Clinical Research Directory

BPaLMZ for TB Meningitis

This two-stage study will compare consented research participants with tuberculous meningitis receiving experimental Bedaquiline (B), Pretomanid (Pa), Linezolid (L); Moxifloxacin (M), Pyrazinamide (Z) known as (BPaLMZ) to controls receiving SOC of rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E), known as RHZE. The experimental regimen is known as 1BPaLMZ/5PaM.

Systems Analysis and Improvement Approach to Prevent TB

This randomized trial uses the evidence-based Systems Analysis and Improvement Approach (SAIA) adapted for tuberculosis (SAIA-TB) to assess the comprehensive tuberculosis (TB) care cascade across 16 clinics in rural Eastern Cape, South Africa to improve patient outcomes. The aims of this study are to: * Evaluate the effectiveness of SAIA-TB use in clinics on TB cascade outcomes for TB patients and with high-risk contacts * Determine the drivers of SAIA-TB implementation success or failure across clinics The investigators hypothesize that SAIA-TB implementation will lead to a 20% increase in each of: TB screening, TB preventive treatment initiation, and TB disease treatment initiation during the 18-month intervention period.

Integrating Tuberculosis Treatment Into Community Pharmacies to Improve TB/HIV Outcomes in Uganda

Community pharmacies (CPs) have emerged as promising differentiated service delivery models for refilling antiretroviral therapy (ART) among people with human immunodeficiency virus (HIV). Documented benefits of CP-based refills include improved treatment adherence and viral suppression, reduced healthcare provider workload, and reduced facility congestion. This trial will evaluate the acceptability, feasibility, fidelity, and preliminary effectiveness of integrating TB treatment into CPs among people with TB/HIV in Kampala, Uganda.

Intergrated Service Delivery for Lung Health Conditions

The Advancing Lung Health in Zambia project aims to improve access to integrated screening, diagnosis, and management of tuberculosis (TB) and other priority respiratory diseases at community and primary healthcare levels. The project recognizes that many lung diseases present with similar symptoms, such as persistent cough, shortness of breath, chest pain, and difficulty breathing. Because of this overlap, focusing on a single disease can result in missed or delayed diagnoses for patients with other serious respiratory conditions. Guided by the World Health Organization's Practical Approach to Lung Health (PAL), the project promotes integrated assessment of people presenting with respiratory symptoms. The main conditions of interest include TB, post-TB lung disease (PTLD), pneumonia, silicosis, and chronic obstructive pulmonary disease (COPD). This approach ensures that patients receive comprehensive evaluation and appropriate care regardless of the underlying cause of their symptoms. A key feature of the project is the use of AI-enabled digital chest X-ray technology to support early and accurate detection of lung abnormalities. The technology assists healthcare workers in identifying signs of TB and other respiratory diseases, improving clinical decision-making and timely referral for further diagnosis and treatment. The project also strengthens healthcare worker capacity, expands access to diagnostic services, enhances community awareness, and improves referral and follow-up systems. In addition, it seeks to generate evidence on the burden and patterns of non-TB respiratory diseases in Zambia while documenting good practices and lessons learned from integrated lung health screening. The evidence generated will help inform policy, strengthen primary healthcare services, and support the scale-up of integrated lung health approaches, ultimately improving respiratory health outcomes and access to quality care across Zambia.

KAP TB in Senior Management Officials of Companies With Increased Silica Exposure

The study was designed as a descriptive cross-sectional survey conducted between February and October 2022. Senior management officials were targeted because of their role in workplace policy and oversight. The sample was drawn from companies registered under the Zambia Chamber of Commerce and Industry (ZACCI), focusing on those with known silica dust exposure. Each company was asked to provide one or two senior officials to participate. A total of 118 individuals completed the survey. Data collection was carried out using a self-administered electronic questionnaire developed in line with WHO recommendations for TB KAP surveys. The questionnaire contained 28 mandatory closed-ended questions: 7 on knowledge, 8 on attitudes, and 13 on practices (with 5 practice questions excluded from scoring as they were programmatic). Responses were validated by three medical doctors, and scoring was based on correct answers. Knowledge, attitude, and practice scores were categorized into "poor" or "good" using mean or median cutoffs depending on distribution. Logistic regression was applied to explore associations between participant characteristics and KAP outcomes.

COPD-PTB Screening Trial in Henan, China

The goal of this trial is to evaluate the effectiveness of an active case-finding (ACF) strategy for detecting pulmonary tuberculosis (PTB) among patients with chronic obstructive pulmonary disease (COPD) in primary care settings in Henan Province, China. It will also assess the epidemiological status of COPD-PTB comorbidity in this population and evaluate the feasibility of the ACF strategy in real-world primary care settings. This is a stepped-wedge cluster randomized controlled trial. Specifically, the intervention group will receive the ACF strategy in Year 1, Year 2, and Year 3, while the control group will receive routine follow-up care in Year 1 and Year 2, and will transition to receive the ACF intervention in Year 3. All clusters will eventually receive the ACF intervention. The main questions it aims to answer are: Does the ACF strategy decrease the prevalence of PTB among COPD patients compared with routine passive case-finding? What are the current prevalence and epidemiological characteristics of COPD-PTB comorbidity in primary care settings in Henan Province? Participants will: Receive ACF screening during their routine COPD follow-up visits in the intervention phase. Continue their usual COPD care as prescribed by their healthcare providers. If diagnosed with PTB through ACF screening, participants will be referred to designated hospitals for treatment in accordance with the national standardized tuberculosis treatment protocol.

