TuberculosisNCT04043390
A One-stop Shop for the Same Day Diagnosis and Management of TB and HIV
A study testing CRP and Molbio Truenat MTB, CRP and Xpert ULTRA MTB/RIF and standard test Xpert in people with Tuberculosis and Hiv, run by Liverpool School of Tropical Medicine at 1 site in Nigeria.
Trial summary
TB is a major public health problem and the second most common cause of adult death due to infection in many low-income countries. Despite major efforts to de-centralise services, accessibility to diagnosis is still limited, with one third of the 9 million cases occurring each year being missed by national control… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Hiv
- What is being tested?
- CRP and Molbio Truenat MTB, CRP and Xpert ULTRA MTB/RIF and standard test Xpert
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,100 participants
- Where
- 1 siteNigeria
- Study dates
- 21 Jan 2019to 31 Dec 2020
- 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
- Adult with presumptive TB
- At least one of the following criteria: Cough > 2-week duration, weight loss, unexplained fever, night sweats or haemoptysis.
- Willing to participate in the study
Who cannot join
- Age unknown and likely being a minor (looks <18 years old)
- Known pregnancy
- Has received or is receiving anti-TB treatment
- Already diagnosed with TB.
Trial locations and contacts
1 site in 1 country.
About this study
TB is a major public health problem and the second most common cause of adult death due to infection in many low-income countries. Despite major efforts to de-centralise services, accessibility to diagnosis is still limited, with one third of the 9 million cases occurring each year being missed by national control programmes.
New TB diagnostics suitable for use at the point-of-care are emerging. Some of these are intended for screening purposes, as an initial step to identify individuals who may have TB and should undergo further tests for confirmation. These tests may have high sensitivity, but also give false-positive results (low specificity). Other tests aim to be the confirmatory tests for TB (high specificity), but these tests are often more expensive and complex and are only available in hospital laboratories. As these tests have different purposes, it is likely they would work better in combination in a step fashion to optimise their impact and to develop an efficient diagnostic process. Furthermore, as none of the tests is versatile enough to be used in all settings, test combinations will need to consider the health system context in which they would be used. Our aim is to develop and evaluate rapid and accurate diagnostic approaches for TB that facilitate the initiation of appropriate treatment on the same day of the initial consultation in Africa.
Read more
The objectives are to
- Evaluate new diagnostics for TB (including among HIV co-infected individuals) that are suitable at the point-of-care;
- Develop diagnostic algorithms that streamline and accelerate the diagnosis of TB, allowing patients to reach clinical management decisions within a single clinic visit;
- Determine the impact of using novel point-of-care diagnostic combinations on the proportion of patients correctly initiating TB treatment within 24-48 hours of first attendance; their potential cost effectiveness
The investigators conducted studies in 2016-2018 to accomplish the first two objectives and have identified diagnostic tests that are suitable for low and middle income countries.
This document therefore refers to objective 3, which aims to
- Assess the performance of two diagnostic schemes for the diagnosis of TB when compared to culture.
- Assess the yield of two diagnostic schemes for the diagnosis of TB when compared to Xpert and
- Assess the cost of the two diagnostic schemes compared to Xpert.
Read the detailed description
The study will enrol patients in TB clinics based in 4 selected district hospitals (two in Nigeria and two in Ethiopia) and samples will be processed in a single reference laboratory. This diagnostic evaluation trial will comprise two experimental diagnostic schemes which will be compared against the standard of care:
- One experimental arm (scheme 1) will screen all patients for HIV using two rapid tests routinely used by the clinics and a rapid CRP. Selected patients will be further tested using ULTRA. Individuals with HIV will undergo an HIV VL using Xpert.
- A second experimental arm (scheme 2): will screen individuals for HIV and CRP (as in scheme 1) and selected patients will be tested using Molbio Truenat MTB. Individuals with HIV will undergo an HIV VL using Molbio Truenat HIV-VL and Truenat RIF.
- In addition, all patients will be tested using the standard of care consistent of confirmatory HIV and CRP tests, Xpert MTB/RIF and culture.
- Randomisation All patients will be randomised at a ratio of 1:1 into schemes 1 and 2. Random numbers will be generated in LSTM by a statistician independent to the study. The scheme allocations will be included in study envelopes assigned to individual study numbers. Equal number of participants will be included in Nigeria and Ethiopia.
- Proposed methods for protecting against source bias
As this is an open trial, the classification of patients will be based on objective quantitative results of laboratory tests. It is expected the test performances will vary according to HIV status. Participants will be classified according to their experimental test results
- Conditions
- Tuberculosis, Hiv
- Being tested
- CRP and Molbio Truenat MTB, CRP and Xpert ULTRA MTB/RIF, standard test Xpert, Culture as reference standard
- Keywords
- Xpert MTB/RIF, tuberculosis, diagnostics, Xpert Ultra, Truenat MTB, Truenat MTB RIF, C Reactive Protein, Xpert HIV-1 VL, Truenat HIV-1 VL, C Reactive Protein QUBE
- Medical subject headings
- Tuberculosis, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CRP and Molbio Truenat MTBDiagnostic test
Also called CRP and Truelab MTB
A molecular assay to detect M tuberculosis DNA Truenat is currently undergoing the process of endorsement by the WHO.
CRP and Xpert ULTRA MTB/RIFDiagnostic test
Also called CRP and ULTRA
A molecular assay to detect M tuberculosis DNA ULTRA is already endorsed by the WHO. However the tests are still considered experimental in Nigeria and Ethiopia.
standard test XpertDiagnostic test
The investigators will use Xpert to compare its agreement with scheme 1 (CRP plus Truenat MTB) and scheme 2 (CRP plus ULTRA).
Culture as reference standardDiagnostic test
The investigators will use culture to assess the sensitivity of schemes 1 and 2
| Study group | Role | What they receive |
|---|---|---|
| CRP and Xpert ULTRA MTB/RIF | Experimental | Scheme 1 will screen all patients for HIV using rapid tests routinely used by the clinics and a rapid CRP. Patients with CRP >10 will be further tested using Xpert ULTRA. Individuals with HIV will undergo an HIV VL using Xpert HIV-1 VL. Receives: Diagnostic Test: CRP and Xpert ULTRA MTB/RIF; Diagnostic Test: standard test Xpert; Diagnostic Test: Culture as reference standard |
| CRP and Molbio Truenat MTB | Experimental | Scheme 2 will screen individuals for HIV and CRP (as in scheme 1) and patients with CRP >10 will be tested using Molbio Truenat MTB. Individuals with HIV will undergo an HIV VL using Molbio Truenat HIV-VL and individuals with Truenat MTB-positive samples wil be tested with Truenat MTB RIF. Receives: Diagnostic Test: CRP and Molbio Truenat MTB; Diagnostic Test: standard test Xpert; Diagnostic Test: Culture as reference standard |
| standard test Xpert | No intervention | All patients receiving in scheme 1 and scheme 2 will be tested using the standard tests used in the study context. These are rapid HIV tests, Xpert MTB/RIF and culture. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Performance of two diagnostic schemes for the diagnosis of TB when compared to culture.
Sensitivity, specificity, positive and negative predictive values of schemes 1 and 2 to identify patients with TB. Culture will used as the reference standard.
Measured: "up to two months", once culture results become available
Secondary outcomes (3)
Agreement of two diagnostic schemes for the diagnosis of TB when compared to Xpert.
Assessment of the agreement between the results obtained with schemes 1 and 2 and Xpert MTB/RIF.
Xpert MTB/RIF is the recommended test for diagnosis and patients are managed according to their Xpert MTB/RIF results and clinical assessment. The investigators will describe whether the use of the schemes would result in a similar yield than the yield obtained by Xpert.
Measured: "up to two months", once culture results become available
Time required for diagnosis of the two diagnostic schemes compared to Xpert.
The investigators will describe the time required to achieve a diagnosis.
Measured: 10 months
Cost required for diagnosis of the two diagnostic schemes compared to Xpert.
The investigators will describe the costs of the tests in schemes 1 and 2 and compare these costs with the costs of screening all patients with Xpert MTB/RIF.
Measured: 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2019
- Study start21 Jan 2019
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies 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
- Model description
- This will be a phase III open randomised diagnostic trial.
- Masking
- None (open label)
- Enrolment
- 1,100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Liverpool School of Tropical Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- REACH Ethiopia, Bingham University
- Responsible party
- Sponsor
- Investigators
- Luis E Cuevas, Professor, Principal investigator, Liverpool School of Tropical Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04043390
- Sponsor's protocol ID
- 18-063
- Status last verified
- Jul 2021
- First submitted
- 19 Dec 2018
- Last updated
- 2 Aug 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data will be made open access once primary results are published and within 6 months of database lock. Data will be shared with WHO for the purpose of diagnostic endorsement.
