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142 active trials for Tuberculosis

ENhance Initiation and Retention in Isoniazid Preventive Therapy (IPT) Care for HIV Study (ENRICH Study)

The purpose of the ENRICH study is to evaluate a combination intervention package (CIP) designed to improve implementation of Isoniazid Preventive Therapy (IPT) among people living with HIV (PLWH) in Ethiopia. The study is a two-arm cluster randomized trial, randomized at the HIV clinic level, which includes 10 HIV clinics in Dire Dawa and Harari, Ethiopia. Clinics are randomized to deliver the combination intervention package (CIP) or standard of care (SOC), with stratification by facility size (<80 or >80 patients enrolled in HIV care per year). The experimental intervention will be delivered to all patients in HIV clinics randomly assigned to CIP who initiated HIV care at the CIP site on or after January 1, 2013 and initiated IPT on or after date of study initiation, July 1, 2013. In HIV clinics assigned to SOC, usual care procedures for provision of IPT will be delivered. Study Aims and Hypotheses Aim 1. Characterize and compare the effectiveness of a combination intervention package with standard of care for IPT provision in Ethiopia. Hypothesis 1.1: IPT initiation for new patients enrolling in HIV care at CIP clinics will be higher than that for newly enrolled patients at SOC clinics. Hypothesis 1.2: Adherence to and completion of IPT for participants initiating IPT at CIP clinics will be higher than that for those initiating IPT at SOC clinics. Aim 1a. Assess acceptability of CIP among participants enrolled in HIV care and healthcare providers at CIP clinics. Acceptability will include: 1) perceived barriers and facilitators of uptake and delivery of the intervention package among healthcare providers, and 2) acceptability and utilization of intervention components as well as the overall intervention package among IPT initiators and non-initiators. Aim 2. Assess the impact of CIP compared with SOC on HIV-related outcomes. Hypothesis 2: HIV-related outcomes for participants receiving IPT at CIP clinics will be superior to outcomes in participants receiving care at SOC clinics. HIV-related outcomes to be assessed include retention in care and, among those participants receiving antiretroviral therapy (ART), adherence to ART and CD4+ count. Aim 3. Assess the safety and tolerability of IPT among HIV-infected individuals under routine program conditions in Ethiopia. Aim 4. Identify patient and program characteristics associated with IPT adherence and completion at SOC sites. Hypothesis 4.1: IPT adherence and completion will be associated with modifiable patient characteristics, including ART status; knowledge and attitudes about IPT; and social support. Hypothesis 4.2: IPT adherence and completion will be associated with modifiable program characteristics, including provider/patient ratio, patient tracking, and patient support groups.

Start: July 2013

Start TB Patients on ART and Retain on Treatment (START Study)

The purpose of the START Study is to identify an effective, cost-effective, acceptable intervention that addresses programmatic, structural and psychosocial barriers to ART initiation and retention during TB treatment, with the ultimate goal of improving health outcomes among HIV-infected TB patients in Lesotho. The study is a two-arm cluster randomized trial, randomized at the TB/HIV clinic level, which includes twelve TB/HIV clinics in Berea district. Clinics are randomized to deliver the combination intervention package (CIP) or standard of care (SOC), with stratification by facility type. The experimental intervention will be delivered to all HIV-infected TB patients in TB/HIV clinics randomly assigned to CIP. In TB/HIV clinics assigned to SOC, usual care procedures for ART initiation and retention will be delivered. Study hypotheses focus on the effectiveness of the CIP on HIV- and TB-related outcomes. Compared to HIV-infected TB patients attending SOC clinics, HIV-infected TB patients at CIP clinics will have superior HIV- and TB-related outcomes, including: Greater ART initiation during TB treatment Shorter time to ART initiation Greater retention in ART care Higher adherence to ART Greater change in CD4+ count Greater TB treatment success (completion and cure) Greater sputum smear conversion Higher adherence to TB treatment Additionally, CIP delivery will have an incremental cost-effectiveness ratio more favorable than alternative resource uses.

