Condition category
Infections and Infestations
Date applied
22/06/2016
Date assigned
18/08/2016
Last edited
03/10/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Sepsis is the term used to describe serious infections. Up to half of all hospitalised patients with sepsis may die. It is caused by microrganisms (microbes), such as bacteria, and one of the most important parts of treating patients with sepsis is to give them the right antibiotics as soon as possible to treat the underlying infection. Many different microbes can cause sepsis. Currently the only way to find out for sure which one to target in any particular patient is to wait for it to grow in a laboratory from a sample of their blood, or other samples (culture). As it takes at least 24-48 hours to grow in the laboratory, doctors choose 'best guess' antibiotics that can treat a lot of different microbes before they know which one would be the best fit. These are not always the right antibiotics for that particular individual, and sometimes patients only get the right treatment once there is a result from the laboratory. Randox Ltd has recently developed a new bedside device based on technology that is able to identify bacteria in patients' blood within just one hour. Looking only for characteristic fragments of over 40 different microbes means that doctors’ decisions about which treatment to give patients will not need to wait for over a day for the microbe to grow in a laboratory. This will allow treatments to be better targeted from a much earlier stage. The aim of this study is to investigate how well the new test is able to identify microbes in comparison to blood culture, which is currently the best method of measurement (gold standard).

Who can participate?
Patients aged 16 years who are admitted to ICU and are suspected of having sepsis.

What does the study involve?
Patients are screened daily by members of the clinical team and where a patient suspected of having sepsis requires a blood sample taken as part of routine clinical care; additional blood will be taken at this time and stored. At the time that the standard care blood culture is taken from a potential participant, a 5ml research sample of blood is also be collected for analysis with the new test.
An additional 10ml sample of blood is also collected on the first sampling occasion for a given patient when research staff are available at that time to process and store the sample. Each patient can contribute more than one sample to this study but there must be five days between each sample being taken.

What are the possible benefits and risks of participating?
There are no direct benefits or risks involved to the patients taking part in this study.

Where is the study run from?
At least 18 intensive care units in NHS hospitals in Northern Ireland and England (UK)

When is the study starting and how long is it expected to run for?
May 2015 to February 2018

Who is funding the study?
Innovate UK (UK)

Who is the main contact?
1. Dr Ronan McMullan (scientific)
ronan.mcmullan@belfasttrust.hscni.net
2. Mr Paul Doherty (public)
paul.doherty@nictu.hscni.net

Trial website

Contact information

Type

Scientific

Primary contact

Dr Ronan McMullan

ORCID ID

Contact details

Kelvin Laboratory Building
The Royal Hospitals
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
+44 2890 634140
ronan.mcmullan@belfasttrust.hscni.net

Type

Public

Additional contact

Mr Paul Doherty

ORCID ID

Contact details

Northern Ireland Clinical Trials Unit
1st Floor Elliott Dynes
The Royal Group of Hospitals
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
+44 2890 63 5794
paul.doherty@nictu.hscni.net

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

15176RMcM-SS

Study information

Scientific title

PoinT of carE teSTing for sepsIs: a diagnosTic accuracy study

Acronym

TEST-IT

Study hypothesis

The Randox POC Multiplex PCR test has high diagnostic accuracy, in comparison with conventional culture, for detecting pathogens in critically ill adults with suspected sepsis.

Ethics approval

1. South Central - Oxford C Research Ethics Committee, 06/07/2016, ref: 16/SC/0277
2. Scotland A REC, 07/07/2016, ref: 16/SS/0108

Study design

Prospective observational multi-centre cross sectional diagnostic accuracy study

Primary study design

Observational

Secondary study design

Cross sectional study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Condition

Sepsis

Intervention

Adult patients admitted to ICU who undergo blood culture testing for suspected sepsis are eligible for this study and will be screened daily, on the basis of the inclusion/exclusion criteria as specified in the protocol. Blood cultures will be taken in the usual manner in the course of routine care. At the time that each blood culture is taken from an eligible patient, a 5ml sample of blood will also be collected for multiplex PCR testing. An additional 10ml sample of blood will also be collected where it is the first sample or research staff are available to process and store the sample. Each patient can contribute more than one sample to this study; however an interval of at least 5-days must lapse between consecutive samples obtained.

Reference standard: Automated blood culture technology, in place as standard NHS care in microbiology laboratories at participating sites, and performed prospectively as part of usual clinical care.

Index test: Microarray-based multiplex PCR for detection of DNA from a range of at least 40 sepsis pathogens. It will be carried out using an instrument which has been developed by Randox Ltd specifically for this test. The index test will be performed retrospectively in a centralised laboratory for the first part of the study and prospectively at study sites in the latter part of the study.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Diagnostic accuracy of the multiplex PCR test, expressed as sensitivity, specificity, and positive and negative predictive values, with uncertainty expressed using 95% confidence limits.

