Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05845112 |
| Other study ID # |
22-084 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 2023 |
| Est. completion date |
October 2026 |
Study information
| Verified date |
April 2023 |
| Source |
Liverpool School of Tropical Medicine |
| Contact |
Ana I Cubas Atienzar, PhD |
| Phone |
01517053187 |
| Email |
ana.cubasatienzar[@]lstmed.ac.uk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Globally, tuberculosis (TB) is one of the main causes of death and the leading cause from a
single infectious agent. In 2020, an estimated 9.9 million people developed TB and 1.5
million died. Millions of people remain undiagnosed with TB, hindering efforts to end TB. TB
tests have inadequate accuracy or performance characteristics for implementation across all
populations and settings. None of the tests meet the WHO-Target-Product Profile for TB
screening and most need specialized laboratory staff and infrastructure, making them
unsuitable for primary health care (PHC).
The overall aims for this project are to:
1. Accelerate the introduction/adoption of TB diagnostic tools and test combinations at
PHC, for the timely detection of TB and improved linkage to treatment
2. Develop conditions for sustainable and equitable access to TB diagnostics tools and test
combinations within PHC,
3. Strengthen global alliances and national partnerships to enable scale-up.
The study is split into two major Phases. This application is focused on Phase 1.
Specific Phase 1 objectives are to:
4. Evaluate the performance of selected TB diagnostic tools, and
5. Identify TB test combinations that increase the proportion of people diagnosed with
bacteriologically confirmed TB.
Methods in Brief: Activities will be conducted in Bangladesh, Brazil, Kenya, Cameroon,
Malawi, Nigeria, and Vietnam.
Each country will study selected priority populations at risk of TB, including adults
attending PHC centers and district hospitals; people living with HIV (PLHIV); marginalized
populations (internally displaced, refugees and pastoralists), and children. Activities
within countries will use standardized protocols for evaluating diagnostic tests and
combinations.
Description:
Tuberculosis (TB) is second only to the coronavirus infectious disease 2019 (COVID-19) as a
single-species cause of adult infectious death worldwide1. Nearly four of the 10.6 million
people estimated to develop TB each year are not diagnosed or treated. Moreover, an estimated
1.6 million people died of TB in 2021, with the large gap between TB diagnosis and treatment
being a major contributor to mortality1-4. The World Health Organisation (WHO) has identified
30 high TB burden countries (TB burden, HIV-associated TB burden, multi-drug
resistant/rifampicin resistant-TB) that are predominately low- or low-to-middle income, and
together accounted for 86-90% of the estimated global TB incidence in 20191. Within these
countries, and globally, TB disproportionally affects the poor, and most of the 'missed'
cases occur among populations with limited access to healthcare (men, people living with HIV,
residents of rural and remote settings and informal urban settlements and displaced
populations5 and in children6.
The WHO End TB Strategy calls for a 90% reduction in TB deaths by 2030 compared to 2015, an
80% reduction in estimated TB incidence, and elimination of household catastrophic costs due
to TB. Unfortunately, the 2021 WHO Global TB Report shows that we are very far from achieving
these targets, and they will likely not be met without a step-change in efforts to improve
early diagnosis and treatment of TB. Moreover, the COVID-19 pandemic severely disrupted TB
diagnosis and treatment programs, hindering efforts to eliminate TB as a public health issue,
and the ramifications of the pandemic are likely to be experienced by fragile health systems
for many years7. New approaches to facilitate access to same-day, same-setting diagnosis and
treatment of TB are urgently required.
TB detection in adults is mainly dependent upon passive case finding (PCF), requiring
individuals to visit health facilities, be asked by health workers whether they have symptoms
consistent with TB, and subsequently tested for TB. Only some countries use active case
finding (ACF) and intensified case funding (ICF) as a complementary measure 8,9. However,
this approach has considerable limitations. Exit interviews at clinics and simulated patient
studies demonstrate that clinicians rarely ask about TB symptoms10-12, and even when patients
volunteer symptoms, sputum testing is infrequently requested, and patients are often unable
to produce sputum10. Thus, PCF is insufficient to identify most people with TB and needs to
be supplemented with other approaches, such as intensified case finding in health facilities
and ACF, which allows detection of people with infectious TB (and potentially asymptomatic
TB; an estimated 50% of prevalent community cases14), speeding up diagnosis and linkage to
treatment, and potentially reducing transmission. The location where people with presumptive
TB are tested and the timeliness of diagnosis are also important. Approaches that rely on
sputum transport networks or referral of patients to centralized laboratories often result in
diagnostic delays and poor linkage to treatment, while local testing has been associated with
increased numbers detected and confirmed and improved linkage to treatment15. TB diagnosis is
also particularly challenging for well-defined key and vulnerable populations, including:
people living in communities with very high HIV prevalence16; those living in informal urban
settlements with poor access to health facilities and marginalized communities, such as
refugees and nomadic groups; and in children.
Overall, for this study, countries have been selected to provide a broad representation from
World Bank country development groups, global regions, covering South-East Asia, Africa, and
the Americas, with a combined population of 780 million people. We have included countries
with a high TB burden in the general population (Bangladesh, Brazil, Kenya, Nigeria);
countries with a high burden of HIV-associated TB (Brazil, Cameroon, Kenya, Malawi, Nigeria);
and countries with a high burden of drug resistant TB (Bangladesh, Nigeria, Vietnam)1. Data
across partner countries, have shown that TB-affected households experienced health-related
costs reaching 50% of their annual household income in Sub Saharan African countries such as
Nigeria, Cameroon, Malawi and Kenya17-19. Given these findings, WHO's End TB Strategy
included the goal of zero TB-affected families incurring catastrophic costs. These are
defined as 20% of annual household income lost due to an episode of TB. Countries that have
conducted formal patient cost surveys employing WHO tools and definitions such as Vietnam
have measured catastrophic cost incurrence of 63% and 98% among drug susceptible (DS) DS-TB
and multidrug resistant (MDR) MDR-TB households, respectively20. Thus, as diagnostics can
play a critical role in optimizing the patient pathway, better diagnostic tools and
algorithms may also positively impact performance against the End TB Strategy's socioeconomic
indicator. In this project we will aim to demonstrate that combinations of current and newer
TB tests can facilitate TB diagnostic testing in locations where it is not currently
available; that the optimized use of tests at the point of need increases the proportion of
people correctly diagnosed, increases access to TB treatment, and potentially reduces TB
mortality and transmission.
The project will focus on key and vulnerable populations including in settings where TB
diagnostic testing is not normally performed, and people are diagnosed clinically due to
limited access to laboratory facilities. In Phase 1 we will identify new combinations of
tests to provide same-day, same-setting diagnosis, and assess the feasibility of scaling-up
and subsequent linkage to TB care that will be formally assessed in Phase 2 of the research.