Start: April 2013

The Effect of Latent Tuberculosis Infection on the Pregnancy Outcome of IVF-ET

This study evaluate the effect of latent infection of tuberculosis on the pregnancy outcome of IVF-ET in infertile patients with radiographic lesions suggesting old healed tuberculosis

Start: January 2019

Behavior Change and Digital Health Interventions for Improved TB Treatment Outcomes

Each year, 10.4 million patients are diagnosed with and 1.7 million people die from Tuberculosis (TB). Despite the availability of highly effective and accessible medications in the developing world where TB is endemic, the 6-18 month treatment regimen is often thwarted as patients fail to comply due to a lack of knowledge about the disease, desire for privacy, and/or stigma avoidance. Successful TB treatment is critical for reducing transmission, the selection of drug-resistant strains and treatment costs. Mobile health interventions promise to increase treatment success, especially in regions where directly observed treatment (DOT) is impractical. The most promising interventions attempted thus far employ a combination of SMS reminders and medication monitors. However, there is relatively little high-quality evidence on their impact, and what evidence there is shows mixed success. In Kenya, the burden of TB is among the highest in the world with a prevalence rate of 558 cases per 100,000 people. There is a great need for the development of alternative protocols, which reduce the costs of treatment and burden of adherence, and more effectively motivate patients to adhere to the program. A substantial and growing literature in the social sciences demonstrates the potential of behavioral interventions for generating large increases in contributions to public goods. Keheala, a feature-phone and Internet-based digital platform that uses Unstructured Supplementary Service Data (USSD) technology to register a patient's self-verification of medication adherence alongside support and motivation, based on proven techniques from the behavioral sciences, was shown in a 1,200-patient randomized controlled trial (RCT) to reduce the unsuccessful TB treatment outcomes in Kenya by two-thirds compared to the standard of care protocol. This 15,500 patient RCT will compare Keheala's scalability, cost-effectiveness and social impact to alternative interventions across diverse regions of Kenya.

Start: April 2018

Evaluating the Pharmacokinetics, Safety, and Tolerability of Delamanid in Combination With Optimized Multidrug Background Regimen (OBR) for Multidrug-Resistant Tuberculosis (MDR-TB) in HIV-Infected and HIV-Uninfected Children With MDR-TB

This study will evaluate the pharmacokinetics, safety, and tolerability of the anti-tuberculosis (TB) drug delamanid (DLM) in combination with an optimized multidrug background regimen (OBR) for multidrug-resistant tuberculosis (MDR-TB) in HIV-infected and HIV-uninfected children with MDR-TB.

Start: January 2018

Immunological Biomarkers in Tuberculosis Management

Tuberculosis (TB) is the leading cause of death by infectious disease in the world, responsible for 1.6 million deaths in 2017. The treatment of active TB requires at least a 6-month combined antibiotic regimen and can cause heavy side effects. As a consequence, treatment adherence is not optimal, particularly in primary care settings. Rapid and reliable monitoring of anti-TB treatment adherence and efficacy is critical to provide adequate patient care and curb relapse episodes and acquired drug resistance. Investigators propose to evaluate the performance in terms of diagnosis accuracy and outcome prediction of four new biomarkers of active TB: 1) a double IGRA (Interferon Gamma Release Assay) including QuantiFERON-Gold Plus® and HBHA; 2) a whole blood transcriptomic analysis of mRNA (messenger Ribonucleic acid) expression of a panel of 150 genes; 3) a whole blood proteomic analysis; 4) an ex vivo immunophenotyping using flow and mass cytometry to characterize the lymphocyte populations.

Start: September 2019

Lowering InterLeukin-1 Receptor Antagonist Concentrations After TB Treatment Onset

Despite marked improvements in the diagnosis of tuberculosis there are difficulties in diagnosing and monitoring treatment outcome among TB patients. The use of immunological biomarkers alone or in combination with other clinical parameters could predict early the response to TB treatment. The aim of this study is to demonstrate that the IL-1 receptor antagonist (IL-1Ra) concentrations significantly decrease within two weeks following TB treatment initiation in adults with active documented TB.

