Point of care testing for sepsis
| ISRCTN | ISRCTN97997760 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN97997760 |
| Secondary identifying numbers | 15176RMcM-SS |
- Submission date
- 22/06/2016
- Registration date
- 18/08/2016
- Last edited
- 22/06/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
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 November 2022
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
Contact information
Scientific
Kelvin Laboratory Building
The Royal Hospitals
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
| Phone | +44 2890 634140 |
|---|---|
| ronan.mcmullan@belfasttrust.hscni.net |
Public
Northern Ireland Clinical Trials Unit
1st Floor Elliott Dynes
The Royal Group of Hospitals
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
| Phone | +44 2890 63 5794 |
|---|---|
| paul.doherty@nictu.hscni.net |
Study information
| Study design | Prospective observational multi-centre cross sectional diagnostic accuracy study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Scientific title | PoinT of carE teSTing for sepsIs: a diagnosTic accuracy study |
| 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(s) | 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 |
| 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 |
| Primary outcome measure | 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 study start date | 01/05/2015 |
| Overall study end date | 30/11/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | 4501 samples |
| Total final enrolment | 3185 |
| 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 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 | 28/02/2018 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
Study participating centres
Belfast
BT12 6BA
United Kingdom
South Wharf Road
St Mary's Hospital
London
W2 1NY
United Kingdom
Birmingham Heartlands Hospital
Bordesley Green East
Birmingham
B9 5SS
United Kingdom
Wythenshawe
Manchester
M23 9LT
United Kingdom
Birmingham
B15 2TH
United Kingdom
Liverpool
L14 3LB
United Kingdom
Upper Maudlin Street
Bristol
BS2 8HW
United Kingdom
Glenshane Road
Derry
BT47 6SB
United Kingdom
Reading
RG1 5AN
United Kingdom
Poole
BH15 2JB
United Kingdom
Bretten Hall
Bush Road
Antrim
BT41 2RL
United Kingdom
London
SW10 9NH
United Kingdom
Whitechapel Road
Whitechapel
London
E1 1BB
United Kingdom
London
SE5 9RS
United Kingdom
Southampton
SO16 6YD
United Kingdom
1 Lauriston Place
Edinburgh
EH3 9YW
United Kingdom
Dundonald
Belfast
BT16 1RH
United Kingdom
Salford
M6 8HD
United Kingdom
Sponsor information
Hospital/treatment centre
Research Governance
King Edward Building
The Royal Hospitals
Grosvenor Road
Belfast
BT12 6BN
Northern Ireland
United Kingdom
"ROR" |
https://ror.org/02tdmfk69 |
|---|
Funders
Funder type
Industry
Government organisation / National government
- Alternative name(s)
- innovateuk
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/05/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Paul Doherty at NICTUTEST-IT@nictu.hscni.net |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
22/06/2022: The following changes have been made:
1. The overall trial end date was changed from 30/11/2019 to 30/11/2022
2. The intention to publish date was changed from 30/11/2020 to 30/05/2023
3. The total final recruitment was updated
4. The plain English summary has been updated to reflect these changes
19/03/2018: The overall trial end date was changed from 28/02/2018 to 30/11/2019 and the intention to publish date was changed from 28/02/2019 to 30/11/2020.
10/11/2017: The recruitment end date has been updated from 30/11/2017 to 28/02/2018. The IPD sharing statement has been added.