Secondary outcome measures

1. Resource use associated with the multiplex PCR testing and conventional blood culture is measured by study-specific data collection forms at randomly generated time points over the course of the trial
2. The time required to complete testing will be measured for both Multiplex PCR and the paired blood culture. In the case of the blood culture two measures will be recorded at:
2.1. The time between sampling and the test first being reported to clinical teams as positive
2.2. The time between sampling and a final pathogen identification first being reported to clinical teams. It is acknowledged that, for both of these, the result will usually be ‘first’ reported verbally
Blood cultures that do not flag positive after 5-days of incubation will be categorised as negative with a time to result of 5-days.

Exploratory outcome measures:
1. Neutrophil activation biomarkers are measured by plasma MPO and MMP-8 in sample taken at time of reference standard
2. Plasma and serum inflammatory response biomarkers are measured by CRP, cytokines (including but not limited to TNFα, IL-1β, IL-6, IL-8), proteases and anti-proteases, activation molecule expression (including but not limited to sICAM-1), coagulation factors (including but not limited to thrombin-anti-thrombin complex, tissue factor, protein C, thrombomodulin and plasminogen activator inhibitor-1), RAGE ligands and vitamin D status
3. Pulmonary and systemic epithelial and endothelial function and injury are assessed through measuring plasma and serum biomarkers (including RAGE, Ang I/II, SP-D, vWF and PCP3) and urinary albumin/creatinine ratio in sample taken at time of reference standard
4. Surrogate markers of inflammation are measured through primary cultures fresh human neutrophils monocytes and macrophages as well as mesenchymal stromal cells in sample taken at time of reference standard

Overall trial start date

01/05/2015

Overall trial end date

28/02/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 16 years and over
2. Patients with suspected sepsis
3. Undergoing blood sampling for culture in the course of routine care

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

4501 samples

Participant exclusion criteria

1. Patients aged <16 years old
2. Patients previously recruited to the study
3. Consent declined

Recruitment start date

01/09/2016

Recruitment end date

30/11/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Belfast Health and Social Care Trust
274 Grosvenor Road
Belfast
BT12 6BA
United Kingdom

Trial participating centre

Imperial College Healthcare NHS Trust
The Bays South Wharf Road St Mary's Hospital
London
W2 1NY
United Kingdom

Trial participating centre

Heart of England NHS Foundation Trust
Bordesley House Birmingham Heartlands Hospital Bordesley Green East
Birmingham
B9 5SS
United Kingdom

Trial participating centre

University Hospital South Manchester NHS Foundation Trust
Southmoor Road Wythenshawe
Manchester
M23 9LT
United Kingdom

Trial participating centre

University Hosptials Birmingham
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Royal Liverpool and Broadgreen University Hospital
Thomas Drive
Liverpool
L14 3LB
United Kingdom

Trial participating centre

University Hospitals Bristol NHS Trust
Bristol Royal Infirmary Upper Maudlin Street
Bristol
BS2 8HW
United Kingdom

Trial participating centre

Western Health and Social Care Trust
Altnagelvin Area Hospital site Glenshane Road
Derry
BT47 6SB
United Kingdom

Trial participating centre

Royal Berkshire NHS Foundation Trust
London Road
Reading
RG1 5AN
United Kingdom

Trial participating centre

Poole Hospital NHS Foundation Trust
Longfleet Road
Poole
BH15 2JB
United Kingdom

Trial participating centre

Northern Health and Social Care Trust
Northern Health and Social Care Trust Trust Headquarters Bretten Hall Bush Road
Antrim
BT41 2RL
United Kingdom

Trial participating centre

Chelsea & Westminster Hospital NHS Foundation Trust
369 Fulham Road
London
SW10 9NH
United Kingdom

Trial participating centre

Barts Health NHS Trust
The Royal London Hospital Whitechapel Road Whitechapel
London
E1 1BB
United Kingdom

Trial participating centre

Kings College Hospital NHS Foundation Trust
Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

University Hospital Southampton NHS Trust
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Lothian Universities Hospital Trust (NHS Lothian)
Trust Headquarters 1 Lauriston Place
Edinburgh
EH3 9YW
United Kingdom

Trial participating centre

South Eastern Health and Social Care Trust
Upper Newtownards Road Dundonald
Belfast
BT16 1RH
United Kingdom

Trial participating centre

Salford Royal NHS Foundation Trust
Stott Lane
Salford
M6 8HD
United Kingdom

Sponsor information

Organisation

Belfast Health and Social Care Trust (BHSCT)

Sponsor details

Research Governance
King Edward Building
The Royal Hospitals
Grosvenor Road
Belfast
BT12 6BN
United Kingdom

Sponsor type

Government

Website

Funders

Funder type

Industry

Funder name

Innovate UK

Alternative name(s)

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

It is anticipated that the study findings will be published in national and international peer review journals which will be led by the Co-CI’s. This will secure a searchable compendium of these publications and make the results readily accessible to the public and health care professionals. In addition study findings may be presented at both national and international meetings and also to appropriate patient groups.

Intention to publish date

28/02/2019

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes