateral) nasal or nasopharyngeal swabs) and FebriDx (µl fingerstick blood sample),

The FebriDx results will be available within 10 minutes and can be interpreted for up to one hour. The FebriDx result will be directly viewed and documented by a member of the research team who is not directly involved in the patient's clinical care. The treating physician will be blinded to the FebriDx result.

At the study completion the FebriDx result will be compared to the PCR based reference standard to calculate the negative predictive value for the population in question.
Secondary outcome [1] 383816 0
To examine the correlation of the FebriDx result with alternative diagnoses in COVID-S patients who are subsequently identified as being COVID negative.
Timepoint [1] 383816 0
At the study completion patients who tested COVID-19 PCR negative, the FebriDx result will be correlation with alternative diagnoses. FebriDx can provide 3 results:
1. Viral positive, 2, Bacterial positive or 3. No Infection. The FebriDx result will be compared with the treating physician's diagnosis.
Secondary outcome [2] 386384 0
Sensitivity of the FebriDx point of care diagnostic test for COVID-19 detection will all be measured as compared to the COVID-19 RT-PCR reference standard.
Timepoint [2] 386384 0
The FebriDx results will be compared to the COVID-19 RT-PCR result at completion of the study.
Secondary outcome [3] 387173 0
The specificity of the FebriDx point of care diagnostic test for COVID-19 detection will all be measured as compared to the COVID-19 RT-PCR reference standard.
Timepoint [3] 387173 0
The FebriDx results will be compared to the COVID-19 RT-PCR result at completion of the study.
Secondary outcome [4] 387174 0
The positive predictive value of the FebriDx point of care diagnostic test for COVID-19 detection will all be measured as compared to the COVID-19 RT-PCR reference standard.
Timepoint [4] 387174 0
The FebriDx results will be compared to the COVID-19 RT-PCR result at completion of the study.

Eligibility
Key inclusion criteria
Participant inclusion criteria

Adult and paediatric patients (aged 2 and over) who meet the current Eastern Health case definition for COVID-S PCR testing at their time of ED presentation will be eligible for inclusion
Able to read an English language PICF and provide in person informed consent or consent for a minor for whom they are responsible for.

Minimum age
2 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participant exclusion criteria

- Patients having COVID-S screening testing who do not meet the Eastern Health case definition at the time of testing (eg. asymptomatic pre-operative screening, asymptomatic patients awaiting private hospital transfer).
- Patients who are critically unwell, where the treating clinician feels that testing might interfere with their immediate clinical care.
- Patients who meet any of the following FebriDx device registration exclusion criteria:
- <2 years of age
- acute respiratory symptom onset >14 days prior to testing
- current Immunosuppressive or interferon therapy
- live immunisation within the last 30 days
- fever lasting >7 days
- antibiotic or antiviral use in the preceding 14 days
- Experienced major trauma, major surgical intervention, or severe burns within the last 30 days.

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Both
Statistical methods / analysis
We propose a sample size of 300; that is, 300 administrations of the test.
This is based on the following considerations.
We assume that we shall estimate the Negative Predictive Value (NPV) directly from the sample and construct a 95% confidence interval which is one-sided (running from its lower limit up to 1). This confidence interval will be an exact interval computed using the binom.test function of the R statistical programming language. (Normal approximations are not applicable here.)
We aim for the lower limit of the 95% confidence interval to be at least 0.98. We design around a power of 80%, meaning that the probability of this happening, based on our assumptions, is 0.8.
The computation of the power was carried out by Monte Carlo simulation, because the usual approximations are not available, due to the closeness of the relevant probabilities to 1.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
8/10/2021
Actual
8/10/2021
Date of last participant enrolment
Anticipated
15/12/2022
Actual
Date of last data collection
Anticipated
31/05/2022
Actual
Sample size
Target
300
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 16903 0
Box Hill Hospital - Box Hill
Recruitment postcode(s) [1] 30556 0
3128 - Box Hill

Funding & Sponsors
Funding source category [1] 305952 0
Commercial sector/Industry
Name [1] 305952 0
Planet Innovation Pty Ltd
Country [1] 305952 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Planet Innovation
Address

