300,000+ clinical trials. Find the right one.

142 active trials for Tuberculosis

Statin Adjunctive Therapy for TB (StAT- TB)

There is an urgent need for novel therapies to shorten TB treatment and improve long-term lung function outcomes. Host-directed therapies (HDT) have received significant attention recently given the ability of M. tuberculosis to subvert host immune responses and cause destructive lung pathology. Statins are among the most promising HDT agents for TB. In addition to having a highly favorable safety profile, statins have been shown to have anti-TB activity in macrophages, to synergize with anti-TB drugs, and to shorten the duration of TB treatment in the standard mouse model. The StAT-TB trial will comprise two different stages. In the 14-day Stage 1 study, investigators will test the safety and tolerability, as well as Pharmacokinetics (PK), of two different doses of pravastatin co-administered with standard anti-TB treatment. In Stage 2, investigators will test the ability of pravastatin adjunctive therapy (dose to be determined in Stage 1) to shorten the mean time to sputum culture conversion (primary endpoint) and improve lung function outcomes (secondary endpoints) relative to the standard regimen. In addition, investigators will continue to investigate the anti-TB mechanism of action of pravastatin in order to further improve HDT options for TB in the future.

Start: March 2020

Alcohol Reduction Among People With TB and HIV in India

The highest incidence of tuberculosis disease (TB) in the world is in India, accounting for 27% of all new cases globally, with approximately 86,000 among persons with HIV (PWH). Unhealthy alcohol use can worsen the health of people who have Tuberculosis (TB) and people who have both TB and HIV. Behavioral interventions that 1) target alcohol use and 2) are integrated into TB and TB/HIV care may lead to better outcomes. The goal of this study is to test if a behavioral alcohol reduction intervention integrated into TB treatment can reduce alcohol use and improve TB and HIV health outcomes among people with unhealthy alcohol use. The aims of the HATHI study are: Aim 1: To test if a 4 session behavioral alcohol reduction intervention, called CAP (Counseling on Alcohol Problems), integrated into TB and TB/HIV Care can decrease unhealthy alcohol use among persons with TB and TB and HIV. Aim 2: To test if the CAP intervention, integrated into TB and TB/HIV care can improve TB and HIV clinical outcomes; Aim 3: To evaluate barriers and facilitators to integrating CAP into TB and TB/HIV care, and to determine the incremental costs of delivering CAP in TB and HIV clinical settings. Investigators hypothesize that CAP intervention will reduce alcohol use among persons with TB and TB with HIV, and that it delivery in the TB and TB/HIV setting will be acceptable to patient and providers and feasible.

Start: January 2022

Predicting the Future: Incipient Tuberculosis

The investigators will study, prospectively, if contacts (household or close contacts) of tuberculosis (TB) patients with high C-reactive protein (CRP), low hemoglobin (Hb) levels, and a positive Xpert Host Response (HR) cartridge result develop active TB within 12 months. They will also investigate if there is a correlation between progressing to active TB within 12 months and having high levels of the iron homeostasis markers (Hepcidin, Ferritin and Transferrin). Identified index cases who agree to participate will refer their household or close contacts to also join the study. These contacts will be tested for TB and only contacts who are negative will be enrolled and followed-up at 6 months and 12 months. Blood samples will be collected at baseline and 6 months for testing. During the study period, TB testing will be done on contacts who meet symptoms criteria. At 12 months, all contacts will undergo a chest x-ray to assist in the diagnosis of TB. PreFIT will target people aged 12 to 60 years of age and both HIV negative and positive. 1515 trial participants will be recruited at Stellenbosch University in South Africa, 1515 at Fundaçao Manhiça in Mozambique and 1010 at Makerere University in Uganda, respectively.

Start: April 2021

An Open-label RCT to Evaluate a New Treatment Regimen for Patients With Multi-drug Resistant Tuberculosis

This study aims to evaluate the impact of a new injection-free six-to-nine month treatment regimen of linezolid, bedaquiline, levofloxacin, pyrazinamide (PZA) and ethionamide/high dose isoniazid (INH) compared to the conventional empiric injection-based regimen. The secondary aim is to determine if other treatment-related outcomes including adverse events, adherence to treatment, culture conversion, and cure/completion are significantly different in the intervention and conventional arms.

Start: November 2015

Xpert Active Case-finding Trial 3 (XACT-3)

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.

Start: March 2021

A Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics of TBI-223 in Healthy Adults

Partially-Blinded, Placebo-Controlled, Randomized, Single Ascending Dose (SAD) with a Food Effect Cohort to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBI-223 in Healthy Adults.