Start: January 2020

An Evaluation of Traditional Directly Observed Therapy (DOT) and Electronic DOT for TB Treatment

This study is a U.S.-based, 1 site (with 4 clinical settings), randomized controlled trial (with funding from the Centers for Disease Control and Prevention's (CDC) Antibiotic Resistance Solutions Initiative) that will be implemented to evaluate traditional directly observed therapy (DOT) and electronic forms of DOT (eDOT) for tuberculosis (TB) treatment. The trial will assess whether eDOT that employs electronic communication methods, such as video via computer or cellphone, is a non-inferior approach to monitor TB treatment adherence, compared to traditional in-person DOT (ipDOT), in which a trained person is in the physical presence of patients as anti-TB drugs are ingested. ipDOT is the single best intervention proven to be successful when it comes to TB patients' adherence to therapy (which reduces risk of acquired drug resistance). However, ipDOT is resource intensive and many times challenging to facilitate in-person. If eDOT is found to be non-inferior to ipDOT, health departments and other clinicians might be able to provide eDOT to certain populations of TB patients in a more flexible and potentially cost-saving manner.

Start: July 2017

SMS-based Mobile Health Intervention for Nutritional Status and Treatment Outcome Among TB Patients

Ethiopia is one of the high burden Tuberculosis countries and Tuberculosis is still the leading cause of mortality due to communicable diseases in the country. Nutritional status is one of the predictors of TB treatment outcomes. Thus, the current practices need integration of nutritional intervention in the DOT using Mobile health intervention. However, to investigator's knowledge, there is no sufficient evidence on the effect SMS text Messaging Mobile Health intervention on nutritional status and TB treatment outcomes in Ethiopia.

Start: July 2020

Development of a Diagnostic Prediction Score for Tuberculosis in Hospitalized Children With Severe Acute Malnutrition

TB-Speed SAM is a multicentric, prospective diagnostic cohort study conducted in three countries with high and very high TB incidence (Sierra Leone, Uganda, and Zambia). It aims at assessing several diagnostic tests that could result in the development of a score and algorithm for TB treatment decision in hospitalised children with severe acute malnutrition (SAM).

Start: November 2019

Point-of-care Triage Test for Active Tuberculosis

Background: Tuberculosis (TB) is a bacterial lung infection leaving 3.6 million people undiagnosed each year. Thirty percent of infected people do not receive treatment due to failure to receive diagnostic testing or being lost to follow-up between testing and availability of results. Objective: To refine and field-validate a point-of-care (POC) finger stick blood test for use worldwide to triage for active TB. Eligibility: Persons aged 15 - 70 years with symptoms suggestive of TB disease Study design: Participants will be screened with: Medical history Physical exam HIV test, diabetes screening Blood (finger stick and venous), sputum and urine collection Chest X-ray TB positive participants will receive treatment from the National TB Program at Community Health Centres and clinics.

Start: March 2020

TB-Speed - Stool Processing

There is a growing interest for the use of stool samples as an alternative to respiratory samples for the diagnosis of intrathoracic TB in children unable to produce sputum. Unlike respiratory samples, stool samples require processing before molecular testing. Several groups have already evaluated different processing methods. However, it is difficult to know which method has the best accuracy and potential for use at Primary Health Care level, due to the difference in study designs and populations. Therefore, in this study, the investigators propose to evaluate the accuracy of different promising stool processing methods in the same population within the same study with an adapted design. Furthermore, no study has so far evaluated for stool testing the new Xpert MTB/RIF Ultra cartridge that has a lower level of detection than the previous Xpert MTB/RIF cartridge. The investigators propose to evaluate the accuracy of Xpert MTB/RIF Ultra (Ultra) performed on stool samples collected from children with presumptive TB and processed using four different processing methods (Standard sucrose flotation method, optimized sucrose flotation method, SPK, and SOS) against bacteriological results from respiratory specimens and to perform a head-to-head comparison of the diagnostic accuracy and feasibility of these different methods in Uganda and Zambia. The selection of processing methods was based on accuracy results, degree of simplification allowing their introduction at PHC level, and finding from the TB-Speed in-vitro stool processing study. The standard sucrose flotation method is kept to assess if results obtained with the optimised sucrose-flotation method in our in-vitro study can be reproduced in-vivo

