Evaluating the performance of blood-based test (Actiphage test) for active tuberculosis
| ISRCTN | ISRCTN18158855 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18158855 |
| IRAS number | 328778 |
| Secondary identifying numbers | IRAS 328778, CPMS 56391 |
- Submission date
- 07/07/2023
- Registration date
- 11/07/2023
- Last edited
- 03/01/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
Tuberculosis (TB) remains a significant global health concern, leading to severe illness and mortality worldwide. The current diagnosis of TB relies on patients producing sputum and culturing bacteria from the sputum, a process that can take several days to weeks, resulting in delayed diagnosis. Moreover, some individuals are unable to produce sputum, necessitating invasive procedures such as bronchoscopy. In order to combat TB effectively, improved diagnostic tests are required to enable rapid detection and treatment.
The objective of this study is to evaluate the performance of a potential novel blood test for TB called the Actiphage test. Developed by PBD Biotech Ltd, the Actiphage test aims to detect the bacteria responsible for causing TB directly from the blood. This study seeks to generate additional data to assess the practical effectiveness of the Actiphage test. To achieve this, two distinct groups of participants will be included: those diagnosed with TB and individuals who are unwell but do not have TB.
A total of 103 participants will be recruited for this observational study, which will be conducted over a period of 12 months at the University Hospitals of Leicester NHS Trust, serving as the sole research center.
Who can participate?
People with suspected or confirmed pneumonia or tuberculosis presenting to University Hospitals of Leicester NHS Trust.
What does the study involve?
This study requires blood to be taken at a single visit. If you agree to take part, we will collect up to 30mls of blood (6 teaspoons) for the research at the time you are having blood taken as part of your clinical investigation. This will avoid the need for you to have additional venepuncture (needle inserted to collect blood). It will take no longer than 10 minutes to collect this additional blood volume. In addition to this, we will collect other clinical and demographic data recorded during your clinical assessment (such as your age, gender, ethnicity, diagnosis and other clinical data collected as part of your normal clinical care.) The visit should not exceed 1 hour.
Your participation in the study will end after one visit. In the unlikely event that a problem arises with the shipment or processing of the blood sample, we may ask you to provide a further 7.5 ml (1.5 teaspoons) blood sample at your next scheduled clinical visit.
What are the possible benefits and risks of participating?
It is unlikely that this study will directly help you but the information we get from this study may help people with TB in the future.
There are minimal risks associated with study procedures. When research blood samples are taken there may be minor discomfort at the site where the needle is inserted. All blood samples will be taken by a doctor or fully trained health professional at the same time as your routine blood samples, to ensure no further venepuncture is required.
Where is the study run from?
University of Leicester (UK)
When is the study starting and how long is it expected to run for?
May 2023 to October 2024
Who is funding the study?
The study is being funded by the company that have developed the test (PBD Biotech Ltd). This study is sponsored by the University of Leicester. It is supported by the NIHR Leicester Biomedical Research Centre - Respiratory & Infection (Glenfield Hospital) (UK).
Who is the main contact?