Start: January 2019

BCG Revaccination of Healthy Adolescents for the Prevention of Mycobacterium Tuberculosis Sustained Infection

The purpose of this study is to demonstrate the efficacy of Bacille Calmette Guerin (BCG) revaccination against sustained Mycobacterium tuberculosis infection versus placebo in previously BCG vaccinated QuantiFERON®-TB Gold Plus Assay (QFT) negative, healthy adolescents.

Start: October 2019

High-Dose Isoniazid Among Adult Patients With Different Genetic Variants of INH-Resistant Tuberculosis (TB)

Isoniazid (INH) is a drug commonly used to treat TB worldwide. Sometimes, the bacteria that cause TB can become resistant to INH. Resistance means that bacteria have adapted to a drug and are able to live in the presence of the drug. When TB becomes resistant to INH, INH does not work as well at fighting the bacteria. This study will treat people with INH-resistant TB with different doses of INH to see if INH can still fight the bacteria if we just increase the dose. We will compare how well the drug works at higher doses for participants who have resistant TB to how well the drug works at regular doses for participants who have TB that is not resistant. The study will also compare the safety and tolerability of the different doses of INH. Tolerability is how well people can put up with the side effects of a drug. Using increased doses of INH to treat TB that is resistant to INH is experimental and has not been approved by regulatory authorities. While there is some evidence that this approach will work, this has not yet been proven. This study will be done in two stages. Stage 1 is a pilot study to determine the feasibility of enrolling enough participants into Stage 2, the larger stage of this study. If Stage 1 is successful, then Stage 2 will begin.

Start: July 2014

Tuberculosis Infection in Women of Reproductive Age and Their Infants

Women living in low-income countries are at elevated risk of death in connection to pregnancy, as well as infants born to women in such settings. It is probable that several factors are involved, such as poverty, lack of education and access to healthcare. Infectious diseases constitute important threats to maternal health in resource-limited settings. Tuberculosis (TB) is reported to be the third leading cause of maternal death globally. Furthermore, TB can be transmitted from mother to child during pregnancy, with high risk of severe consequences for the infant. Despite these data, neither the role of TB in relation to co-existing risk factors for adverse pregnancy outcomes, nor the mechanisms involved, are well understood. It is likely that TB interacts with other characteristics, in particular socio-economic condition and HIV infection, which could obscure associations between TB and pregnancy outcomes. For this reason, it is critical to design studies so that the independent role of TB can be deduced. This project aims to investigate how TB infection in women affects the risk of adverse pregnancy outcomes in relation to co-existing factors, and how exposure to TB infection may impact growth and development of infants born to women with TB. In addition, mechanisms in which TB and the immune system during pregnancy will be explored. The project is conducted at public health facilities in Ethiopia, where 2 000 women will be recruited during antenatal care. These women will be followed until 4 years after delivery, along with their offspring born during the study period. Detailed data is collected at inclusion and at study visits during follow-up, with submission of samples for TB testing and immunological analyses. Better knowledge on the characteristics of TB infection in association with pregnancy, and how TB affects maternal and child health, can be used to construct new guidelines for management of TB in women of fertile age. This may contribute to reductions in adverse pregnancy outcomes, including maternal and infant deaths.

Start: December 2015

Addiction, HIV and Tuberculosis in Malaysian Criminal Justice Settings

The purpose of this study is to conduct empiric studies of tuberculosis (TB) among prison inmates with a history of opioid dependence. This includes: a) comprehensive TB diagnostic study (symptom screening, chest x-ray, tuberculin skin test, acid-fast bacilli smear, Gene Xpert, and sputum culture) to determine best practices for screening HIV+ and HIV- prisoners; b) A RCT of latent TB infection prevention strategies among HIV+ and HIV- prisoners with high prevalence of hepatitis C (HCV) using standard 40-week daily isoniazid (40H) vs short-course weekly isoniazid + rifapentine (12HR); and c) a 3-arm preference trial comparing post-release TB treatment completion in patients on opioid agonist treatment (methadone vs naltrexone implant) vs no opioid agonist treatment in patients being treated for active or latent TB who are transitioning to the community. Investigators will also use this data, and publicly available data to complete agent-based modeling for comparative and cost-effectiveness of various TB screening and treatment strategies among prisoners, and upon community transition post-release from prison.

Start: August 2017

Vicente Ferrer HIV Cohort Study

The VFHCS is a long-term prospective cohort study of HIV infected patients from a resource-poor rural setting in India. The aim of the study is to use data collected from routine clinical care in order to describe the epidemiology of HIV and its related conditions in the investigators area, and to study the effectiveness of health interventions in a "real-world" setting (implementation and operational research).