Start: January 2020

A Pragmatic Randomised Study to Optimise Screening, Prevention and Care for Tuberculosis in Malawi

A pragmatic open, three-arm individually-randomised controlled trial and economic evaluation will be conducted in one primary health care centre in Blantyre, Malawi, where HIV and TB are major contributors to early mortality. Participants will be adults with symptoms of tuberculosis (cough of any duration) attending the primary clinic with an acute care episode. We will exclude adults who have taken treatment for TB within the previous 6-months, who are taking isoniazid preventive therapy, who are not resident of Blantyre, or who plan to move out of Blantyre in the following 6-months. Participants will be randomly allocated into one of three groups: Group 1: Standard of care: Participants will be seen by facility health workers and receive clinician-directed screening for HIV and TB according to Malawi national guidelines. Group 2: Optimised HIV testing and treatment linkage: Participants will be offered testing for HIV using rapid oral fluid kits by research assistants. Those with confirmed HIV infection will be linked to the HIV care clinic where facility healthworkers will screen for TB using standard sputum-based diagnostics. Group 3: Optimised TB diagnosis, HIV screening and treatment linkage: Participants will receive a high-throughput and high-sensitivity TB screening intervention, in addition to the HIV testing intervention. This will comprise of an initial digital chest x-ray classified by the CAD4TB image-recognition software as either "high probability of TB", or "low probability of TB". Participants whose x-rays are suggestive of TB will receive confirmatory sputum testing with Xpert MTB/Rif Ultra cartridges, whilst participants whose x-rays have a low probability of TB will be referred to facility healthworkers for routine care. All participants will be seen at the health facility at day 56, where they will be tested for HIV (if not on ART) and screened for TB. The Primary Trial Outcome will compare between groups the time to tuberculosis treatment initiation by day 56. The trial is sufficiently powered to permit 3 pairwise comparisons between groups (i.e. Group 1 vs. 2; Group 2 vs. 3; and Group 1 vs. 3). This three-arm pragmatic trial design allows us to efficiently answer two separate, important public health questions: firstly, by comparing Group 2 to Group 1, we should be able to determine whether HIV care should be prioritised for adults with TB symptoms. Additionally, by comparing Group 3 to Group 2, we will provide strong evidence for the effectiveness of an optimised and integrated HIV and TB diagnostic and treatment linkage approach.

Start: November 2018

Evaluation of Centralised TB Assay Solutions

Tuberculosis (TB) remains a life-threatening disease partly due to increasing incidence of multidrug and extensively drug-resistant TB. Diagnostic based on culture and conventional drug susceptibility testing using media take several weeks leading to prolonged periods of ineffective therapy and ongoing transmission. Development of rapid molecular diagnostic tests for the identification of Mycobacterium tuberculosis (MTB) and drug resistance has become a high priority. The Xpert® MTB/RIF Assay does not provide information on INH-resistance and the LPA is only recommended for use in smear-positive samples, complex to perform and requires manual interpretation. Several novel assays have been recently developed/CE-marked offering high sample throughput and higher sensitivity for detection of MTB, RIF- and INH-resistance in centralized laboratories. However, published data on their performance and operational characteristics is extremely limited. This is a prospective, multicentre, diagnostic accuracy trial in which the performance of centralised TB assay solutions will be assessed at the intended setting of use with culture, phenotypic DST and sequencing as reference standard. Potential trial participants will be identified at participating TB clinics or hospitals (enrolment sites). Sputum samples will be collected and transported to the associated TB reference laboratories (testing sites). In order for the results of this trial to be generalizable, adults with symptoms compatible with pulmonary TB undergoing evaluation will be screened for inclusion at geographically diverse participating centres in high burden TB countries. Additionally, to supplement the drug-resistant cases to timely achieve accurate performance estimates, well-characterized frozen sputum samples from the FIND specimen bank will be used.

