View clinical trials related to Tuberculosis.
Filter by:This study is a randomized control trial assessing the impact of a simple evidence-based protocol for the treatment severe sepsis with hypotension in Zambia. This is a follow-up study to the Simplified Severe Sepsis Protocol (SSSP) study. The intervention protocol consists of a scheduled fluid regimen, early blood culture and antibiotics, and dopamine and blood transfusion when necessary. It is hypothesized that the protocol will significantly decrease in-hospital mortality in patients with severe sepsis and hypotension.
- Background and study aims? Some of the drugs used to treat HIV (anti-retrovirals, or ARVs) can affect the blood levels of other drugs used to treat TB - called a "drug-drug interaction". The main drug used in second-line therapy, Aluvia (lopinavir/ritonavir), is one of the drugs that has this effect. This is why people on second-line ARVs usually cannot use one of the main TB drugs, "rifampicin", and instead will be prescribed a slightly different drug called "rifabutin", which is less affected by these drug-drug interactions. Although blood levels of rifabutin are not as badly affected by Aluvia as blood levels of rifampicin, rifabutin levels in the blood are still increased a lot by taking Aluvia at the same time. This could lead to higher levels of side-effects because there is more drug in the body. So in the past doctors have suggested that instead of taking rifabutin every day with Aluvia, it should only be taken three times a week, on Mondays, Wednesdays and Fridays. However, in the last 2 years, new studies have suggested that this three times a week regimen might not be enough and that it may not completely cure TB. So the purpose of this study is to find out whether taking rifabutin every day with Aluvia really does lead to more side-effects, and whether taking rifabutin three times a week with Aluvia really does lead to much lower levels of rifabutin in the blood. - Who can participate? This substudy is specifically for people who are already taking anti-TB drugs in EARNEST, or who need to start anti-TB drugs whilst they are in the EARNEST trial. - What does the study involve? Participants will be selected (by chance, chosen by a computer) to one of the following two rifabutin groups: Group 1: Rifabutin (150 mg) taken three times a week on Monday/Wednesday/Friday Group 2: Rifabutin (150 mg) taken every day On these days, one capsule of rifabutin (150 mg) should be taken in the morning by mouth. Participants will be asked to attend clinic 2 and 12 weeks after entering the sub-study then every 6 weeks until the end of their TB treatment, and then return to their usual EARNEST follow-up schedule. This is roughly the same visit schedule for people with TB who are usually seen more frequently than those without TB, whether or not the patients join this sub-study. The 2 week visit is specifically so the investigators can make sure participants are doing OK on rifabutin and to check carefully that they don't have any side-effects. At all these visits (including the day when participants enroll into the substudy) the investigators will take an extra 10 ml (two teaspoons) of blood to do laboratory tests for side-effects of rifabutin, and to measure the levels of rifabutin and other ARVs in the blood - these are called "pharmacokinetic" or "PK" studies. On the day of these visits, participants should not take their dose of rifabutin until after this blood draw, so the investigators can measure the lowest amount of drug likely in their blood. Instead, participants should bring the rifabutin dose to clinic, so that they can take it straight after the blood draw. At the visit 12 weeks after starting rifabutin, participants will need to stay in clinic for a second blood draw of ~3 ml (half a teaspoon) around 4 hours after they take the rifabutin dose immediately after the first blood draw. We use this second sample to see how quickly rifabutin enters the blood. At this special visit the investigators will make sure participants are first seen as early as possible, so they don't have to stay any longer than necessary for the second blood draw to be taken 4 hours later. After participants have completed their TB treatment they will stay in EARNEST until the end of the trial (144 weeks on second-line therapy). - What are the possible benefits and risks of participating? If participants are allocated to Group 1 (150 mg rifabutin three times a week), there is a risk that they may have lower levels of rifabutin in your blood and this may be less effective at treating the TB. However, participants should have fewer side-effects. In contrast, if participants are allocated to Group 2 (150 mg rifabutin daily), here is a risk that they may get more side-effects, but the levels of rifabutin in the blood should be more than high enough to have a good chance of curing the TB. Having blood taken may cause some discomfort and/or bruising in some people. It is currently impossible to know which rifabutin regimen would be best and participants may find in years to come that they may or may not have received the best treatment. - Where is the study run from? 9 EARNEST sites in Uganda as follows: JCRC Kampala, IDI, San Raphael of St Francis Hospital (Nsambya), JCRC Mbarara, JCRC Mbale, JCRC Kabale, JCRC Kakira, JCRC Gulu - When is study starting and how long is it expected to run? Start 05/03/2012 finish on 31/01/2014 - Who is funding the study? Abbott
