Tuberculosis InfectionCASTLENCT04545164
Computer Aided Screening for Tuberculosis in Low Resource Environments
A study testing CAD4TB and FujiLAM in people with Tuberculosis Infection and HIV Infections, run by London School of Hygiene and Tropical Medicine at 1 site in Malawi.
Trial summary
People living with HIV (PLHIV) who require admission to hospital in WHO Africa region have poor outcomes. TB is very common in this group, but can be difficult to diagnose. The CASTLE trial aims to determine whether systematic screening for tuberculosis using digital chest X-ray with computer-aided diagnosis… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis Infection, HIV Infections
- What is being tested?
- CAD4TB and FujiLAM
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 498 participants
- Where
- 1 siteMalawi
- Study dates
- 2 Sep 2020to 26 May 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Requires acute admission to a hospital medical ward at Zomba Central Hospital for any reason
- Is living with HIV (existing or new diagnosis, irrespective of ART status)
- Willing and able to give informed consent
Who cannot join
- Aged <18 years
- Has been admitted to a medical ward for longer than 18 hours
- Taking TB treatment before admission or has received treatment for TB within the preceding 6 months.
- Has already been in the study during an earlier hospital admission.
Trial locations and contacts
1 site in 1 country.
About this study
People living with HIV (PLHIV) who require admission to hospital in WHO Africa region have poor outcomes. TB is very common in this group, but can be difficult to diagnose.
The CASTLE trial aims to determine whether systematic screening for tuberculosis using digital chest X-ray with computer-aided diagnosis (DCXR-CAD) plus urine lipoarabinomannan testing with Fujifilm SILVAMP TB LAM (FujiLAM) plus usual care can improve admission outcomes for hospitalised PLHIV, compared to usual care alone.
Read more
Our study is a single centre, unblinded, cluster-randomised (by day of admission) trial of DCXR-CAD plus FujiLAM plus usual care vs. usual care alone for screening for TB in unselected adult PLHIV admitted to a district general hospital in Malawi.
The primary outcome is the proportion of people starting TB treatment by the time of death or hospital discharge. The secondary outcomes are all-cause mortality at 56 days from enrolment, proportion of people starting TB treatment within 24 hours from enrolment, and proportion of people with undiagnosed TB. In the CASTLE study we collect a single sputum sample for M. tb culture from participants and undiagnosed TB specifically refers to a person who did not start TB treatment by the time of death or discharge from hospital and has a M. tb cultured from their sputum sample.
Alongside the two trial arms, a third smaller diagnostic cohort arm (1 in 9 of admission days / trial clusters) will explore the range of underlying infectious pathology. The diagnostic cohort does not contribute to trial outcomes.
Read the detailed description
CASTLE is funded by Wellcome, grant reference 203905/Z/16/Z
- Conditions
- Tuberculosis Infection, HIV Infections
- Being tested
- CAD4TB, FujiLAM
- Medical subject headings
- Latent Tuberculosis, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAD4TBDiagnostic test
CAD4TB is a Computer Aided Diagnosis (CAD) image processing algorithm that can aid interpretation of Chest X-ray images to accurately detect tuberculosis.
FujiLAMDiagnostic test
Fujifilm SILVAMP TB LAM is a high sensitivity test for mycobacterial lipoarabinomannan (LAM) in urine samples.
| Study group | Role | What they receive |
|---|---|---|
| Usual Care | No intervention | Participants in the usual care arm will receive no specific trial intervention. Usual care includes tests routinely available at Zomba Central Hospital, including (but not limited to) conventional (plain film) chest X-ray, urine Alere LAM and sputum Xpert Mtb/Rif on treating clinician request. |
| DCXR-CAD and FujiLAM and usual care | Experimental | Participants randomized to the intervention arm will receive TB screening using DCXR-CAD and urine FujiLAM. The CAD score and FujLAM results will be appended into their medical notes for treating clinicians to see. If patients have a CAD score above a pre-determined threshold the study team will attempt to collect sputum for Xpert Mtb/Rif. Chest X-ray images will be available for clinicians to view. This is in addition to usual care (detailed above). Receives: Diagnostic Test: CAD4TB; Diagnostic Test: FujiLAM |
| Diagnostic cohort | Other | Patients in the observational enhanced diagnostic arm will receive an enhanced package of diagnostics. This is a smaller arm (1 in 9 of all clusters) and is observational only - participants in this arm do not contribute to trial outcomes. Receives: Diagnostic Test: CAD4TB; Diagnostic Test: FujiLAM |
What is being measured
The primary outcome is the main question the study is designed to answer.
