HIV Infections, Tuberculosis Infection
Conditions
Brief 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 (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
Interventions
DIAGNOSTIC_TESTCAD4TB
CAD4TB is a Computer Aided Diagnosis (CAD) image processing algorithm that can aid interpretation of Chest X-ray images to accurately detect tuberculosis.
DIAGNOSTIC_TESTFujiLAM
Fujifilm SILVAMP TB LAM is a high sensitivity test for mycobacterial lipoarabinomannan (LAM) in urine samples.
Sponsors
Liverpool School of Tropical Medicine
Kamuzu University of Health Sciences
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
London School of Hygiene and Tropical Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TB treatment initiation | From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier) | Proportion of participants started on TB treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Same day TB treatment | 24 hours from enrolment | Proportion of people starting TB treatment within 24 hours of enrollment |
| Mortality | Censored at 56 days from enrolment | Time (in days) to death from any case. |
| Undiagnosed TB | From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier) | Positive sputum culture for mycobacterium tuberculosis at reference lab and participant is not on TB treatment at time of hospital discharge or death. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Intervention fidelity | 24 hours from enrolment | Proportion of people randomised to DCXR-CAD plus FujiLAM who have a valid CxR and CAD score recorded, and a FujiLAM result. |
| Diagnostic accuracy of DCXR-CAD | From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier) | Sensitivity, specificity, positive and negative predictor value compared to a composite microbiological gold standard. |
| Prevalence of infectious disease (enhanced diagnostic cohort) | From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier) | To describe the proportion of patients meeting a clinical or clinical / microbiological description for the following: Sepsis; Invasive bacterial disease; Cryptococcal disease; Pneumocystis jirovecci pneumonia; Bacterial pneumonia; Immune reconstitution inflammatory syndrome (IRIS); HIV treatment failure |
| Mortality (measured as a proportion) | 56 days from enrolment | Proportion of people dying by 56 days from enrolment. |
| Inpatient mortality | Censored at 56 days for those who are still alive and admitted to hospital at 56 days from enrolment. | Proportion of people dying prior to hospital discharge |
| Confirmed TB | From time of enrolment into trial to time of discharge from hospital or death (whichever is earlier) | The proportion of TB diagnoses that are microbiologically confirmed vs. clinically diagnosed without microbiological confirmation. |
Countries
Malawi
Outcome results
None listed