View clinical trials related to Tuberculosis.
Filter by:HIV/Tuberculosis (TB) co-infection have profound effects on the host's immune system. TB is the most common cause of death in patients with HIV worldwide. Rifamycins (such as rifampicin [RIF]) are an important component of TB therapy because of their unique activity. The problem is that most protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) used to treat HIV have significant drug-drug interactions with RIF that can lead to reduced concentrations of these agents with risk of treatment failure or resistance. The non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) does not present the same significant drug interactions with RIF. EFV-based HIV treatment was tested in patients concomitantly treated with RIF-containing TB therapy, demonstrating that their co-administration can be used safely and effectively. However, the side effect profile of EFV overlaps with the RIF-containing TB regimens and makes the management of treatment toxicities very complex. Integrase inhibitors (INI), such as dolutegravir (DTG), may offer an important alternative to EFV-based therapy in TB coinfected patients. A Phase I drug-drug interaction study was conducted in healthy, HIV-seronegative subjects, and showed that DTG at 50 mg twice daily given together with RIF was well-tolerated and resulted in DTG concentrations similar to those of DTG 50 mg given once daily alone, which is the recommended dose for INI-naive patients. Therefore, ART regimens using DTG 50 mg twice daily may represent a new treatment option for TB-infected patients who require concurrent treatment for HIV infection. This is a Phase III b, randomized, open-label study describing the efficacy and safety of DTG and EFV-containing ART regimens in HIV/TB co-infected patients. This study is designed to assess the antiviral activity of DTG or efavirenz (EFV) ART-containing regimens through 48 weeks. A total of approximately 115 +/-5% subjects will be randomly assigned in a 3:2 ratio to DTG (approximately 69 subjects) and EFV (approximately 46 subjects), respectively. This study will include a Screening Period, a Randomized Phase (Day 1 to 48 weeks plus a 4-week extension), and a DTG Open-label extension (OLE). During the DTG OLE, subjects will be supplied with DTG until it is locally approved and commercially available, the subject no longer derives clinical benefit, or the subject meets a protocol-defined reason for discontinuation, which ever comes first.
Background: The disease burden of tuberculosis (TB), second only to HIV/AIDS among infectious diseases, is a major public health problem in developing countries. Accumulating evidence suggests that iron status is a primary determinant of TB progression. Anaemia is prevalent in patients with TB, particularly in sub-Saharan Africa, and associated with increased mortality. Anaemia in TB may be due to inflammation, dietary iron deficiency, or both, and distinguishing among these aetiologies is difficult. Iron supplementation is commonly used to treat anaemia in TB patients, but may be unnecessary if inflammation is the cause. Body iron sequestered by TB inflammation can be mobilized during treatment and used to correct the anaemia. Moreover, supplemental iron may be retained within macrophages, potentially increasing susceptibility to TB and leading to a poorer clinical outcome. Thus, better understanding of iron metabolism during TB and the aetiology of TB-related anaemia would clarify the potential role of iron in pathogenesis and optimal management of the disease. The investigators hypothesize that: a) TB will increase circulating hepcidin and thereby impair dietary iron absorption and systemic utilization of iron, resulting in iron sequestration and anaemia; b) TB treatment and resolution of inflammation over 6 months will decrease circulating hepcidin, correcting these impairments and improving iron status and hemoglobin; c) the majority of iron utilized to replenish hemoglobin during recovery from TB will come from mobilization of sequestered iron stores rather than from iron absorption. Objectives: Use iron stable isotopes to characterize iron balance over six months of TB treatment, and specifically to: a) quantify oral and intravenous iron incorporation (oral absorption and systemic iron utilization) at three time points during TB treatment (acute disease, after the intensive treatment phase and at completion of the continuation treatment phase); and b) determine the effect of treatment on iron mobilization from stores to replenish hemoglobin. Methods/Subjects: Using a triple stable-isotope technique, iron absorption from labelled test meals (57Fe) and systemic iron utilization after labelled intravenous doses (54Fe, 58Fe) will be determined in 18 Tanzanian subjects with newly diagnosed pulmonary TB. The subjects will be studied at three time points (i) the day after TB diagnosis while infected, (ii) after 8 weeks of intensive phase treatment, and (iii) after another 16 weeks of continuation phase treatment. Iron status, hemoglobin, hepcidin and inflammation indexes will be measured at each time point. Isotope enrichment during the two treatment phases will be measured to estimate the relative rates of iron absorption and mobilization from stores during the intensive and continuation phases to determine the relative contributions of iron absorption and iron mobilization from stores during TB treatment and recovery. Outcome: These studies will provide important new insights into the aetiology of anaemia and iron metabolism in TB patients. The results will provide essential data for evidence-based recommendations on the timing, administration route and efficacy of iron therapy in patients with TB, making possible, a safer and more effective treatment of anaemia in TB while decreasing morbidity and mortality from the disease.
