Lindi Street

Researchers are evaluating the safety and effectiveness of bedaquiline compared to standard treatments in preventing tuberculosis disease among people living with HIV and high-risk close contacts of individuals with drug-sensitive or rifampin-resistant tuberculosis. This study is a seamless Phase II/III, open-label, multicenter trial conducted in regions with a high burden of tuberculosis. The study aims to show that bedaquiline is not less effective than the World Health Organization's recommended regimens in reducing the risk of developing tuberculosis over 72 weeks of follow-up. Participants include adults, adolescents, children, and pregnant close contacts of tuberculosis patients and people living with HIV. Those in the bedaquiline group receive daily doses based on weight and age for four weeks. The comparison groups receive either a three-month weekly regimen of isoniazid and rifapentine or a six-month daily levofloxacin regimen, depending on their exposure to drug-sensitive or rifampin-resistant tuberculosis. The study includes different treatment durations and regimens tailored to specific participant groups and their risks. During the study, participants undergo various assessments including chest X-rays, laboratory tests, and pregnancy tests where applicable to ensure safety. Researchers monitor treatment completion rates and the occurrence of any adverse drug reactions that lead to stopping treatment. The main outcomes measured are safety events by 18 or 36 weeks depending on the group, treatment completion within the set timeframe, and the number of participants who develop tuberculosis up to 72 weeks after starting treatment.

Researchers are evaluating the B-COMPASS, a disease-agnostic computational model designed to predict patient adherence to treatment and identify their support needs across various health conditions. The study aims to validate the B-COMPASS's accuracy, validity, reliability, and effectiveness in improving treatment adherence and healthcare cost-effectiveness. This model is being tested in real-life settings, involving patients with cardiovascular, endocrine, immunology, neurology, oncology, and rare diseases recruited from multiple European countries. Participants will either receive standard care or enhanced engagement through the B-COMPASS intervention. In the intervention group, healthcare providers receive educational materials tailored to each patient's B-COMPASS profile, which guides personalized patient support. Engagement with patients occurs either in person or by phone, depending on each patient's schedule. The study includes iterative refinements of the model based on validation results from six therapeutic areas. During the study, participants will undergo two main data collection points ranging from 2 weeks to 6 months apart to assess the B-COMPASS's predictive accuracy and stability over time. Researchers will evaluate outcomes such as the model's adherence prediction accuracy, validity of patient groupings, identification of support needs, and reliability. The study also measures patient and healthcare provider perceptions of the model and its impact on healthcare utilization costs, aiming to improve patient experience and adherence through tailored support.

This research aims to evaluate the use of nanopore sequencing for breast cancer diagnosis in Tanzania. The study focuses on patients with suspected breast cancer, testing whether nanopore sequencing is not worse than the current standard methods. The goal is to achieve faster and more cost-effective diagnosis, which could improve treatment decisions and outcomes in settings with limited resources. Excess fresh tissue samples from patients will be tested using nanopore sequencing alongside the usual standard of care, which includes histopathology and biomarker analysis for estrogen receptor, progesterone receptor, and HER2 status. The study will also use low-pass whole genome sequencing and DNA methylation to classify breast cancer subtypes. Results from nanopore sequencing could be available within hours at the point of care, but treatment decisions will not be changed based on these results. Participants will have their tissue samples collected during biopsy or surgery after specialist consultation. Researchers will continuously assess the agreement between nanopore sequencing and standard diagnosis, feasibility of the process, and average turnaround time over about a year. The study will measure the accuracy, speed, and practicality of nanopore sequencing as a diagnostic tool for breast cancer in this setting.

Researchers are evaluating the safety and effectiveness of new treatment combinations compared to the standard regimen for adults newly diagnosed with drug-sensitive pulmonary tuberculosis. This phase 2B/C open-label trial involves multiple stages and experimental treatment arms, including drugs like rifampicin, pyrazinamide, moxifloxacin, BTZ-043, alpibectir, ganfeborole, delpazolid, and others. The study aims to find optimized doses and new drug combinations that could improve treatment outcomes in this population. Participants will be randomly assigned to different treatment groups across three stages. Stage 1 compares the control regimen with two experimental rifampicin-containing regimens. Stage 2 adds a new experimental arm with BTZ-043, adjusting participant allocation ratios accordingly. Stage 3 begins after stages 1 and 2 complete recruitment and compares the control arm with two more experimental arms, including one containing alpibectir and ethionamide. Dosages and drug combinations vary by arm, with regimens administered mostly once daily by mouth. During the study, participants will be monitored up to 26 weeks to assess how quickly their tuberculosis cultures convert to negative and to measure changes in the amount of tuberculosis bacteria. Evaluations include clinical exams, chest X-rays, sputum tests, and safety monitoring. The total number of participants planned is up to 390 adults aged 18 to 65. The study includes thorough follow-up to understand treatment effects and safety in this group.

Researchers are evaluating new treatment regimens for pulmonary tuberculosis (TB) to find faster, safe, and effective options compared to the standard 24-week treatment. This trial is conducted by the UNITE4TB consortium, involving universities and pharmaceutical companies across multiple continents. The study includes adults with newly diagnosed rifampicin-susceptible pulmonary TB and aims to identify novel drug combinations and optimal treatment durations that could also work for drug-resistant TB. The trial has two parts: Phase 2B and Phase 2C. In Phase 2B, up to 700 participants will be randomly assigned to one of twelve treatment arms, including the standard 24-week regimen or various 16-week combinations of drugs such as bedaquiline, delamanid, moxifloxacin, BTZ-043, and GSK3036656. Phase 2C will evaluate the best regimens from Phase 2B by testing different treatment lengths of 8 to 16 weeks in up to 1800 participants. Treatments are given orally daily, and some drugs have specific dosing schedules. Participants will be involved for a total of 72 weeks and will undergo regular assessments including sputum tests to measure bacterial levels, imaging, laboratory tests, and safety monitoring. The study will measure the rate of bacterial clearance and favorable clinical outcomes at 48 weeks. Safety will be monitored closely through adverse event reporting and interim analyses to guide decision-making. The trial aims to improve TB treatment by identifying shorter and effective regimens with acceptable safety profiles.

