Clinical Research Directory

Isoniazid-Related Hepatotoxicity in Clinical Practice: Incidence and Predictors

The objective of this observational study is to determine how frequently isoniazid (INH) causes liver injury (hepatotoxicity) in adults treated for tuberculosis (TB) or latent tuberculosis infection (LTBI) and to understand which factors increase this risk. The study also aims to describe how hepatotoxicity is managed in real-world clinical practice and whether treatments such as corticosteroids can improve liver function tests. The main questions this study aims to answer are: * How frequently does INH-induced hepatotoxicity occur in adults treated for TB or LTBI? * What demographic, clinical, microbiological, or lifestyle factors increase the risk of developing hepatotoxicity? * How do different management strategies, including treatment modification or the use of corticosteroids, affect liver recovery and completion of TB/LTBI therapy? This study does not involve experimental treatments. Researchers will analyze information already collected during routine clinical care, both retrospectively (from 2020 to 2025) and prospectively (2026-2028). There is no comparison group, but participants may have different clinical profiles or treatments, which will be compared to understand risk factors and outcomes. Participants will: * Receive standard treatment for tuberculosis or LTBI, including isoniazid, as prescribed by their treating physicians. * Undergo routine assessments, such as blood tests, microbiology, imaging, and clinic visits, as part of their regular care. * Their clinical data will be recorded in the study database to analyze liver function trends, treatment changes, and outcomes. The study will contribute to improving understanding of INH-induced hepatotoxicity and supporting safer and more effective treatment strategies for tuberculosis and LTBI.

Pharmacokinetics of Antituberculosis Drugs in Breastfeeding Women

This study is a sub-study of the SSTARLET trial (NCT06498414). The overall aim is to assess the pharmacokinetic profiles after taking a single dose of rifampicin, isoniazid, levofloxacin, rifapentine, and bedaquiline in breastfeeding women and the excretion of these drugs in breast milk, with the hope of including breastfeeding women in future clinical trials of TPT, including expanding the inclusion criteria of the SSTARLET trial. In this study, healthy breastfeeding women who fulfill the eligibility criteria will be enrolled from several primary health care centers in Bandung, which will be referred to the TB Research Clinic of the Universitas Padjadjaran, Bandung, Indonesia. Ten participants will be randomized to each of the following six study arms: * Arm A: Single-dose rifampicin at 10 mg/kg body weight (RIF10). * Arm B: Single-dose rifampicin at 20 mg/kg body weight (RIF20). * Arm C: Single-dose isoniazid at 5 mg/kg body weight (INH5). * Arm D: Single-dose levofloxacin at 10-15 mg/kg body weight (LFX10-15). * Arm E: Single-dose rifapentine at 10 mg/kg body weight (RPT10). * Arm F: Single-dose bedaquiline at 400 mg (BDQ400).

Window Prophylaxis for Pediatric Tuberculosis Prevention Trial

The goal of this cluster-randomized controlled trial is to evaluate the effectiveness of tuberculosis preventive treatment (TPT) administered during the "window period" to prevent new Mycobacterium tuberculosis infections in children and adolescents. The main question it aims to answer is: Can immediate TPT reduce the incidence of IGRA conversions in children and adolescents who are household contacts of a newly diagnosed pulmonary tuberculosis patient? Researchers will compare the incidence of new tuberculosis infections-measured by IGRA conversion at 12 weeks-between participants who receive immediate TPT while still uninfected (baseline IGRA-negative) and those who receive standard care, in which TPT is not offered to IGRA-negative contacts. Participants will be: 1. Tested for M. tuberculosis infection using the Interferon-Gamma Release Assay (IGRA), specifically the QuantiFERON-TB Gold Plus, at enrollment and after 12 weeks of follow-up. 2. Take weekly isoniazid and rifapentine for 12 weeks if: 1. They are assigned to the intervention arm (regardless of baseline IGRA result), or 2. They are in the control arm and test IGRA-positive at baseline. Additionally, participants from the control arm who experience an IGRA conversion at 12 weeks (following the primary outcome assessment) will also receive TPT, as per standard of care.

Safety and Tolerability of 1 Month Daily (1HP) and 3 Months Weekly (3HP) Isoniazid and Rifapentine With Pharmacokinetics of Dolutegravir (DTG) in Pregnant People With HIV

Open-label, two-arm, randomized multicenter study to investigate the safety, tolerability, and pharmacokinetics (PK), and potential interactions between dolutegravir (DTG) and rifapentine (RPT) during pregnancy in people with HIV when RPT is given with isoniazid (INH) daily for 4 weeks (1HP) or weekly for 3 months (3HP) as part of tuberculosis (TB) preventive therapy (TPT). Adults (age ≥18) who are pregnant with a singleton pregnancy (confirmed by ultrasound) at a gestational age of 20-34 weeks and virally suppressed on an existing DTG-based plus two nucleoside reverse transcriptase inhibitors (NRTI) antiretroviral (ART) regimen for at least four weeks may participate.