TB treatment initiation
Proportion of participants started on TB treatment
Measured: From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)
Secondary outcomes (3)
Mortality
Time (in days) to death from any case.
Measured: Censored at 56 days from enrolment
Undiagnosed TB
Positive sputum culture for mycobacterium tuberculosis at reference lab and participant is not on TB treatment at time of hospital discharge or death.
Measured: From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)
Same day TB treatment
Proportion of people starting TB treatment within 24 hours of enrollment
Measured: 24 hours from enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2020
- Study start2 Sep 2020
- Primary completion31 Mar 2022
- Study completion26 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Tuberculosis InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 498 participants (actual)
Sponsor and investigators
- Lead sponsor
- London School of Hygiene and Tropical Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Liverpool School of Tropical Medicine, Kamuzu University of Health Sciences, Malawi-Liverpool-Wellcome Trust Clinical Research Programme
- Responsible party
- Sponsor
- Investigators
- Rachael M Burke, Principal investigator, London School of Hygiene and Tropical Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04545164
- Sponsor's protocol ID
- 17799
- Acronym
- CASTLE
- Status last verified
- May 2022
- First submitted
- 1 Sep 2020
- Last updated
- 26 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be shared on LSHTM Data Compass.
Publications
Burke RM, Nyirenda S, Twabi HH, Nliwasa M, Joekes E, Walker N, Nyirenda R, Gupta-Wright A, Fielding K, MacPherson P, Corbett EL. Design and protocol for a cluster randomised trial of enhanced diagnostics for tuberculosis screening among people living with HIV in hospital in Malawi (CASTLE study). PLoS One. 2022 Jan 10;17(1):e0261877. doi: 10.1371/journal.pone.0261877. eCollection 2022.
PubMed 35007306Burke RM, Nyirenda SK, Mtenga T, Twabi HH, Joekes E, Walker NF, Nyirenda R, Gupta-Wright A, Nliwasa M, Fielding K, MacPherson P, Corbett EL. Enhanced Tuberculosis Diagnosis With Computer-aided Chest X-ray and Urine Lipoarabinomannan in Adults With HIV Admitted to Hospital (CASTLE Study): A Cluster Randomized Trial. Clin Infect Dis. 2025 Jun 4;80(5):1143-1151. doi: 10.1093/cid/ciae273.
PubMed 38748183
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Computer Aided Screening for Tuberculosis in Low Resource Environments
- ClinicalTrials.gov ID
- NCT04545164
- Acronym / sponsor ID
- CASTLE / 17799
- Conditions
- Tuberculosis Infection, HIV Infections
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 498 participants (actual)
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Collaborators
- Liverpool School of Tropical Medicine, Kamuzu University of Health Sciences, Malawi-Liverpool-Wellcome Trust Clinical Research Programme
- Study start
- 2 Sep 2020 (actual)
- Primary completion
- 31 Mar 2022 (actual)
- Study completion
- 26 May 2022 (actual)
- First posted
- 10 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
People living with HIV (PLHIV) who require admission to hospital in WHO Africa region have poor outcomes. TB is very common in this group, but can be difficult to diagnose.
The CASTLE trial aims to determine whether systematic screening for tuberculosis using digital chest X-ray with computer-aided diagnosis (DCXR-CAD) plus urine lipoarabinomannan testing with Fujifilm SILVAMP TB LAM (FujiLAM) plus usual care can improve admission outcomes for hospitalised PLHIV, compared to usual care alone.
Our study is a single centre, unblinded, cluster-randomised (by day of admission) trial of DCXR-CAD plus FujiLAM plus usual care vs. usual care alone for screening for TB in unselected adult PLHIV admitted to a district general hospital in Malawi.
The primary outcome is the proportion of people starting TB treatment by the time of death or hospital discharge. The secondary outcomes are all-cause mortality at 56 days from enrolment, proportion of people starting TB treatment within 24 hours from enrolment, and proportion of people with undiagnosed TB. In the CASTLE study we collect a single sputum sample for M. tb culture from participants and undiagnosed TB specifically refers to a person who did not start TB treatment by the time of death or discharge from hospital and has a M. tb cultured from their sputum sample.