Start: May 2019

Pharmacokinetics of Atazanavir in Special Populations

The lack of data relating to the DDI between ATV and RIF is a major limitation to the use of ATV in patients who require treatment for TB. The VirTUAL Workpackage 2 will explore the necessary dose escalation required to overcome this interaction in non-pregnant HIV-infected adults who are virologically suppressed on bPI-based ART, and who are administered RIF as a study drug, not as part of a full TB treatment regimen. As the specific objective of WP2 is to define the dose of ATV, participants taking an alternative bPI will be transitioned to ATV for the duration of that study. However, to extrapolate the results of this study to special populations such as pregnant and postpartum women, children and adolescents and those with other 'special' characteristics such as obesity (BMI >30 Kg/m2) or malnutrition (BMI <18.5 Kg/m2) we propose to undertake sparse sampling for pharmacokinetic analysis from individuals who require ATV-based ART for their clinical care. Sparse PK data will be obtained opportunistically from participants in the 'special populations' defined above who are receiving ATV as part of their routine clinical care. Subjects will be identified from clinics including the Joint Clinical Research Center (JCRC) and Infectious Diseases Institute (IDI), Kampala, and from sites including Groote Schuur Hospital and Gugulethu Community Health Centre, Cape Town. The ATV/r data from "special populations" will enable validation and refinement of both the PBPK model (WP1) and the pop-PK models (WP4) of the VirTUAL consortium.

Start: September 2019

Antigen-specific Cytotoxic T Cells in the Treatment of Opportunistic Infections

Epstein Barr Virus (EBV) or Cytomegalovirus (CMV) infection results in significant morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients. HSCT patients often face opportunistic infections due to the immunosuppressive state during transplantation. Antimicrobial drugs are usually used for prophylactic purposes and for treatment after early detectable infections. Unfortunately, some patients develop resistance to such drug treatment. In addition to HSCT patient, immune compromised patient may also be victim to opportunistic infections. Many infections can be effectively managed by functional immune recovery. In this study, the safety and efficacy of microbial-specific cytotoxic T lymphocytes (CTLs) will be investigated.

Start: July 2017

A One-stop Shop for the Same Day Diagnosis and Management of TB and HIV

TB is a major public health problem and the second most common cause of adult death due to infection in many low-income countries. Despite major efforts to de-centralise services, accessibility to diagnosis is still limited, with one third of the 9 million cases occurring each year being missed by national control programmes. New TB diagnostics suitable for use at the point-of-care are emerging. Some of these are intended for screening purposes, as an initial step to identify individuals who may have TB and should undergo further tests for confirmation. These tests may have high sensitivity, but also give false-positive results (low specificity). Other tests aim to be the confirmatory tests for TB (high specificity), but these tests are often more expensive and complex and are only available in hospital laboratories. As these tests have different purposes, it is likely they would work better in combination in a step fashion to optimise their impact and to develop an efficient diagnostic process. Furthermore, as none of the tests is versatile enough to be used in all settings, test combinations will need to consider the health system context in which they would be used. Our aim is to develop and evaluate rapid and accurate diagnostic approaches for TB that facilitate the initiation of appropriate treatment on the same day of the initial consultation in Africa. The objectives are to Evaluate new diagnostics for TB (including among HIV co-infected individuals) that are suitable at the point-of-care; Develop diagnostic algorithms that streamline and accelerate the diagnosis of TB, allowing patients to reach clinical management decisions within a single clinic visit; Determine the impact of using novel point-of-care diagnostic combinations on the proportion of patients correctly initiating TB treatment within 24-48 hours of first attendance; their potential cost effectiveness The investigators conducted studies in 2016-2018 to accomplish the first two objectives and have identified diagnostic tests that are suitable for low and middle income countries. This document therefore refers to objective 3, which aims to Assess the performance of two diagnostic schemes for the diagnosis of TB when compared to culture. Assess the yield of two diagnostic schemes for the diagnosis of TB when compared to Xpert and Assess the cost of the two diagnostic schemes compared to Xpert.

Start: January 2019

Phase 1 Clinical Trial of ID93+GLA-SE Vaccine in BCG-vaccinated Healthy Adolescent

The purpose of this study is to evaluate safety, immunogenicity of ID93+GLA-SE compared to placebo following three intramuscular (IM) injections on Days 0, 28 and 56 in BCG-vaccinated QFT-negative healthy adolescent. The healthy adolescent will all have had the childhood TB vaccine called BCG, and all of them must have a negative result for a blood test for exposure to the bacteria that cause TB (QuantiFERON-TB Gold Plus, or "QFT"). Study participants will be followed for 12 months after the last injection for safety reasons. Blood will be drawn for laboratory tests for safety and immunogenicity tests. The study hypothesis is that the vaccine is safe and immunogenic in this study population.