Dolutegravir Pharmacokinetics Among HIV/TB Coinfected Children Receiving Standard and High-dose Rifampicin

Tuberculosis (TB) is the leading cause of death among children with HIV, yet insufficient data are available on the pharmacokinetics of newer HIV/TB cotreatment strategies in children. Current WHO-recommended rifampicin dosages result in low concentrations in most children, and high-dose rifampicin may improve outcomes and shorten treatment duration. Yet the impact of high-dose rifampicin on dolutegravir exposures has not been examined in children. This study aims to evaluate the safety and pharmacokinetics of dolutegravir twice daily among HIV/TB coinfected children receiving standard-dose and high-dose rifampicin.

Closing -TB GAPs - for People Living With HIV: TB Guidance for Adaptable Patient-Centered Service

Tuberculosis (TB) is the world's leading infectious cause of mortality and responsible for 1/3 of deaths in people living with human immunodeficiency virus (PLHIV). Children and adolescents living with HIV (CALHIV) are disproportionately affected due to inadequate preventive services, large case detection gaps, treatment and adherence challenges, and knowledge gaps. This project will generate evidence to inform interventions targeting several of these weaknesses in the TB/HIV cascade of care. Early detection and treatment of TB improve outcomes in people living with HIV (PLHIV). A key challenge in the detection of HIV-associated TB has been the implementation of screening that identifies the correct population for diagnostic testing. Increasing evidence demonstrates the poor performance of recommended symptom screens and diagnostic approaches. Hence, the investigators aim to define a more accurate TB screening and testing strategy among PLHIV (Objective 1 and Objective 2). TB preventive treatment (TPT) averts HIV-associated TB. Nevertheless, among PLHIV, TPT initiation and completion rates are sub-optimal and effective delivery strategies are not defined. As such, the investigators aim to identify the most effective TPT delivery strategy through shared decision making and by integrating approaches proven to be effective at improving HIV treatment adherence (Objective 3). Although evidence demonstrates that isoniazid preventive therapy (IPT) is cost-effective in young children living in TB/HIV high burden settings, the cost-effectiveness of newer short-course TPT has primarily been studied in the context of a TB low-burden, high-income setting. The investigators aim to generate evidence to fill this knowledge gap and inform policy for PLHIV living in TB/HIV high burden settings (Objective 4). This study is supported by the Centers for Disease Control and Prevention of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award totaling an anticipated $5,000,000 over five years with 100 percent funded by CDC/HHS.

Short-course Regimens for the Treatment of Pulmonary Tuberculosis

The purpose of this study is to determine whether one or two 17-week regimens of tuberculosis treatment bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z)-- (BMZ) plus either Rifabutin (Rb) or Delamanid (D or DLM) are as effective as a standard six-month regimen for treatment of pulmonary tuberculosis (TB). All three regimens are administered daily, seven days each week. The first 17-week regimen is 2 months of bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z), (BMZ) plus rifabutin (Rb) (BMZRB) followed by 2 months of bedaquiline (B or BDQ), moxifloxacin (M) and Rifabutin (Rb) (2 BMZRb/2 BMRb, Arm 1) The Second 17-week regimen is 2 months of bedaquiline (B or BDQ), moxifloxacin (M), pyrazinamide (Z), (BMZ) plus delamanid (D or DLM); (BMZD) followed by 2 months of bedaquiline (B or BDQ), moxifloxacin (M) and delamanid (D or DLM) (2 BMZD/2 BMD, Arm 2) The standard 26-week treatment control regimen which is two months of isoniazid, rifampin, ethambutol, and pyrazinamide (2HRZE) followed by four months of isoniazid and rifampin (4HR); (2HRZE/4HR, Arm 3) Target enrollment is 288 male and female participants (96/arm). participants. Participants will be followed until 78 weeks post-randomization, or until the last enrolled participant completes 52 weeks post-randomization, whichever comes first.

Testing Health Workers At Risk to Advance Our Understanding of TB Infection

It has been estimated that 1.7 billion people have tuberculosis (TB) infection; yet current tests are unable to predict which people are at highest risk of developing TB disease, which can be life-threatening. THWART-TB is a prospective longitudinal cohort study of health workers (HWs) in Cape Town, South Africa, where our preliminary data reveals HWs have a high annual TB infection risk (34%). This cohort, who will undergo frequent serial evaluation (every 3 months) with a combination of novel assays never previously evaluated together, presents a unique opportunity to evaluate immune responses at the time of initial infection and to characterize the dynamic profile of these immune responses over time in a high-risk population. The knowledge generated will improve our understanding of TB infection and help to identify which people exposed to TB may remain at risk, enabling us to better target preventive strategies.