Alongside the two trial arms, a third smaller diagnostic cohort arm (1 in 9 of admission days / trial clusters) will explore the range of underlying infectious pathology. The diagnostic cohort does not contribute to trial outcomes.
Detailed description
CASTLE is funded by Wellcome, grant reference 203905/Z/16/Z
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Usual Care | No intervention | –Participants in the usual care arm will receive no specific trial intervention. Usual care includes tests routinely available at Zomba Central Hospital, including (but not limited to) conventional (plain film) chest X-ray, urine Alere LAM and sputum Xpert Mtb/Rif on treating clinician request. |
| DCXR-CAD and FujiLAM and usual care | Experimental | Diagnostic Test: CAD4TB, Diagnostic Test: FujiLAMParticipants randomized to the intervention arm will receive TB screening using DCXR-CAD and urine FujiLAM. The CAD score and FujLAM results will be appended into their medical notes for treating clinicians to see. If patients have a CAD score above a pre-determined threshold the study team will attempt to collect sputum for Xpert Mtb/Rif. Chest X-ray images will be available for clinicians to view. This is in addition to usual care (detailed above). |
| Diagnostic cohort | Other | Diagnostic Test: CAD4TB, Diagnostic Test: FujiLAMPatients in the observational enhanced diagnostic arm will receive an enhanced package of diagnostics. This is a smaller arm (1 in 9 of all clusters) and is observational only - participants in this arm do not contribute to trial outcomes. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Requires acute admission to a hospital medical ward at Zomba Central Hospital for any reason
- Is living with HIV (existing or new diagnosis, irrespective of ART status)
- Willing and able to give informed consent
Key exclusion criteria (4 listed)
- Aged <18 years
- Has been admitted to a medical ward for longer than 18 hours
- Taking TB treatment before admission or has received treatment for TB within the preceding 6 months.
- Has already been in the study during an earlier hospital admission.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAD4TBCAD4TB is a Computer Aided Diagnosis (CAD) image processing algorithm that can aid interpretation of Chest X-ray images to accurately detect tuberculosis. | Diagnostic test | DCXR-CAD and FujiLAM and usual care, Diagnostic cohort |
| FujiLAMFujifilm SILVAMP TB LAM is a high sensitivity test for mycobacterial lipoarabinomannan (LAM) in urine samples. | Diagnostic test | DCXR-CAD and FujiLAM and usual care, Diagnostic cohort |
Primary outcome
TB treatment initiation
Time frame: From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)
Proportion of participants started on TB treatment
3 secondary outcomes
Mortality
Time frame: Censored at 56 days from enrolment
Undiagnosed TB
Time frame: From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)
Same day TB treatment
Time frame: 24 hours from enrolment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2023.
- Background: PubMed 35007306Burke RM, Nyirenda S, Twabi HH, Nliwasa M, Joekes E, Walker N, Nyirenda R, Gupta-Wright A, Fielding K, MacPherson P, Corbett EL. Design and protocol for a cluster randomised trial of enhanced diagnostics for tuberculosis screening among people living with HIV in hospital in Malawi (CASTLE study). PLoS One. 2022 Jan 10;17(1):e0261877. doi: 10.1371/journal.pone.0261877. eCollection 2022.
- Derived from this study: PubMed 38748183Burke RM, Nyirenda SK, Mtenga T, Twabi HH, Joekes E, Walker NF, Nyirenda R, Gupta-Wright A, Nliwasa M, Fielding K, MacPherson P, Corbett EL. Enhanced Tuberculosis Diagnosis With Computer-aided Chest X-ray and Urine Lipoarabinomannan in Adults With HIV Admitted to Hospital (CASTLE Study): A Cluster Randomized Trial. Clin Infect Dis. 2025 Jun 4;80(5):1143-1151. doi: 10.1093/cid/ciae273.
- Individual participant dataSharing planned: Yes. IPD will be shared on LSHTM Data Compass.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rachael M Burke principal investigator
London School of Hygiene and Tropical Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CAD4TB and FujiLAM in people with Tuberculosis Infection and HIV Infections, run by London School of Hygiene and Tropical Medicine at 1 site in Malawi.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malawi. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TB treatment initiation (time frame: From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04545164, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2023; AzTrials last refreshed its copy on 27 Oct 2026.