Active clinical trials for "Tuberculosis"

Although curative treatment exists, tuberculosis (TB) remains the leading cause of infectious mortality worldwide - often because people seek care for TB symptoms in highly resource-constrained clinics that cannot provide same-day diagnostic testing. The research team has developed an easy-to-use clinical risk score that, if implemented in these settings, might help clinicians identify patients at high risk for TB and thereby start treatment for those patients on the same day. This study will investigate the effectiveness and implementation of this score in four peri-urban clinics in Uganda, providing critical pragmatic data to inform (or halt) the design of a definitive large-scale cluster randomized trial.

This randomized, placebo-controlled, observer-blind, safety and dose-finding Phase Ib trial will be conducted in countries in Africa, including Republic of South Africa. This trial will evaluate three dose levels of the BNT164 investigational vaccines (BNT164a1 and BNT164b1) to select a safe and tolerable dose in a three-dose schedule.

The safety, tolerability and immunogenicity of lyophilized recombinant tuberculosis vaccine (AEC/BC02) were studied in a randomized, blind, controlled phase ⅱ A clinical study in patients 18 years and older with latent infection of Mycobacterium tuberculosis.Twenty patients with negative control group and 180 patients with latent mycobacterium tuberculosis infection were divided into sentinel group, placebo group, high-dose adjuvant group, low-dose vaccine group, high-dose vaccine group and high-dose vaccine group (three doses).During the test, each subject shall not change groups or receive drugs.The negative control group did not take chemical drugs and did not get vaccinated after enrollment, and was only used as immunogenicity control.The latent infection group was given orally Koch inhibitor chemical drugs (Ifu tablet or Ifu capsule) or placebo twice a week, and then received placebo, adjuvant or vaccine every two weeks (0-2-4-6-8-10 weeks), with a total of 6 doses injected intramuscular alternately in the left and right arms of the upper arm deltoid muscle.

To compare treatment success (adherence and completion of treatment) and safety of 1HP with 3HP in HIV-uninfected adults and adolescents at increased risk of TB.

TB remains the foremost infectious disease killer globally. A startling statistic is that two out of every five TB cases globally (40%) remain undiagnosed and untreated. These 'missed' or undiagnosed cases are disproportionately concentrated in large peri-urban 'slums' and informal settlements of large cities in Africa and Asia (they are frequently minimally symptomatic but remain infectious). The lack of a sensitive low cost same-day test represented a major challenge to active community-based case finding (ACF) compared to the current model where patients 'self-seek' care (passive case finding). More recently, sensitive TB DNA-detection tests called Gene Xpert (Xpert) have become available. This is a nucleic acid amplification test-based technology which can rule-in a diagnosis of TB in two thirds of smear negative pulmonary TB cases. GeneXpert® has now been rolled out in many African countries and is the frontline TB test in primary care clinics in South Africa. The investigators recently showed that GeneXpert® significantly reduced the time to treatment initiation in the setting of passive case finding (elaborated in next section). The investigators further showed that GeneXpert® can be performed by a minimally trained healthcare worker. However, historically technical and logistical demands meant that the GeneXpert® MTB-RIF assay was not ideally suited to use at point of care and in South Africa it is still centrally located. Small portable battery-operated versions of these tests are now available (EDGE, GeneXpert two-module mobile platform). The investigators conducted a large study in South Africa and Zimbabwe (published in 2016) that showed that using the old non-portable version of Xpert on a mini-truck equipped with a generator was feasible and highly effective for ACF. A subsequent study funded by the American government (XACT II), showed that using the portable version of Xpert on the back of a small low-cost scalable panel van (in effect a mobile mini-clinic) was feasible and had a very high pick-up rate of TB in peri-urban communities (~10% of those undergoing targeted screening). In this study, the investigators will test the hypothesis that community-based active case finding (ACF) using Gene Xpert Edge (in a low cost scalable mini-mobile clinic) performed at point-of-care (POC) is feasible and more effective (lower proportion of TB cases failing to initiate treatment especially if they are 'super-spreaders' i.e. highly infectious) than Xpert performed in a centralised laboratory.