Start: September 2009

Early Risk Assessment in Household Contacts (?10 Years) of TB Patients by New Diagnostic Tests in 3 African Countries

The ERASE - TB study will be conducted in order to fill a critical unmet need for tuberculosis control. Persons who are in contact with an infectious TB case may become infected themselves. Among those who are infected, most will stay healthy but some will develop TB themselves. These people would benefit from preventive treatment, which would also stop TB from being spread to other persons. The problem currently is that it is impossible to determine with certainty who would require preventive treatment, and who will remain healthy. Out of 100 persons exposed to an infectious TB patient, only 2 will go on to have TB according to a study in Vietnam, but there are no good tests available to identify those with a risk for TB disease. Treating 100 persons to prevent 2 cases of TB is not effective, so preventive treatment is not used in adults and adolescents in Tanzania, Mozambique and Zimbabwe, where this study will be conducted, but also in many other settings. The ERASE - TB project will evaluate a number of newly developed diagnostic tests, to see which of those will be able to predict TB in persons at risk, and therefore steer preventive treatment well. For this, the investigators will invite 2,100 household contacts (HHC) of infectious TB patients, who are at least 10 years old, into the study. Everyone will be examined initially, and again in regular intervals, for 1.5 to 2 years; and whenever the participants will present with symptoms that could indicate that they develop TB. At every visit, the investigators will perform an X-ray and take some blood and urine samples to perform new candidate tests. At the first/baseline visit, all household contacts without TB will undergo a spirometry to evaluate their pulmonary function. If someone is unwell, the investigators will also examine sputum for the presence of TB bacilli. In the end, the investigators will then be able to say who of the persons in the study developed TB, and who remained healthy. From all samples taken at different timepoints, the investigators will then determine which test found TB early, and clearly distinguished between persons developing TB, and persons who would remain healthy .

Start: March 2021

Pulmonary Tuberculosis Sequelae in Patients With COPD

It is known that there is a complex relationship between tuberculosis and COPD. Post-tuberculosis airway disease or COPD associated with tuberculosis occurs in a significant portion of tuberculosis patients. However, it was observed that mortality rates and exacerbation rates of COPD patients with tuberculosis sequel were higher. However, the effect of tuberculosis sequela on functional outcomes in COPD patients has not been investigated in the studies. The aim of this study is to determine whether the previous tuberculosis sequelae has a functional effect on patients with COPD.

Start: May 2020

Safety and Efficacy of Various Doses and Treatment Durations of Linezolid Plus Bedaquiline and Pretomanid in Participants With Pulmonary, XDR-TB, Pre- XDR-TB or Non-responsive/Intolerant MDR-TB (ZeNix)

To evaluate the efficacy, safety and tolerability of various doses and durations of linezolid plus bedaquiline and pretomanid after 26 weeks of treatment in participants with either pulmonary XDR-TB, pre-XDR-TB, or treatment intolerant or non-responsive MDR-TB.

Start: November 2017

Aerosol BCG Challenge Study in Historically BCG-vaccinated Volunteers

The purpose of this study is to evaluate the human clinical response to BCG challenge in historically BCG-vaccinated healthy adult volunteers. It will involve 12 participants in a controlled dose escalation. Bronchoscopies will be performed 14 days post-challenge to measure BCG recovered from bronchial samples. Blood tests will be taken to look at potential immunological markers of immunity.

Start: May 2021

Investigating Immune Responses to Aerosol BCG Challenge in Healthy UK Adults

TB043 is a clinical challenge trial primarily to evaluate the safety of BCG challenge administered by the aerosol inhaled route in healthy, BCG naive UK adults. The trial will also look to evaluate and compare the amount of BCG recovered from the lungs as various points after challenge.

