ANZCTR - Registration

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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]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Acute Respiratory Infections

Infection

COVID-19

Condition category

Condition code

Respiratory

Other respiratory disorders / diseases

Infection

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]

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]

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]

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]

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]

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]

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]

The FebriDx results will be compared to the COVID-19 RT-PCR result at completion of the study.

Secondary outcome [3]

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]

The FebriDx results will be compared to the COVID-19 RT-PCR result at completion of the study.

Secondary outcome [4]

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]

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?

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

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Box Hill Hospital - Box Hill

Recruitment postcode(s) [1]

3128 - Box Hill

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Planet Innovation Pty Ltd

Address [1]

436 Elgar Rd, Box Hill VICTORIA 3128

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Planet Innovation

Address

436 Elgar Rd, Box Hill VIC 3128

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

St Vincent's Hospital Melbourne Human Research Ethics Committee

Ethics committee address [1]

St Vincent's Hospital Melbourne
41 Victoria Parade, Fitzroy, VIC 3065

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/06/2020

Approval date [1]

19/10/2020

Ethics approval number [1]

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

Dr Paul Buntine

Address

Eastern Health- Box Hill Hospital; 5 Arnold St Box Hill, VIC, 3128

Country

Australia

Phone

+61425 749 936

Fax

paul.buntine@easternhealth.org.au

Contact person for public queries

Name

Shelley Westgarth-Nugent

Address

Planet Innovation; 436 Elgar Road Box Hill VIC 3128

Country

Australia

Phone

+61 0412 038 213

Fax

shelley.westgarth-nugent@planetinnovation.com.au

Contact person for scientific queries

Name

Paul Buntine

Address

Eastern Health- Box Hill Hospital;5 Arnold St Box Hill, VIC, 3128

Country

Australia

Phone

+61 0425 749 936

Fax

paul.buntine@easternhealth.org.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

Source	Title	Year of Publication	DOI
Embase	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: an observational diagnostic accuracy study.	2022	https://dx.doi.org/10.1136/bmjopen-2022-065568

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically