Activities
Work in TB-CAPT is structured around five activity pillars: the TB-CAPT CORE trial, the TB-CAPT XDR trial, the TB-CAPT HIV trial, Capacity building, and Dissemination.
These pillars are embedded in a robust management structure with FIND as the overall project coordinator, and LINQ supporting FIND and the whole consortium as the project management partner, safeguarding a smooth implementation.
Pillar 1 – the TB-CAPT CORE trial
Potential impact of using Truenat MTB Plus and MTB-RIF Dx assays in the most peripheral level of healthcare
Lead: Katharina Kranzer, Ludwig Maximilian University of Munich (LMU)
The Truenat™ (Molbio Diagnostics, Goa, India) testing system uses portable, battery-operated devices to rapidly detect Mycobacterium tuberculosis complex bacteria (MTBC) and rifampicin resistance. The system involves two main devices: the Trueprep® AUTO v2 Universal Cartridge based Sample Prep Device for the automated extraction and purification of DNA, and the Truelab® Real Time micro PCR Analyzer for performing real-time polymerase chain reaction (PCR), resulting in the semi-quantitative detection of MTBC. The system uses room-temperature stable reagents and Truenat™ micro PCR chips and is designed to be operated in peripheral laboratories with minimal infrastructure. In 2020 WHO reviewed performance characteristics of this molecular point-of-care test for TB and endorsed the test for TB diagnosis. Our TB-CAPT CORE trial will be a pragmatic trial to assess the impact that the Truenat MTB Plus and MTB-RIF Dx assays can have when used at the peripheral level of the health system (primary healthcare level). The trial will compare Truenat MTB assays on sputum to the current standard of care (off-site Xpert testing) and will be conducted in Tanzania and Mozambique. Overall, 28 primary healthcare level sites will enrol a total sample size of 4,200 patients.
The EDCTP funded TB-CAPT CORE trial will be complemented through co-funding of other studies (Papua New Guinea, India, Uganda, Indonesia, South Africa, Peru, Vietnam, Moldova, Brazil) to have a strong overall evidence package to support WHO policy development.
Countries involved: Mozambique, Tanzania
N° of patients: 4,200
Recruitment start: July 2022
Recruitment completion: August 2023
Clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT04568954
Pillar 2 – the TB-CAPT XDR trial
Better diagnosis and quicker initiation of treatment for patients with different types of drug resistance
Lead: Helen Cox, University of Cape Town (UCT)
In our TB-CAPT XDR trial we will implement drug sensitivity testing (DST) using the Xpert MTB/XDR cartridge and evaluate diagnostic accuracy, feasibility, and potential impact of this test in comparison to the current standards of care.
In South Africa we will be evaluating the Xpert MTB/XDR cartridge on the GeneXpert platform in a centralized laboratory setting, i.e. the existing TB diagnostics infrastructure implemented there. GeneXpert is an automated TB molecular test that was endorsed by WHO for use in TB endemic countries in 2010. It shortened the time to diagnosis from 2-6 weeks to 2 hours and can also identify resistance to rifampicin (RIF), one of the two most important anti-tuberculosis drugs.
Across all trial sites, we will evaluate samples from 753 RIF-resistant participants. With these numbers we expect to achieve high confidence in the impact of Xpert XDR on time to accurate diagnosis of patients with either isoniazid or rifampicin mono-resistance, MDR, pre-XDR or XDR patients.
Countries involved: South Africa
N° of patients: 753 RIF resistant
Recruitment start: May 2021
Recruitment completion: March 2022
Clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT04567368
Pillar 3 – the TB-CAPT HIV trial (EXULTANT)
Looking at the added value for people living with HIV
Lead: Alberto García-Basteiro, Fundación Privada Instituto de Salud Global Barcelona (ISGlobal) & Centro de Investigacao em Saude de Manhica (CISM)
Given the very high sensitivity of the Xpert Ultra assay, added value of the test will be particularly pronounced in one of the most vulnerable patient groups, hospitalized HIV+ patients. Many such patients die of TB without healthcare providers ever realizing that they have TB. The current standard of care in many countries is to only provide testing on those patients who have TB symptoms (e.g. cough) or advanced HIV disease. In PLHIV, sputum is often difficult to obtain, so symptoms themselves may be missed - switching to other more accessible samples (e.g., urine and stool) in all hospitalized PLHIV irrespective of TB symptoms could be highly beneficial. Therefore, we will assess the impact of an expanded testing strategy with Ultra for diagnosing TB amongst this important patient group. Additionally, we will assess the use of the urine-based AlereLAM assay in all hospitalized PLHIV, which also offers great potential to improve diagnosis in this particular patient population. Exploratory objectives will evaluate the utility of oral swabs, CRP and the FujiLAM assay in the diagnosis of TB.
The expanded strategy will be implemented among newly admitted unselected adult patients with HIV who are not on TB treatment, with or without symptoms suggestive of TB. We will assess the proportion of all patients enrolled with the number of bacteriologically confirmed TB started on therapy being the primary outcome and unfavourable outcomes (loss to follow-up or death at 8 weeks) as the secondary outcome in the intervention group compared to the current standard of care.
Countries involved: Mozambique and Tanzania
N° of patients: 1,172
Recruitment start: July 2022
Recruitment completion: May 2024
Clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT04568967
Pillar 4 – TB-CAPT Capacity Building
Laying the foundation for the research of the future
Lead: Klaus Reither, Swiss Tropical and Public Health Institute (SwissTPH)
TB-CAPT capacity building measures are aimed at individuals at different stages in their career path, including experienced researchers, junior scientists, as well as Master’s and PhD students that are the beginning of their career in medical research.
Following a consortium-wide needs analysis, we will prepare training content that matches the needs and interests of our African partners. Collaboration with the EDCTP-funded PANACEA and the UNITAID funded Seq&Treat projects allows us to scale this up, combining expertise and resources from all three initiatives to offer the training as a Massive Open Online Course (MOOC).
To support early-stage researchers in a tailored and individualized manner, we are setting up a mentor-mentee scheme as part of a structured support system within the TB-CAPT consortium. These measures will create and maintain support partnerships within the scientific community which will then also be sustainable beyond the project duration.
Furthermore, senior members of the TB-CAPT consortium will provide scientific guidance for Master's and PhD students, applying their expertise in the field of TB diagnostics to supporting the next generation of clinical scientists in sub-Saharan Africa.
Pillar 5 – TB-CAPT Dissemination
Making sure that results are translated into policy quickly
Lead: Marguerite Massinga, African Society for Laboratory Medicine (ASLM)
The dissemination pillar of TB-CAPT will facilitate the effective dissemination of study results to various target groups, to ensure optimal uptake and quick translation into policy. In addition, it will facilitate and support communications about the project in general.
To achieve this, we will provide evidence from clinical trials to: i) manufacturers to facilitate their product registration applications (e.g. regulatory authorities); and to ii) WHO to facilitate global policy decisions and to support the development of detailed guidelines.
Study findings will be shared and discussed with national TB programmes of our partner countries to support them in translating project results on test and process innovations into national implementation and scale-up strategies.
The African Society for Laboratory Medicine (ASLM) will play a central role in translating findings to aid scale-up beyond those countries participating in the trial, through its network of six Collaboration Centres headquartered in Senegal, Kenya, Nigeria, Ethiopia and South Africa. At the completion of the trials, ASLM will host a continent-wide forum to reach high-level policy makers and to draw attention to the importance of accelerating access to modern TB diagnosis.
Continuous general dissemination and communication will be supported by LINQ to inform patient and civil society groups as well as the public at large about the project and its progress.