Dr P Haldar, ph62@leicester.ac.uk
Contact information
Principal Investigator
NIHR Respiratory Biomedical Research Centre
Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom
 ORCID ID |
0000-0002-1572-5421 |
|---|---|
| Phone | +44 1162583370 |
| ph62@leicester.ac.uk |
Study information
| Study design | Single-centre observational cross-sectional cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Evaluating the diagnostic utility of Actiphage® for active pulmonary TB in a low burden setting |
| Study acronym | PHAGE-TB |
| Study objectives | Active tuberculosis (TB) disease is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that affects more than 10 million people globally each year. The microbiological diagnosis of pulmonary TB relies on patient producing sputum and culturing bacteria from sputum. For patients who do not produce sputum, invasive sampling with bronchoscopy may be required for microbiological diagnosis. Culturing bacteria takes days to weeks, resulting in delay in diagnosis and treatment. Actiphage is a blood-based assay which can detect viable Mtb in circulation. The assay is potentially advantageous as it is performed on blood which is universally accessible and provides a result within hours. The study will build on observations reported in a recent, small proof of concept single-centre study (Leicester) that demonstrated Actiphage based detection of Mtb in the blood of treatment naive pulmonary TB patients, with a sensitivity of 73% and specificity of 100%. In that study, sensitivity of the assay associated with radiological and microbiological correlates of increased disease severity. The present study aims to extend these observations to provide supporting evidence for validation in an independent fully characterised cohort at Leicester (UK). This study will gather evidence to determine the utility of the Actiphage assay as a blood-based TB diagnostic. |
| Ethics approval(s) |
Approved 03/07/2023, South Central – Hampshire A (Health Research Authority, 2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 207 104 8388; hampshirea.rec@hra.nhs.uk), ref: 23/SC/0222 |
| Health condition(s) or problem(s) studied | Diagnosis of active tuberculosis disease |
| Intervention | This will be an observational cohort study, recruiting patients who present to hospital with suspected active TB or acute pneumonia (control group). Consenting participants will have blood collected for research at the time of clinical blood sampling to avoid additional venepuncture. Up to 30mls of blood will be collected for research tests at a single time point and will include: i. two aliquots of blood for Actiphage testing; ii. one aliquot for interferon gamma release assay (IGRA) testing using QuantiFERON-TB Gold Plus (QFT); iii. and one aliquot for Mtb blood culture. The consent and research visit will take place during the hospital stay for hospitalised patients. Clinical investigations for TB will be in accordance with routine practice and include venous blood sampling (complete blood count, biochemistry, CRP, HIV serology and IGRA); respiratory sample microbiological testing (Xpert MTB/RIF Ultra, routine and mycobacterial culture) for expectorated samples; and chest X-ray. Demographic and clinical data will be systematically recorded on the study case report form. The outcome of Actiphage testing will not be considered in the diagnosis of active TB. The study will neither interfere with, nor influence the routine clinical management and journey of the patient. |
| Intervention type | Other |
| Primary outcome measure | Actiphage test for diagnosis of TB at a single time point. Diagnosis of TB is made according to standard clinical criteria based on microbiological, histological, and radiological evidence that is collected by reviewing patient medial notes. Actiphage test will be performed according to the manufacturer’s instructions. |
| Secondary outcome measures | Agreement between Actiphage test results for contemporaneous samples tested at PBD laboratories and Leicester. Actiphage test will be performed according to the manufacturer’s instructions. |
| Overall study start date | 05/05/2023 |
| Completion date | 30/10/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Other |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | 103 |
| Key inclusion criteria | 1. Able to give informed consent to participate in the study 2. Aged 16 years or above, presenting with suspected pulmonary TB or acute community acquired pneumonia (CAP) and managed by Adult Services at University Hospitals of Leicester NHS Trust (UHL) 3. Recruitment of CAP patients will be selective and focus on: 3.1. Patients with a CXR that is coded for TB or mentions TB as a possibility in the report; AND / OR 3.2. Demographic matching (age and ethnicity) with recruited pulmonary TB cohort; AND / OR iii. patients with a clinical history of any red flag TB symptoms exceeding 2 weeks (cough, fever, night sweats, weight loss) persisting symptoms after a course of oral antibiotics |
| Key exclusion criteria | 1. Treated with anti-tuberculous medication at any time in previous 12 months 2. Participation in an interventional clinical study in the 3 months prior to Visit 1 or participation in a study using interventional medicinal products in the previous 6 months |
| Date of first enrolment | 17/07/2023 |
| Date of final enrolment | 31/07/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Leicester
LE3 9QP
United Kingdom
Sponsor information
University/education
Research Governance Office, Research and Enterprise Division
University of Leicester
Leicester General Hospital
Leicester
LE5 4PW
England
United Kingdom
| Phone | +44 116 258 4393 |
|---|---|
| rgosponsor@le.ac.uk | |
| Website | http://www.le.ac.uk/ |
"ROR" |
https://ror.org/04h699437 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 31/10/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a peer-reviewed scientific journal. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from Dr Pranabashis Haldar (email: ph62@leicester.ac.uk) |
Editorial Notes
03/01/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 31/01/2024 to 31/07/2024.
2. The overall study end date was changed from 30/07/2024 to 30/10/2024.
3. The intention to publish date was changed from 31/07/2025 to 31/10/2025.
08/08/2023: Internal review.
11/07/2023: Trial's existence confirmed by South Central – Hampshire A REC.