436 Elgar Rd, Box Hill VIC 3128
Country
Australia
Secondary sponsor category [1] 307088 0
None
Name [1] 307088 0
Address [1] 307088 0
Country [1] 307088 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306195 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 306195 0
St Vincent's Hospital Melbourne
41 Victoria Parade, Fitzroy, VIC 3065
Ethics committee country [1] 306195 0
Australia
Date submitted for ethics approval [1] 306195 0
16/06/2020
Approval date [1] 306195 0
19/10/2020
Ethics approval number [1] 306195 0

Summary
Brief summary
During the COVID-19 pandemic of 2020, a large number of patients attending Australian Emergency Departments (EDs) require viral screening to allow appropriate disposition and treatment decision making. Over 1000 tests were performed in Box Hill ED during July 2020. This process is currently hampered by the long turnaround times of laboratory PCR testing, which currently takes up to 8 hours to be available in this setting. This prolonged COVID-19 time-to-result(s) leads to poor patient flow as COVID-19 suspected patients are held in assessment cohort areas until their results are available. Prolonged ED length of stay has been associated with adverse patient outcomes in general. In addition, lack of single occupancy rooms means that COVID-19 negative patients cohorted in these assessment areas are at risk of acquiring infection from positive patients before test results are available. Rapid, accurate diagnostic or screening tests are therefore urgently required.

Current ED testing for COVID-19 involves obtaining nasopharyngeal swabs from three sites (oropharynx and both nostrils) and performing viral PCR testing.

FebriDx (Lumos diagnostics, Sarasota, Florida, US) is a TGA registered single use point of care testing (POCT) device that detects two host response proteins, Myxovirus resistance protein A (MxA) and C reactive protein (CRP), in finger prick blood samples, and is designed to distinguish viral from bacterial respiratory infection. Results are available after 10 minutes.

A recent UK study performed by Clark et al during the pandemic, found the FebriDX test had a high accuracy for the identification of COVID-19 in hospitalised adults and suggested FebriDx could be deployed as a patient triage tool. In this study of 248 patients, the FebriDx test was shown to have a sensitivity of 93% and specificity of 86% for COVID-19 when compared to reference PCR testing. In their population this translated to a negative predictive value for COVID-19 of 93%.

Due to different testing criteria and lower population COVID-19 infection rates, Australian data is required to assess applicability of FebriDx test as a first line screening test for suspected COVID-19 patients within Australian hospitals.
Trial website
Trial related presentations / publications
Public notes
Negative predictive value of the FebriDx host response point-of-care test in patients presenting to a single Australian Emergency Department with suspected COVID-19.

Contacts
Principal investigator
Name 103046 0
Dr Paul Buntine
Address 103046 0
Eastern Health- Box Hill Hospital; 5 Arnold St Box Hill, VIC, 3128
Country 103046 0
Australia
Phone 103046 0
+61425 749 936
Fax 103046 0
Email 103046 0
[email protected]
Contact person for public queries
Name 103047 0
Mrs Shelley Westgarth-Nugent
Address 103047 0
Planet Innovation; 436 Elgar Road Box Hill VIC 3128
Country 103047 0
Australia
Phone 103047 0
+61 0412 038 213
Fax 103047 0
Email 103047 0
[email protected]
Contact person for scientific queries
Name 103048 0
Dr Paul Buntine
Address 103048 0
Eastern Health- Box Hill Hospital;5 Arnold St Box Hill, VIC, 3128
Country 103048 0
Australia
Phone 103048 0
+61 0425 749 936
Fax 103048 0
Email 103048 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Only batched, non-identifiable data will be used for sharing of study outcomes. Results will be submitted for publication in a peer reviewed journal.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseNegative predictive value of the FebriDx host response point-of-care test in patients presenting to a single Australian emergency department with suspected COVID-19: an observational diagnostic accuracy study.2022https://dx.doi.org/10.1136/bmjopen-2022-065568
N.B. These documents automatically identified may not have been verified by the study sponsor.