The purpose of this research is to find out if a single dose of pre-travel vaccination with BCG can lessen tuberculosis (TB) infection by producing an immune response when given to adults traveling to countries with a high burden of TB. BCG will be compared with a placebo (an inactive vaccine). BCG (Japan) is used globally but is not approved for use in the United States, therefore it is considered experimental. Participants choosing to take part in this research study, will be randomly assigned (this is like a coin flip) to BCG or placebo. 2000 eligible volunteers will be enrolled.

TB Aftermath will compare effectiveness, cost-effectiveness and feasibility of two ACF strategies for detecting recurrent TB and provide evidence needed to implement and scale the preferred ACF strategy. The specific aims are: Primary Aim 1: To conduct a non-inferiority randomized trial to measure the comparative effectiveness of two potentially implementable ACF strategies within India's National TB Elimination Program (NTEP), conducted by existing NTEP healthcare workers (HCWs): (i) home-based ACF (HACF) and (ii) telephonic ACF (TACF). Primary Aim 2: To characterize implementation processes of the ACF strategies using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to inform future scale-up and sustainability. Primary Aim 3: To model the impact and cost effectiveness of the ACF strategies evaluated in the trial, and of potential alternative strategies for the targeting and timing of those strategies. Secondary Aim: To measure the association of the severity, chronicity and progression of post-TB lung impairment with recurrent TB disease.

Tuberculosis (TB) whole genome sequencing (WGS) allows outbreak identification and disease transmission tracking. It is hypothesized that prospective WGS-guided epidemiological investigations improve case detection compared to current best practices by adapting contact tracing strategies to local transmission patterns. A cluster randomized controlled trial (cRCT) will be performed in high TB incidence villages of Haute Matsiatra region in Madagascar. Communities will be randomized in three separate TB control strategies comparing (1) standard of care, (2) the World Health Organization (WHO) recommended best practices and (3) a novel intervention involving TB WGS cluster-guided epidemiological investigations. The incremental value of TB WGS on case notifications and reduction of TB burden will be measured. Secondary studies will be nested within this cRCT will include: A qualitative study which will increase the understanding of the factors facilitating and hindering implementation of WGS-based diagnostics within health systems. A cost effectiveness analysis study which will measure the cost effectiveness of newly implemented laboratory methods. Field and genomic epidemiology data from this project will inform future work on the design of community-level TB elimination strategies in collaboration with Madagascar National TB program

A cluster randomized controlled trial to evaluate the effect of placing Truenat platform/TB assays at primary health care clinics combined with rapid communication of results on time to treatment initiation of microbiologically confirmed TB.

Diabetes mellitus (DM) increases susceptibility to Tuberculosis (TB) and worsens TB patient outcomes. The number of patients with combined TB and DM now outnumbers that of combined TB and HIV and it has been estimated that 15-30% of TB disease may be attributable to diabetes globally. This may be expected to rise substantially as DM prevalence increases. Treatment of Latent TB Infection (LTBI) in this population will likely have a significant clinical benefit. Similar to HIV-infected individuals, those with DM might benefit from therapy to prevent the development of TB disease. Current international guidelines do not recommend LTBI management in people with DM, but this is because no studies have examined the risk-benefit ratio of such an intervention. To date, no RCTs have been conducted to investigate the efficacy and safety of preventive treatment of LTBI in DM patients. Based on evidence on effectiveness, safety, and treatment completion rates, 3HP has been selected as the regimen of choice for this study of African people living with DM. People living with DM will be randomized to 3HP or placebo to determine the efficacy of 3HP in the prevention of TB disease in this population. PROTID's preventive treatment of LTBI among people with DM will generate the first solid evidence to support or refute the use of preventive treatment against TB in people with DM.