Comparative Trial Between Ainuovirine(ANV)/Lamivudine(3TC)/Tenofovir(TDF) and Efavirenz(EFV)/Lamivudine/Tenofovir Regimens

This is a prospective, multicenter, open-label, parallel-controlled study. The primary objective is to prospectively explore and compare the virological efficacy of Ainuovirine/Lamivudine/Tenofovir and Efavirenz/Lamivudine/Tenofovir regimens combined with rifampicin and isoniazid-based anti-tuberculosis therapy in HIV-infected patients with active tuberculosis. Participants are divided into two groups to compare the virological suppression rate and immunological efficacy between the two antiretroviral regimens. All subjects will receive continuous antiretroviral medication and anti-tuberculosis drugs under medical supervision throughout the study.

Pre- and Post-treatment Lung Microbiota, Metabolome and Immune Signatures at the Site of Disease in Patients With Active Pulmonary Tuberculosis

The diverse microbial communities in different parts of the human body (microbiome) are important for health but understudied in pulmonary tuberculosis (TB), which is the single biggest infectious cause of death in the world. The investigators will study the site-of-disease microbiome (in the lung bronchoalveolar space) in TB cases to investigate how, before TB treatment, metabolic compounds made by microbes affect host biomarkers important for TB control. The investigators will ask this question again at the end-of-treatment and one year later. Specifically, the investigators will sample the lung at the active TB hotspot identified by imaging and compare this to a non-involved lung segment usually in the opposite lung. The investigators will compare the lung microbiome to other sites in the body (i.e. oral cavity, nasopharynx, supraglottis, and gut). A small amount of blood (\~15 ml) will be collected to assess peripheral immunological correlates of the host microbiome. Protected specimen brushings of the lung will be used to explore transcriptomic signatures and how these relate to the lung microbiome. The investigators will also apply these questions to the same number of controls (healthy patients and patients with an alternative diagnoses). This will lay the foundation for clinical trials to evaluate if specific bacteria have diagnostic (e.g., PCR) or therapeutic potential (e.g., antibiotics, prebiotics, probiotics, vaccines) where targeting the microbiome could improve clinical outcomes.

Start4All SCREEN-TB PROTOCOL

Tuberculosis (TB) remains the leading cause of death from a single infectious agent globally, with millions of people still undiagnosed or diagnosed late. Conventional case-finding strategies rely heavily on symptom screening using the WHO Four-Symptom Screen ((W4SS; comprising any one of current cough, fever, night sweats, or weight loss) and sputum testing, but these approaches miss a substantial proportion of individuals with active TB disease, particularly those who are asymptomatic or unable to produce sputum. Missed and delayed diagnoses drive ongoing transmission and undermine global TB elimination goals. Recent evidence has shown that diagnostic tools which are more accessible, even if somewhat less sensitive, can still substantially improve TB case detection by reducing diagnostic loss associated with access barriers. This suggests that near point-of-care (NPOC) tests might be highly cost-effective in many settings, because the gains from earlier diagnosis, reduced delays, and broader reach could outweigh losses from slightly lower accuracy. The purpose of this study is to evaluate new, symptom-agnostic screening and diagnostic approaches that can be implemented at lower-level health facilities in high TB-burden, low and middle-income (LMIC) countries for adults ≥15 years and 10-14 years old young adolescents

Parent Study Name: Pulmonary Rehabilitation to Reduce Post-Tuberculosis Morbidity (TB Pure)

Individual-level, unblinded randomized controlled trial of an 8-week (short arm) or 24-week (extended arm) pulmonary rehabilitation program, relative to standard of care, to prevent post-tuberculosis respiratory morbidity. Randomization will occur in a 1:1:1 ratio at the initiation of treatment.

Start4All - Start Taking Action for TB Diagnosis (DARE-TB)

DARE-TB has been designed to address critical evidence gaps on the diagnostic performance and operational value of near point-of-care (NPOC) nucleic acid amplification tests (NAATs) within community-based case finding (CBCF) strategies. Although World Health Organization (WHO) recommends wider access to molecular testing, its use remains concentrated in facility-based settings well short of the global targets and largely dependent on sputum production. This creates a substantial diagnostic gap for people reached through community screening who either cannot provide sputum or whose sputum specimens cannot be tested on a NAAT at a facility, particularly for marginalized, hard-to-reach populations with poor access to healthcare.

Start Taking Action for Tuberculosis in Kids

Start4Kids: Evaluating the performance, feasibility, acceptability and cost effectiveness of computer-aided detection (CAD) of chest X-ray (CXR) and concurrent testing using novel diagnostics and non-sputum specimens for childhood tuberculosis (TB) in Bangladesh, Cameroon, Kenya and Viet Nam.

Introduction of Dispersible 3HP Formulations for TB Preventive Treatment in Children: a Multi-country Evaluation

The WHO has recommended TB preventive therapy (TPT) for children living with HIV (CLHIV) and household contacts of people living with TB, however, the scale-up and implementation of TPT has been sub-optimal globally particularly in children. A safe and effective short-course TPT regimen, 3HP (rifapentine and isoniazid given once weekly for three months), is available but there is a lack of child-friendly formulations resulting in increased pill burden and there is a need to improve acceptability and adherence among children. The introduction of a dispersible rifapentine formulation has potential to improve uptake, treatment adherence and completion. Overall goal is to generate critical knowledge to improve delivery of TPT and, more specifically, of dispersible 3HP, in children in routine programs. This evaluation will create an important understanding of TPT uptake and completion among children and assess the impact of the introduction of a dispersible 3HP formulation. These results will provide actionable information for improving service delivery and the scale-up of TPT in the respective countries.