1HP Versus 3HR in the Treatment of Tuberculosis Infection in Vietnam

Introduction: Tuberculosis (TB) infection is a key driver of the TB pandemic, with over 10.6 million people fell ill with TB disease in 2022. About one-quarter of the global population is estimated to be infected with TB bacteria. Around 5-10% of people with TB infection will develop active and contagious TB disease, which could be largely avoided if TB infection is identified and given effective preventative treatment, before progression to active disease. The long treatment of TB infection with regimens lasting from three to nine months is a significant barrier to treatment completion in individuals with a confirmed diagnosis of TB infection. Adapting a shorter regimen than the current regimens could lead to a higher treatment completion rate and increased uptake of preventative therapy for TB, as well as reduced side effects. Methods and analysis: An open-label, randomized clinical trial (1:1) will be performed in two study sites in Ha Noi, Vietnam (Vietnam National Lung Hospital and Ha Noi Lung Hospital). Adult household contacts (n=350) of people with new, bacteriologically-confirmed, pulmonary, drug-susceptible TB who initiate treatment will be invited to participate. Aim: To compare the TB preventive therapy completion rates and adverse event incidence between a new one-month regimen (1HP) versus the current three-month regimen (3HR)\*. \*1HP= one month of daily isoniazid (H/INH) and rifapentine (P/RPT) 3HR= three months of daily isoniazid (H/INH) and rifampicin (R/RIF)

Effects of Tuberculosis Infection on Development and Function of the Placenta

The goal of this observational study is to understand how tuberculosis (TB) infection impacts the function and development of the placenta, and whether TB infection can contribute to pregnancy-related disorders through effects on the placenta. The main questions it aims to answer are: * Does TB infection affect the structure of the placenta? * Does TB infection affect the function of the placenta? Pregnant women attending delivery clinics in Addis Abeba, Ethiopia, will be enrolled and classified for TB infection using a blood-based test. We will compare the following outcomes between women with TB infection and women without TB infection: * Pathological lesions of the placenta * Gene and protein expression patterns linked to pregnancy-related disorders * Infant outcome at birth and at 6 weeks after birth

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.

Analysis of Liver Injury Risk Factors in a Multiethnic Population Treated With Antituberculosis Drugs

Tuberculosis (TB) is the world's second leading cause of death from a single infectious agent after COVID-19. In 2022, TB was estimated to have affected 10.6 million people, of whom 1.3 million died because of it, despite the WHO's implementation of the "End TB" program. Although the gold standard therapy is effective, it may lead to adverse events, among which hepatotoxicity is the most common. Due to its frequency, severity, and potential outcome, anti-TB drug-induced liver injury (DILI) is extremely concerning. Despite decades of use and the large number of patients exposed to anti-TB drugs worldwide, the pathogenesis underlying DILI remains poorly understood. Investigation of drug-related, host genetic, and environmental factors associated with hepatotoxicity susceptibility, as well as studies examining potential mechanisms causing DILI, may help clinicians develop strategies for reducing the incidence of hepatotoxicity. The aim of this study was to determine host- and drug-related risk factors and their association with hepatotoxicity in a multiethnic population in order to enable early identification of individuals with increased susceptibility to anti-TB DILI. An improved understanding of these factors may help to predict and prevent the occurrence of DILI and develop more effective treatments.

Safety and Tolerability of Chlorquine in Addition to Anti-tuberculosis Therapy

In vitro and in vivo data show promising results of adjunctive use of Chloroquine to standard tuberculosis therapy as Chloroquine enhances animicrobial effectiveness against intracellular MTB. To date, no safety data of the concurrent use of both treatments is availble. In a phase I trial, the investigators aim to evaluate safety and tolerability of the concurrent use of Chloroquine and standard anti-TB drug in healthy volunteers.

Multicenter Italian Cohort Study on Tuberculosis in Pediatric Age

According to the WHO report of 2021, approximately 10 million new cases were reported in 2020, of which 1 million occurred in the pediatric population. However, epidemiological data available on tuberculosis (TB) in pediatric age are extremely limited due to diagnostic challenges in this patient category. Furthermore, children are almost never included in national surveillance systems due to the lack of connections between individual pediatricians, pediatric hospitals, and national surveillance programs. It is therefore reasonable to assume that the disease may be significantly underestimated both in Italy and worldwide.

Prevalence of Latent Tuberculosis Infection in Health-care Workers and Students

This study is a cross-sectional study that examines the prevalence of Latent Tuberculosis Infection \[LTBI\], defined as individuals infected with Mycobacterium tuberculosis with no clinical evidence of disease, and the possible risk factors of LTBI in a large cohort of health care workers (HCWs) and students.