Start: April 2019

Safety and Efficacy of High Dose Rifampicin in Tuberculosis (TB)-HIV Co-infected Patients on Efavirenz- or Dolutegravir-based Antiretroviral Therapy

Higher doses of rifampicin has been associated with a faster drop in bacterial load over time, and shorter treatment regimens with high dose rifampicin are being proposed. Sub-therapeutic rifampicin concentrations are common in TB patients and have been demonstrated in several studies carried out among patients with tuberculosis receiving the standard dose (10mg/kg) of rifampicin. Insufficient exposure to isoniazid and rifampicin, which are the cornerstones of TB treatment, has been associated with drug resistance, treatment failure and delayed bacterial clearance from sputum. Evidence has indicated that the current dose of rifampicin (10mg/kg) is inadequate for many patients. Several studies have suggested that dose escalation (to 20-35mg/kg) is safe, and that higher doses (35mg/kg) may accelerate clearance of TB bacteria from the sputum of infected individuals and achievement of target concentrations.15,16 However, these studies have almost entirely been conducted among HIV negative TB patients, or TB-HIV co-infected patients without severe immunosuppression who are not yet receiving antiretroviral therapy (ART). TB-HIV co-infected patients on multiple additional drugs, including ART, are at increased risk of drug-drug interactions and drug related toxicities, including hepatotoxicity. Increasing the dose of rifampicin is a promising approach; however, there is paucity of data on the safety of higher doses of rifampicin in HIV infected patients on ART, and almost no information on the enzyme induction effect of high dose rifampicin on Efavirenz (EFV) and Dolutegravir (DTG). In this study, the investigators will not only evaluate for the enzyme induction effect of 35mg/kg of rifampicin on the most widely used first-line antiretrovirals, but will also look at the safety of these combinations in a population in which there is still scarce safety data. The aim of this study is to determine the safety of higher doses of rifampicin and its effect on the pharmacokinetics of efavirenz and dolutegravir in TB-HIV co-infected patients.

Start: April 2019

Real-time Tuberculosis Medication Adherence Intervention in Rural Southwestern Uganda

With an estimated 60,000 people diagnosed with TB (Tuberculosis) annually, Uganda holds the 16th position of the 22 countries with highest cases of TB in the world. The Uganda national target of utilizing the DOTS (Direct Observed Treatment Short Course) to successfully treat 85% of patients diagnosed with TB has not been met. Currently, the country only detects 49.6% TB case detection, of which it successfully treats 73%. The DOTS strategy has suffered many socioeconomic challenges, which have resulted into its abandonment by many of the Ugandan hospitals. Poor TB medication adherence greatly attribute to the many cases of TB in Uganda. Causes of non-adherence to TB medication include lack of patient follow-up, patients' lack of transport to go to the clinics to pick up drugs, patients' forgetfulness. There is evidence that real time adherence monitoring linked with SMS reminders and social support notifications can address barriers to sustained ART (antiretroviral therapy) adherence. Such novel interventions addressing TB medication adherence challenges in low resource settings to date are limited. The prevailing SMS-based studies for TB medication adherence report mixed results, do not strategically link interventions with missed doses, and have largely been implemented in developed countries. To date, little is known about the use of real-time adherence monitoring technologies for TB medication adherence in resource-limited settings. The goal of this research is to investigate the use of real time adherence monitoring technology linked with SMS reminders and notifications for TB medication adherence in rural southwestern Uganda. The investigator will develop and quantitatively test a real-time adherence monitoring intervention with 60 individuals initiating TB treatment, and 40 social supporters. The investigator will randomize participants (1:1:1) to the following arms: 1) Fixed and linked SMS reminders, 2) SMS notifications to social supporters, and 3) no SMS (control). All participants will have adherence monitored in real-time for 6 months.

Start: January 2019