Publications
Inbaraj LR, Daniel J, Sathya Narayanan MK, Srinivasalu VA, Bhaskar A, Scandrett K, Rajendran P, Kirubakaran R, Shewade HD, Malaisamy M, Padmapriyadarsini C, Takwoingi Y. Truenat MTB assays for pulmonary tuberculosis and rifampicin resistance in adults and adolescents. Cochrane Database Syst Rev. 2025 Mar 24;3(3):CD015543. doi: 10.1002/14651858.CD015543.pub2.
PubMed 40122135
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A One-stop Shop for the Same Day Diagnosis and Management of TB and HIV
- ClinicalTrials.gov ID
- NCT04043390
- Acronym / sponsor ID
- 18-063
- Conditions
- Tuberculosis, Hiv
- Keywords
- Xpert MTB/RIF, tuberculosis, diagnostics, Xpert Ultra, Truenat MTB, Truenat MTB RIF, C Reactive Protein, Xpert HIV-1 VL
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,100 participants (actual)
- Lead sponsor
- Liverpool School of Tropical MedicineUniversity, hospital or other
- Collaborators
- REACH Ethiopia, Bingham University
- Study start
- 21 Jan 2019 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 2 Aug 2019 (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.
TB is a major public health problem and the second most common cause of adult death due to infection in many low-income countries. Despite major efforts to de-centralise services, accessibility to diagnosis is still limited, with one third of the 9 million cases occurring each year being missed by national control programmes.
New TB diagnostics suitable for use at the point-of-care are emerging. Some of these are intended for screening purposes, as an initial step to identify individuals who may have TB and should undergo further tests for confirmation. These tests may have high sensitivity, but also give false-positive results (low specificity). Other tests aim to be the confirmatory tests for TB (high specificity), but these tests are often more expensive and complex and are only available in hospital laboratories. As these tests have different purposes, it is likely they would work better in combination in a step fashion to optimise their impact and to develop an efficient diagnostic process. Furthermore, as none of the tests is versatile enough to be used in all settings, test combinations will need to consider the health system context in which they would be used. Our aim is to develop and evaluate rapid and accurate diagnostic approaches for TB that facilitate the initiation of appropriate treatment on the same day of the initial consultation in Africa.
The objectives are to
- Evaluate new diagnostics for TB (including among HIV co-infected individuals) that are suitable at the point-of-care;
- Develop diagnostic algorithms that streamline and accelerate the diagnosis of TB, allowing patients to reach clinical management decisions within a single clinic visit;
- Determine the impact of using novel point-of-care diagnostic combinations on the proportion of patients correctly initiating TB treatment within 24-48 hours of first attendance; their potential cost effectiveness
The investigators conducted studies in 2016-2018 to accomplish the first two objectives and have identified diagnostic tests that are suitable for low and middle income countries.
This document therefore refers to objective 3, which aims to
- Assess the performance of two diagnostic schemes for the diagnosis of TB when compared to culture.
- Assess the yield of two diagnostic schemes for the diagnosis of TB when compared to Xpert and
- Assess the cost of the two diagnostic schemes compared to Xpert.
Detailed description
The study will enrol patients in TB clinics based in 4 selected district hospitals (two in Nigeria and two in Ethiopia) and samples will be processed in a single reference laboratory. This diagnostic evaluation trial will comprise two experimental diagnostic schemes which will be compared against the standard of care:
- One experimental arm (scheme 1) will screen all patients for HIV using two rapid tests routinely used by the clinics and a rapid CRP. Selected patients will be further tested using ULTRA. Individuals with HIV will undergo an HIV VL using Xpert.
- A second experimental arm (scheme 2): will screen individuals for HIV and CRP (as in scheme 1) and selected patients will be tested using Molbio Truenat MTB. Individuals with HIV will undergo an HIV VL using Molbio Truenat HIV-VL and Truenat RIF.
- In addition, all patients will be tested using the standard of care consistent of confirmatory HIV and CRP tests, Xpert MTB/RIF and culture.
- Randomisation All patients will be randomised at a ratio of 1:1 into schemes 1 and 2. Random numbers will be generated in LSTM by a statistician independent to the study. The scheme allocations will be included in study envelopes assigned to individual study numbers. Equal number of participants will be included in Nigeria and Ethiopia.