Start: April 2019

TB Reduction Through ART and TB Screening Project

Tuberculosis (TB) has overtaken HIV as the leading infectious cause of death worldwide and requires a major policy shift for it to be controlled in line with the WHO Stop-TB goal to "end TB". However, how to control TB at population level in the context of HIV, is unknown. Some of the best evidence to date comes from the Southern African ZAMSTAR trial, where a household-level TB /HIV intervention including TB symptom screening, HIV counselling and testing with linkage to care and isoniazid preventive therapy (IPT) as indicated, was offered to all household members of TB patients. Despite only reaching ~6% of households in the intervention communities, the data showed a nearly 20% reduction in TB disease prevalence and 50% reduction in TB infection incidence at the population-level. Increasing the scope of the intervention to all households and thus all community members, may therefore significantly change the burden of TB and "end TB". The proposed TREATS project builds on the experience of ZAMSTAR and is nested within the ongoing HPTN 071 (PopART) trial (NCT01900977), the largest ever trial of a combination HIV/TB prevention intervention being conducted in Zambia and South Africa. The project consists of 4 linked studies that will provide definitive cluster-randomised evidence of the effect of a household-level combined HIV and TB prevention intervention on the burden of TB at population level. The project will produce two major outputs of global importance to public health policy. The first will provide definitive evidence of the effectiveness of scaled up combination TB/HIV prevention interventions on TB. The second output will improve understanding of the best ways to measure the impact of public health interventions on TB burden. This is a unique opportunity to assess the impact of combination HIV prevention, including universal HIV testing and treatment, combined with population screening for active TB on the burden of TB. The HPTN071(PopART) trial,a cluster randomised trial in 21 communities in Zambia and South Africa with a population size of approximately 1 million individuals, is unlikely ever to be repeated. The recently adopted WHO guidelines of a "universal treatment" strategy for HIV, will prompt policy-makers to seek strategies of case-finding for HIV offering an opportunity to conduct TB screening on a large scale. The results from the TREATS project will therefore provide unique and timely information of the additional costs and benefits of combined TB and HIV prevention strategies at population level. TREATS will also assess novel methods to measure the effect of interventions on burden of TB in the trial communities. The latest interferon gamma release assay QuantiFERON® Gold Plus will be assessed for measuring impact of TB interventions on incidence of infection. A combination of Xpert® MTB/RIF and computer aided digital X-ray (CAD4TB) will be assessed for measuring prevalence of active TB. These new methods will provide important information about the best way of measuring TB incidence and prevalence rates and allow triangulation of the different methods to inform global estimates of TB burden in the post MDG era. The TREATS consortium will stimulate synergy between leading African research groups (Zambart, HST); new European technology (Delft Diagnostic Imaging, Qiagen); international TB bodies (The Union) and European research centres (LSHTM, Imperial College, Sheffield University and KNCV), as well as with the US funders of the HPTN071/PopART trial.

Start: June 2018

Rifampicin at High Dose for Difficult-to-Treat Tuberculosis

The purpose of this study is to assess the safety of rifampicin given at a dose three times as the standard one, in persons with tuberculosis that belong to groups that have not been widely included in previous trials.

Start: April 2021

Empirical Treatment Against Cytomegalovirus and Tuberculosis in HIV-infected Infants With Severe Pneumonia

This trial will evaluate whether empirical treatment against cytomegalovirus and tuberculosis improves survival of HIV-infected infants with severe pneumonia.

Start: March 2020

Improving TB Diagnosis and Treatment Through Basic, Applied and Health Systems Research

TB is a global health problem and in South Africa rates as the second most important problem in terms of Burden of Disease. There are many reasons for this, among which are diagnostic difficulties, extended treatments, drug resistance and health care provision. This application is concerned with all these drivers and will focus activities on a clinic which provides basic care in a very deprived socio-economic area of greater Cape Town, South Africa. Patients studied in routine, but demanding environments are our focus as these clinics are representative of many areas where TB (and HIV) are found at high prevalence. If the constraints of working in such areas can be understood and appropriate changes that work made, the investigators believe the outputs and policy changes generated in this study will contribute to future success in other settings. The investigators wish to study the implementation of the Xpert®MTB/RIF (Xpert) and Xpert Ultra (Ultra) systems in situ using a randomised controlled trial design, as opposed to a remote site (central laboratory), to assess whether time to diagnosis can be improved using point of care (POC). The investigators wish to maximise this opportunity by collecting biological samples from a patient population experiencing a TB epidemic for the evaluation of future TB diagnostics. Using human DNA, the investigators will attempt to determine reasons for poor or no treatment response. Two possibilities exist for this: a) the M. tuberculosis strain is resistant to the drug in question or b) the patient is highly susceptible to the bacterium. The investigators will determine the exome sequences of study participants with susceptible M. tuberculosis strains who show poor or no response, and compare this with rapid responders. Using 16S rRNA sequencing, the investigators will also observe how the microbiome of TB patients is altered during TB treatment and how this is associated with treatment outcome, as well as after TB treatment. This project will set the foundation for the implementation of new POC TB diagnostic technologies in clinics in South Africa. The biobanked specimens collected can be rapidly utilised for nascent technologies. Studying the patient microbiome will provide insights into what makes some patients more susceptible to TB and what microbiological changes occur during the course of anti-TB treatment.

Start: February 2018