Evaluation of GeneXpert Ultra and digital chest radiography for diagnosing tuberculosis
| ISRCTN | ISRCTN77241966 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN77241966 |
- Submission date
- 03/07/2019
- Registration date
- 02/09/2019
- Last edited
- 09/09/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Tuberculosis (TB) is a major cause of morbidity and mortality worldwide and early diagnosis is key to reducing this high disease burden. The Xpert MTB/RIF assay (GeneXpert) is a rapid test for diagnosing TB which was endorsed by WHO in 2010. An improved version of the Xpert MTB/RIF, the Xpert MTB/RIF Ultra (Xpert Ultra), is now available. However, little evidence exists for the impact of Xpert Ultra on clinical outcomes among ambulatory patients in high HIV and TB burden settings. Digital radiography machines designed as portable systems with better image quality are now available. Their availability has led to renewed interest in their inclusion in the TB diagnostic pathway. The aim of this study is to find out whether the use of Xpert Ultra in HIV-positive patients attending antiretroviral (ART) clinics can increase diagnostic yield and treatment initiation, and potentially reduce the number of deaths.
Who can participate?
Patients aged 18 and over attending antiretroviral therapy (ART) clinics at Bangwe health centre and Queen Elizabeth Central Hospital (QECH) and presenting with symptoms of TB
What does the study involve?
Participants are randomly allocated to one of four groups. Participants are requested to submit two sputum samples and depending on their group, the samples are analysed with Xpert Ultra or available standard of care test (GeneXpert or microscopy). Participants are also requested to undergo chest radiography depending on their group. All participants are followed up after 28 and 56 days for TB treatment initiation and vital status.
What are the possible benefits and risks of participating?
The benefit of this study is that participants will find out whether they have TB or not and have the opportunity to start TB treatment. The study is also beneficial to healthcare providers because it will show how effective these new TB diagnostic tests are.
Where is the study run from?
1. Queen Elizabeth Central Hospital (Malawi)
2. Bangwe Health Centre (Malawi)
When is the study starting and how long is it expected to run for?
June 2018 to August 2021
Who is funding the study?
1. Helse Nord Tuberculosis Initiative
2. Foundation for Innovative New Diagnostics (FIND)
Who is the main contact?
1. Dr Marriot Nliwasa
mnliwasa@medcol.mw
2. Dr Madalo Mukoka
mmukoka@medcol.mw
Contact information
Scientific
College of Medicine
Private bag 360, Blantyre
Blantyre
Private 360
Malawi
| Phone | +265 (0)888 681 948 |
|---|---|
| mnliwasa@medcol.mw |
Public
College of Medicine
Private bag 360, Blantyre
Blantyre
Private bag 360
Malawi
| Phone | +265 (0)888 518 464 |
|---|---|
| mmukoka@medcol.mw |
Study information
| Study design | Pragmatic multi-site individually-randomized controlled trial with a 2 by 2 factorial design |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format |
| Scientific title | Utility of the Xpert® MTB/RIF Ultra assay with the GeneXpert®Omni System and digital chest radiography for diagnosis of tuberculosis in high HIV prevalence settings: protocol for a randomised control trial |
| Study acronym | FIND EXACT-TB |
| Study hypothesis | The use of Xpert Ultra in HIV-positive patients attending antiretroviral (ART) clinics can increase diagnostic yield and treatment initiation, and could potentially reduce mortality. |
| Ethics approval(s) | Approved 26/07/2019, College of Medicine Research Ethics Committee (COMREC) (College of Medicine, Private Bag 360, Blantyre, Malawi, Email: comrec@medcol.mw), ref: P.05/17/2175 |
| Condition | Tuberculosis |
| Intervention | A random allocation sequence will be generated in advance using computer-generated random numbers. This will be done by the study statistician. Randomisation will be 1:1 to the four arms of the trial and block randomised with a variable block size. Paper slips with a randomisation number will be printed and inserted and sealed in an opaque envelope. The envelopes will be kept by the study statistician and distributed consecutively to the research assistants on the enrolment of the participant. The envelope will only contain information of allocation to chest radiography. That is to say research assistants and clinicians will know if participants will have to be referred for a chest x-ray or not. As specified in each arm, chest radiography results will be offered to the responsible clinicians to help guide TB treatment. Randomisation to Xpert Ultra will only be known by the laboratory technicians (the research team and responsible clinicians will be masked to the sputum screening arm allocation). Participants will be requested to submit two sputum samples and depending on study arm, the samples will be analysed with Xpert Ultra or available standard of care test (GeneXpert or microscopy). Participants will also be requested to undergo chest radiography depending on study arm. All participants will be followed up at 28 days and 56 days for TB treatment initiation and vital status. |
| Intervention type | Other |
| Primary outcome measure | Proportion of patients initiating TB treatment within 28 days of enrolment compared between standard of care Xpert and Xpert Ultra arms |
| Secondary outcome measures | 1. Proportion of patients diagnosed with TB initiating TB treatment within 28 days of enrolment between Standard Of Care and Xpert Ultra arms 2. Time from enrolment to TB treatment initiation between Standard Of Care and Xpert Ultra arms 3. All-cause mortality risk between Standard Of Care and Xpert Ultra arms 4. Proportion of patients diagnosed with bacteriologically-confirmed TB initiating TB treatment within 28 days of enrolment between chest radiography and no chest radiography arms |
| Overall study start date | 01/06/2018 |
| Overall study end date | 01/08/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 1252 |
| Total final enrolment | 640 |
| Participant inclusion criteria | 1. Aged ≥ 18 years 2. Having TB symptoms (cough of any duration, fever, night sweats or weight loss) 3. Able to submit sputum 4. Willing and able to provide informed consent |
| Participant exclusion criteria | 1, Presence of clinical danger signs (unable to walk unaided, confused or agitated, breathless when speaking or at rest) 2. Already taking TB treatment, or taken TB treatment within the last 60 days 3. Unable to submit sputum and refuses offer of sputum induction 4. Previously been enrolled in the trial |
| Recruitment start date | 02/09/2019 |
| Recruitment end date | 31/01/2021 |
Locations
Countries of recruitment
- Malawi
Study participating centres
Blantyre
PO Box 95
Malawi
Blantyre
Private bag 66
Malawi
Sponsor information
University/education
Keppel Street
London
WC1E 7HT
England
United Kingdom
| Phone | +44 (0)20 7636 8636 |
|---|---|
| comms@lshtm.ac.uk | |
| Website | http://www.lshtm.ac.uk |
"ROR" |
https://ror.org/00a0jsq62 |
Funders
Funder type
Research organisation
No information available
No information available
Results and Publications
| Intention to publish date | 01/05/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The results of this trial will be disseminated to relevant local and international conferences. The main local conference is the annual Malawi College of Medicine research dissemination conference and the target international conference is the annual Union World Conference on Lung Health. The results of this trial will be submitted for publication in open access, medical journals. The researchers will give frequent updates to the consultants working in the medical department at the Queen Elizabeth Central Hospital. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Marriot Nliwasa (mnliwasa@medcol.mw) and Dr Madalo Mukoka- mmukoka@medcol.mw. Individual-level data will be available at the time of publishing and will be shared together with the publication. The researchers will make a GitHub repository which allows access to the datasets and allows replication of the analyses. Consent will be sought from the patients and all data will be anonymized. There are no ethical or legal restrictions. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 13/08/2022 | 09/09/2022 | Yes | No |
Editorial Notes
09/09/2022: Publication reference and total final enrolment added.
19/11/2019: The ethics approval was added.
05/09/2019: Internal review.
05/07/2019: Trial's existence confirmed by ethics committee.