Researchers are studying how individual and societal factors affect health outcomes such as death and the development of chronic diseases across different socioeconomic and healthcare settings. This research also explores genetic influences on non-communicable diseases through both a cross-sectional and a long-term follow-up approach. The study focuses on understanding the impact of the built environment, food and nutrition policies, psychosocial and socioeconomic factors, tobacco use, and the quality of health systems. The study does not involve specific interventions but observes health-related behaviors including diet, physical activity, smoking, and alcohol use. It monitors how societal influences relate to risk factors and the occurrence of chronic diseases like cardiovascular disease and cancer. Genetic factors for non-communicable diseases are also investigated as part of this comprehensive analysis. Participants aged 35 to 70 are followed over an average of 10 years to assess the development of cardiovascular disease and other health outcomes. Researchers collect data on societal determinants, risk factors, and health behaviors, as well as genetic information. The study aims to understand how these elements relate to disease incidence and mortality, considering different health resource settings worldwide.

Researchers are developing and testing a locally tailored intervention called P-KIDs CARE to improve the triage process for children with injuries in Tanzania. This intervention aims to streamline patient assessment, stabilization, and referral at initial medical contact points like health centers and district hospitals. The study focuses on identifying barriers to timely pediatric injury care and improving the system to reduce delays in getting definitive treatment. The P-KIDs CARE intervention includes two main parts: training healthcare providers using the World Health Organization Basic Emergency Care Course, and an online decision support tool adapted for Northern Tanzania to assist with mortality risk assessment and referral decisions. The study involves three phases: gathering data and insights through interviews and focus groups, developing and refining the intervention with community and provider input, and then piloting the intervention at two health facilities. Participants include pediatric injury patients under 18, their families, and healthcare providers. Researchers will collect data on patient outcomes such as mortality, time to definitive care, and morbidity before and after the intervention. They will also assess the feasibility, acceptability, and fidelity of the intervention through surveys and interviews with providers and families. Overall participation involves registry enrollment, interviews, focus groups, surveys, and outcome tracking over several years.

Researchers are evaluating treatment outcomes for esophageal cancer at multiple sites within the African Esophageal Cancer Consortium (AfrECC). This prospective observational cohort study aims to describe the treatments patients receive, including chemotherapy, radiation, chemo-radiotherapy, esophageal stenting, surgery, and supportive care. It also seeks to assess patient-reported outcomes and overall survival related to these treatment approaches. Participants will receive standard treatments based on clinical decisions at participating AfrECC centers. Researchers will collect data on the types of treatments given and monitor the effects of these treatments on patients over time. Patient-reported outcomes will be gathered using questionnaires to evaluate quality of life and other relevant measures during and after treatment. Throughout the study, participants will complete questionnaires to report their outcomes, and researchers will track survival and treatment effectiveness for up to four years. The main outcomes include the proportion of patients receiving various treatments, changes in patient-reported quality of life scores, and median overall survival. This long-term follow-up will help understand the impact of current esophageal cancer treatments in the African setting.

Researchers are investigating a shorter, 6-month treatment regimen using high doses of rifampicin, isoniazid, linezolid, and pyrazinamide compared to the World Health Organization's standard 9-month treatment for tuberculous meningitis (TBM), a serious brain infection with high risk of death and severe neurological problems. This Phase II, randomized, open-label trial aims to evaluate the safety, drug levels, and long-term outcomes of this intensified 6-month therapy versus the standard treatment. Participants include adults and adolescents diagnosed with TBM, with treatment groups balanced by HIV status and disease severity.

Researchers are exploring how very early intensive antiretroviral therapy (ART), with or without a broadly neutralizing antibody (bNAb), may help infants living with HIV achieve HIV remission, defined as having HIV RNA levels below the detection limit of the test. This Phase I/II study focuses on infants born to mothers with presumed or confirmed HIV infection and aims to evaluate the impact of starting treatment within 48 hours of birth. The study includes two groups: infants born to mothers who received little or no antiretrovirals during pregnancy, and infants confirmed HIV positive shortly after birth who started ART quickly. The study tests seven different intensive therapy regimens involving combinations of nucleoside reverse transcriptase inhibitors (NRTIs), nevirapine (NVP), lopinavir/ritonavir (LPV/r), raltegravir (RAL), dolutegravir (DTG), and monoclonal antibodies VRC01 or VRC07-523LS. Treatments are given orally or by subcutaneous injection depending on the drug. The study is conducted in four steps: initial enrollment and evaluation within 48 hours of birth (Step 1), up to 192 weeks of ART treatment with monitoring and possible treatment interruption if virus suppression is achieved (Step 2), close monitoring during treatment interruption for up to five years (Step 3), and re-initiation of ART with ongoing monitoring if the virus returns or other criteria are met (Step 4). Participants will be closely monitored throughout the study with regular HIV testing, physical exams, and assessments of immune health. Safety monitoring will continue for infants who do not have confirmed infection but received initial treatment. Children who maintain viral suppression will undergo analytic treatment interruption and be followed for viral rebound. Outcome measures include the number of participants who reach HIV remission by week 48. The study may last up to five years for some participants, including long-term follow-up through re-treatment and viral monitoring.