- Proposed methods for protecting against source bias
As this is an open trial, the classification of patients will be based on objective quantitative results of laboratory tests. It is expected the test performances will vary according to HIV status. Participants will be classified according to their experimental test results
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This will be a phase III open randomised diagnostic trial.
| Arm | Type | Receives |
|---|---|---|
| CRP and Xpert ULTRA MTB/RIF | Experimental | Diagnostic Test: CRP and Xpert ULTRA MTB/RIF, Diagnostic Test: standard test Xpert, Diagnostic Test: Culture as reference standardScheme 1 will screen all patients for HIV using rapid tests routinely used by the clinics and a rapid CRP. Patients with CRP >10 will be further tested using Xpert ULTRA. Individuals with HIV will undergo an HIV VL using Xpert HIV-1 VL. |
| CRP and Molbio Truenat MTB | Experimental | Diagnostic Test: CRP and Molbio Truenat MTB, Diagnostic Test: standard test Xpert, Diagnostic Test: Culture as reference standardScheme 2 will screen individuals for HIV and CRP (as in scheme 1) and patients with CRP >10 will be tested using Molbio Truenat MTB. Individuals with HIV will undergo an HIV VL using Molbio Truenat HIV-VL and individuals with Truenat MTB-positive samples wil be tested with Truenat MTB RIF. |
| standard test Xpert | No intervention | –All patients receiving in scheme 1 and scheme 2 will be tested using the standard tests used in the study context. These are rapid HIV tests, Xpert MTB/RIF and culture. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult with presumptive TB
- At least one of the following criteria: Cough > 2-week duration, weight loss, unexplained fever, night sweats or haemoptysis.
- Willing to participate in the study
Key exclusion criteria (4 listed)
- Age unknown and likely being a minor (looks <18 years old)
- Known pregnancy
- Has received or is receiving anti-TB treatment
- Already diagnosed with TB.
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 |
|---|---|---|
| CRP and Molbio Truenat MTBAlso: CRP and Truelab MTBA molecular assay to detect M tuberculosis DNA Truenat is currently undergoing the process of endorsement by the WHO. | Diagnostic test | CRP and Molbio Truenat MTB |
| CRP and Xpert ULTRA MTB/RIFAlso: CRP and ULTRAA molecular assay to detect M tuberculosis DNA ULTRA is already endorsed by the WHO. However the tests are still considered experimental in Nigeria and Ethiopia. | Diagnostic test | CRP and Xpert ULTRA MTB/RIF |
| standard test XpertThe investigators will use Xpert to compare its agreement with scheme 1 (CRP plus Truenat MTB) and scheme 2 (CRP plus ULTRA). | Diagnostic test | CRP and Molbio Truenat MTB, CRP and Xpert ULTRA MTB/RIF |
| Culture as reference standardThe investigators will use culture to assess the sensitivity of schemes 1 and 2 | Diagnostic test | CRP and Molbio Truenat MTB, CRP and Xpert ULTRA MTB/RIF |
Primary outcome
Performance of two diagnostic schemes for the diagnosis of TB when compared to culture.
Time frame: "up to two months", once culture results become available
Sensitivity, specificity, positive and negative predictive values of schemes 1 and 2 to identify patients with TB. Culture will used as the reference standard.
3 secondary outcomes
Agreement of two diagnostic schemes for the diagnosis of TB when compared to Xpert.
Time frame: "up to two months", once culture results become available
Time required for diagnosis of the two diagnostic schemes compared to Xpert.
Time frame: 10 months
Cost required for diagnosis of the two diagnostic schemes compared to Xpert.
Time frame: 10 months
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 2 Aug 2021.
- Derived from this study: PubMed 40122135Inbaraj LR, Daniel J, Sathya Narayanan MK, Srinivasalu VA, Bhaskar A, Scandrett K, Rajendran P, Kirubakaran R, Shewade HD, Malaisamy M, Padmapriyadarsini C, Takwoingi Y. Truenat MTB assays for pulmonary tuberculosis and rifampicin resistance in adults and adolescents. Cochrane Database Syst Rev. 2025 Mar 24;3(3):CD015543. doi: 10.1002/14651858.CD015543.pub2.
- Individual participant dataSharing planned: No. Data will be made open access once primary results are published and within 6 months of database lock. Data will be shared with WHO for the purpose of diagnostic endorsement.
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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.
Luis E Cuevas, Professor principal investigator
Liverpool School of 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 CRP and Molbio Truenat MTB, CRP and Xpert ULTRA MTB/RIF and standard test Xpert in people with Tuberculosis and Hiv, run by Liverpool School of Tropical Medicine at 1 site in Nigeria.
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 2 Aug 2021. 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 Nigeria. 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?
Performance of two diagnostic schemes for the diagnosis of TB when compared to culture. (time frame: "up to two months", once culture results become available). 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 NCT04043390, which also lists 1 linked publication.
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 2 Aug 2021.