This is a cluster Tuberculosis (TB) randomized trial in which enhanced case finding (ECF) strategy will be compared to passive TB case reporting in The Gambia. And that the impact of ECF on community and household transmission of TB will also be assessed. The hypothesis is a cluster randomized trial of an enhanced case finding (ECF) strategy will increase TB case notifications in The Gambia and reduce TB burden in the study area in a cost effective manner. The impact of ECF on community and household transmission of TB will also be assessed. The investigators hope this trial will contribute to this evidence base. The timing alongside a nationwide TB prevalence survey is particularly of benefit as that would provide a baseline for disease burden against which the investigators may be able to compare case notification or case detection in selected clusters
Hypothesis That improving vitamin D status among TB patients will speed the pace of bacteriological cure, and will enhance immune responses to TB infection
Rationale: The Bacille Calmette-Guérin (BCG) vaccine protects children against disseminated tuberculosis (TB) including TB meningitis and miliary TB, but efficacy against pulmonary TB is inconsistent among children and adults. Administration of live attenuated BCG to infants known to be HIV infected is contraindicated by the World Health Organization (WHO), due to the risk of serious vaccine adverse events (BCG disease. Developing countries, which lack capacity for integration of early infant HIV testing with infant vaccination schedules, have not fully implemented the WHO guidelines on BCG vaccination of HIV exposed infants. Newborn infants of HIV infected mothers continue to receive routine BCG before HIV infection has been excluded. Clinical trials of new viral-vectored TB vaccines, including MVA85A, a modified vaccinia virus Ankara (MVA) vaccine expressing the Mycobacterium tuberculosis antigen 85A, have to date enrolled infants who were already vaccinated with routine BCG at birth. However, TB vaccination regimens that depend on newborn BCG will remain unsafe for HIV infected infants. Infants of HIV infected mothers, who constituted 29% of babies born in South Africa in 2009, would benefit from a new TB vaccination strategy, in which BCG is delayed until after HIV infection has been excluded. These HIV exposed infants also have greater increased risk of TB disease. Testing the safety and immunogenicity of MVA85A vaccine prime, followed by selective delayed BCG boost, in HIV exposed newborns, is a critical step towards delivery of a new TB vaccine regimen that is safe and effective for all infants, regardless of HIV exposure. Study Design: Double blinded, randomised, controlled trial. HIV exposed infants will be randomised 1:1 to receive single dose, intradermal MVA85A vaccine or Candin® control at birth. The first 60 infants enrolled in the trial will form a pilot safety cohort for formal Data Monitoring & Ethics Committee (DMEC) safety review. Thereafter, safety and immunogenicity outcomes will be measured in all infants. Study Population: Infants (n=340) born to HIV infected mothers receiving antiretroviral therapy (ART) or Prevention of Mother to Child Transmission (PMTCT) prophylaxis. Sites: Worcester (University of Cape Town) and Khayelitsha (Stellenbosch University), South Africa Study Intervention: Newborn infants will receive 1 x 108 pfu MVA85A vaccine or Candin® control by intradermal injection. Infants confirmed HIV uninfected by HIV PCR will receive BCG Vaccine SSI at 8 weeks of age. Infants confirmed HIV infected by HIV PCR will not receive BCG. Primary specific aims: To evaluate the safety of MVA85A given at birth to HIV exposed uninfected infants. To evaluate the safety of BCG given at 8 weeks of age to HIV exposed uninfected infants, using an MVA85A prime and BCG boost strategy. Secondary specific aims: To evaluate the immunogenicity of MVA85A given at birth to HIV exposed uninfected infants. To evaluate the immunogenicity of BCG given at 8 weeks of age to HIV exposed uninfected infants, using an MVA85A prime and BCG boost strategy. Safety endpoints: Local, regional, and systemic adverse events (AEs) and serious adverse events (SAEs). Immunology endpoints: Frequencies of CD4 and CD8 T cells producing any of 4 cytokines (IL-17, IFN-γ, TNF-α, or IL-2), or polyfunctional combinations of these cytokines simultaneously, following stimulation with antigen Ag85A or BCG, measured by whole blood intracellular cytokine assay (WB-ICS). Specific proliferative capacity of CD8 and CD4 T cells that produce any of the three cytokines (IFN-γ, TNF-α, and/or IL-2) or combinations of these cytokines simultaneously, measured by a novel whole blood 6-day lymphoproliferative flow cytometric assay (WB-prolif). Relative proportions and absolute numbers of peripheral blood myeloid and lymphoid cell subsets, measured directly ex vivo by flow cytometry. Study groups: The first 60 infants enrolled in Study Group 1 will undergo intensive safety evaluation, followed by DMEC review of Day-28 safety data. The DMEC will make a formal recommendation on continuation of enrollment and/or changes to the protocol, based on this safety review. Study Groups 2-5 will be evaluated for clinical safety and immunology outcomes. Statistical Analysis: Cumulative 12-month incidence of local, regional, and systemic AEs, by category, will be compared for HIV exposed uninfected subjects receiving MVA85A vaccine or Candin® control at birth. The sample size has 90% probability of detecting an SAE with a true occurrence rate of 1.5% in infants receiving MVA85A vaccine and 80% power to detect a 15% difference in the rate of non-serious AEs (20% compared to 35%) between the two study arms (p<0.05). Multivariate models will be built to explore longitudinal immunological data and identify independent associations with MVA85A vaccination and covariates of interest.