Tuberculosis burden in Vietnam increasing with contribution from low detection rates and increased drug resistance. There is a need to identify MDR-TB (MultiDrug Resistant Tuberculosis) among both notified TB cases and their contacts in the community. Traditional contact tracing often focuses on household contacts while strains of TB circulate in homes, schools, workplaces, and beyond. Social network Analysis (SNA) is a comprehensive approach which includes a set of persons and the connections among them used for analysis of structure of disease transmission. In this study, SNA will be used to collect network data from 60 newly detected Rifampicin resistant TB patients including an expected 50 MDR-TB patients living in Hanoi, and to identify and test potential MDR-TB cases.
The diagnosis of tuberculous peritonitis (TBP) is still challenging, and largely dependent on invasive procedures such as laparoscopy. A recently developed RD-1 gene-based assay for diagnosing TBP shows has given promising results. The investigators thus created a 2-step algorithm using the Blood/Ascites ELISPOT assays and adenosine deaminase (ADA) in ascites for differentiation of TBP from other diagnoses (Blood ELISPOT ≥6 spots or ADA ≥ 21 U/L' as a rule-out test and 'Ascites/Blood ratio ≥3' as a rule-in test). This study is the randomized controlled trial on whether this 2-step algorithm-based approach can reduce the laparoscopic biopsy for the diagnosis of TBP in patients with suspected TBP.
The purpose of this study is to determine the effectiveness and cost-effectiveness of a new population-based active case-finding program among adult household contacts of new infectious TB cases to detect active TB cases in the largest district, Lima, Peru.
The goal of this study is to evaluate time to diagnosis for three assays (line probe, pyrosequencing, and Microscopic Observation Drug Susceptibility Assay [MODS]) to detect resistance to first and second-line anti-tuberculosis (TB) drugs in Mycobacterium tuberculosis (Mtb) strains in 7 days or less, allowing for rapid diagnosis of extensively drug-resistant TB (XDR-TB).
Tuberculous meningitis (TBM) is the most severe form of tuberculosis infection with high mortality. Current treatment regimens are not based on clinical trials. Rifampicin is a key drug for TBM, but its penetration into the brain is limited, suggesting that a higher dose may be more effective. There are several highly relevant, outstanding questions related to the appropriate dose of rifampicin for TBM, before a multicenter phase 3 trial can be performed. These are: 1. Previous phase 2a randomized clinical trial (done in the same setting as this proposed study) suggests that high doses of intravenous rifampicin (600mg, circa 13 mg/mg) for TBM is safe and associated with a survival benefit in adults. Given that i.v. rifampicin is not readily available, this needs to be confirmed using an equivalent higher oral dose of rifampicin. 2. Recent pharmacokinetic analysis of a continuation trial comparing 600 mg i.v. rifampicin with 750 mg and 900 mg oral rifampicin suggests that an even higher dose may be needed; but this has not been examined 3. Based on those previous data, there is a need to explore a longer duration of high-dose rifampicin for a subsequent phase 3 randomized clinical trial; treatment response in the investigators previous trial suggest that the optimal duration may be > 14 days. 4. There is a need to explore relevant treatment endpoints besides mortality including neurological, neuroradiological and inflammatory response.
Pakistan ranks fifth amongst high tuberculosis-(TB) burden countries, where TB persists as a major cause of misery and death. The Diabetes Mellitus-(DM) is also on rise in Pakistan and people suffering from DM are more prone to catch TB as compared to healthy individuals. This concurrence of two outbreaks may further increase the frequency of TB in Pakistan. The TB DM co-occurrence results in various clinical issues as TB in DM patient increases blood glucose, making DM more difficult to treat, while DM raises the risk of treatment failure, relapse and death among TB patients. In addition, both DM and TB usually coexist with micronutrients deficiencies like vitamin D, which has a vital role in immunity, insulin functioning and respiratory health. It has been suggested that the combined supplementation with vitamin D and calcium might be beneficial in improving the glucose metabolism but the current knowledge is very limited. In a resource restrained country with double burden of infectious and non-infectious diseases, an integrated approach with modification of treatment options may benefit in management of these outbreaks. Therefore, this study aims whether vitamin D and calcium supplementation could influence the recovery in patients with TB of lung and DM.
This is an open label observational pharmacokinetic drug study to evaluate Levofloxacine and Capreomycin in patients with Multidrug-Resistant Tuberculosis (MDR-TB).
In this longitudinal study with a follow up time of at least 6 months, up to 300 tuberculosis (TB) patients or TB suspects will be screened for TB using the Xpert MTB/RIF assay along with standard smear microscopy after Ziehl-Neelsen staining at the TB health clinic located at Mavalane health center. Confirmed TB cases will be followed up during TB therapy until month six after treatment initiation in order to obtain clinical and microbiological data on treatment including treatment response. Apart from relevant research questions in the field of TB diagnostics and treatment, the main objective of this study will be the development of a clinical TB research site, including capacity development in clinical and laboratory based TB research methods, in Mavalane, Maputo.