Tuberculosis (TB) continues to be one of the most serious bacterial infections worldwide and therefore new improved diagnostic tests are needed to help doctors in diagnosing TB. The new skin test is named C-Tb. Like the current tuberculin skin test, PPD, the C-Tb test is injected just under the skin and will, when positive, show redness and/or swelling at the injection site while a negative test will leave no reactions. The investigators hope that this new C-Tb skin test will be more precise (specific) than the PPD test, as the PPD test e.g. may show a reaction if the person tested is BCG vaccinated. The aim of this trial is to test the C-Tb skin test in volunteers suspected of having TB disease. With focus on age, HIV status and CD4 count the following analyses are done (in an overall perspective): - To compare the C-Tb test to a blood test, the QuantiFERON test. - To compare the C-Tb test to the PPD test that is currently being used. - To assess the safety of the C-Tb test.
New approaches are needed to achieve more rapid elimination of dormant mycobacteria and thereby shorten treatment for drug-sensitive and drug-resistant tuberculosis (TB). Dormant mycobacteria are relatively resistant to antibacterial drugs and approaches that enhance immune clearance have the potential to be more effective. Interleukin-4 (IL-4) is a key cytokine in the immune response to TB that may impair the clearance of mycobacteria. We hypothesize that pascolizumab, an anti-IL-4 monoclonal antibody, might be of value as an adjunct to standard treatment. The aims of this trial are to determine whether administration of pascolizumab as an adjunct to standard combination treatment for drug-sensitive TB produces changes in one or more parameters of bacterial or host response (including bacterial clearance, host clinical status, immune response, bacterial and host transcriptomics, lung imaging) that may indicate potential for enhanced sterilization and to confirm the safety of blocking IL-4 (previously demonstrated in healthy volunteers and patients with asthma) in patients with TB.
The aims of this project are to: 1. To evaluate the pharmacokinetics of first line antituberculosis drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) when applying the 2010 WHO/IUATLD dosing guidelines across pediatric populations (0-12 years of age, HIV infected and uninfected, and with varied nutritional status) in Cape Town, South Africa and Blantyre, Malawi. 2. To evaluate an 8-hourly weight band-based dosing strategy for lopinavir/ritonavir using the commercially available lopinavir/ritonavir (4:1 ratio) in children in South Africa receiving rifampicin-based antituberculosis treatment. 3. To evaluate the pharmacokinetics of nevirapine in children in Malawi receiving rifampicin-based antituberculosis treatment.
The objective of this randomized, controlled trial is to determine if adding a protein-calorie supplement (PCS) to the standard treatments for tuberculosis (TB) and HIV will improve health outcomes. The investigators will enroll 180 HIV-positive women with newly diagnosed active TB and without prior anti-retroviral therapy (ART). At baseline, the investigators will conduct dietary interviews, measure body composition, randomize subjects to receive a PCS (plus micronutritional supplements [MNS]) or control (MNS only) for the 6-month duration of anti-TB therapy (ATT) plus an additional 2 mos (8 mos total). Subjects will be followed monthly and have CD4 counts at baseline, 2, 8 and 12 months. At 2 months (i.e., at the end of the 4 drug intensive phase of TB treatment and start of the 2 drug continuation phase), all subjects will be started on anti-retroviral therapy (ART) based on Tanzanian Ministry of Health guidelines (currently: AZT/3TC/efavirenz). The primary endpoint will be change in CD4 count after 8 months (i.e., at end of PCS/MNS intervention and 2 months after completion of ATT).
Tuberculosis (TB) continues to be the most important bacterial infection worldwide and therefore new improved diagnostic tests are needed to help doctors in diagnosing TB. We are investigating a new skin test named C-Tb. Like the current tuberculin skin test (PPD), the C-Tb test is injected just under the skin and will, when positive, show redness and/or swelling at the injection site while a negative test will leave no reactions. The aim of this trial is to test the C-Tb skin test in volunteers. The volunteers are divided into four groups: - Negative control group: Must have no history of exposure to a person with tuberculosis disease. - Occasional contact: Must be in contact with a person with tuberculosis disease between 6 hours/week and 6 hours/day - Close contact: Must be in close contact with a person with tuberculosis disease for more than 6 hours/day for at least five days - Positive control group: Must have a confirmed tuberculosis disease within the last 3 years. The goals of this clinical trial are: - To compare the C-Tb test to a blood test, the QuantiFERON test. - To compare the C-Tb test to the PPD test that is currently being used. - To assess the safety of the C-Tb test.