Kampala

Researchers are evaluating a family-centred approach to prevent cardiovascular diseases (CVD) among adolescents and their families in Uganda. This study addresses the growing challenge of non-communicable diseases like hypertension, diabetes, and heart disease, which are linked to modifiable behaviors such as diet and physical inactivity. Adolescence is a critical time for adopting healthy habits that can last into adulthood, so the study focuses on this age group to reduce future CVD risk. The research team includes partners from Uganda, Canada, the USA, and the UK, with guidance from Uganda's Ministry of Health. The study compares two groups: one receiving the FaCe-D intervention, which includes home visits with diet, physical activity, and health messaging delivered by Village Health Teams (VHTs), and a control group receiving standard care from VHTs that involves regular health promotion visits but may not engage the whole family. The intervention will be adapted from a previous successful program in Asia and the UK, tailored to Uganda's local context. The study is planned to take place over five years in 32 villages starting in April 2024, with phases for adapting, implementing, and evaluating the intervention. Participants aged 10 to 19 years and their families will be involved for at least 12 months. Researchers will assess changes in cardiovascular health by measuring behaviors, diet, physical activity, and blood pressure. Village Health Teams will support the intervention, and the study will track how well the approach is adopted, its feasibility, and costs. The main outcome is ideal cardiovascular health after one year of follow-up. The study also monitors participants for safety and effectiveness during this time.

Researchers are evaluating new medicines to prevent Human Immunodeficiency Virus Type 1 (HIV-1) infection, focusing on women assigned female at birth who are cisgender. This Phase 3 clinical trial aims to determine whether taking the drug MK-8527 once a month is more effective than the usual daily pre-exposure prophylaxis (PrEP) medication in preventing HIV-1 infection. The study also seeks to understand the safety and tolerability of MK-8527 in this population. Participants will be randomly assigned to receive one of several oral tablets: MK-8527 once monthly, a standard daily PrEP medication called Emtricitabine/tenofovir disoproxil (FTC/TDF), or placebo tablets matched to each drug. This double-blind study compares these groups to assess both the effectiveness and side effects of MK-8527 over time. During the study, participants will be monitored for up to about two years to track new HIV-1 infections, any adverse events they experience, and whether they stop taking the study medication due to side effects. Researchers will regularly evaluate participants' health, safety, and adherence to the treatment plan throughout this period.

Researchers are evaluating how well etavopivat works to reduce the number of vaso-occlusive crises (painful blood vessel blockages) in adolescents and adults living with sickle cell disease. The study also aims to assess if etavopivat can decrease organ damage, improve exercise tolerance, and reduce fatigue. This is a global Phase 3 study involving participants aged 12 years and older with confirmed sickle cell disease. The study is randomized, double-blind, and placebo-controlled to ensure accurate evaluation of the treatment effects. Participants will receive either etavopivat or a matching placebo by mouth. Which treatment they receive is determined randomly. The study will last about two years, during which participants will take the assigned medication and be monitored closely. Etavopivat is an investigational drug currently under evaluation in multiple studies for sickle cell disease. During the study, participants will have regular assessments including documentation of vaso-occlusive crisis events, blood tests, and physical evaluations. Researchers will track the number of crises that require medical attention over a 52-week period, as well as measures of organ health, exercise ability, and fatigue. Safety and overall health will be monitored throughout the study, with the total participation time lasting approximately two years.

Researchers are evaluating the efficacy and safety of inavolisib combined with Phesgo compared to placebo with Phesgo as maintenance therapy in participants who have previously untreated HER2-positive advanced breast cancer with PIK3CA mutations. This Phase III, multicenter, randomized, double-blind, placebo-controlled study focuses on participants with locally advanced or metastatic breast cancer, aiming to understand the treatment impact after initial induction therapy. Participants will receive inavolisib orally once daily on Days 1 to 21 of each 21-day cycle, starting on Day 1 of Cycle 1 during maintenance treatment. Phesgo will be administered subcutaneously every three weeks on Day 1 of each cycle. The study includes an induction therapy phase where taxane-based chemotherapy is given after Phesgo. Optional endocrine therapy such as tamoxifen, aromatase inhibitors, or fulvestrant may be used based on the investigator's choice, with luteinizing hormone-releasing hormone agonists administered according to local guidelines. During the study, participants will be monitored for progression-free survival for up to approximately 40 months. Assessments include evaluation of heart function, organ function, and overall health status. Researchers will track the safety and effectiveness of the treatment combination through regular clinical evaluations and laboratory tests. The total duration includes maintenance treatment cycles and follow-up to measure outcomes and monitor safety.

Researchers are investigating the safety and effectiveness of crizanlizumab compared to a placebo in adolescents and adults aged 12 years and older who have Sickle Cell Disease and experience frequent vaso-occlusive crises (VOCs). This phase III, multicenter, randomized, double-blind study includes patients who have had between 4 and 12 healthcare professional-managed VOCs in the past year. Participants may or may not be taking hydroxyurea or hydroxycarbamide therapy alongside the study treatment. Participants will be randomly assigned in a 2:1 ratio to receive either crizanlizumab at a dose of 5 mg/kg or a placebo, both given as intravenous infusions. The randomization is stratified based on whether they are using hydroxyurea/hydroxycarbamide and by geographic region (South America, North America, and sub-Saharan Africa). Crizanlizumab and placebo are provided in single-use vials for infusion. Treatment will be monitored over a planned period of at least 52 weeks. Throughout the study, participants will be closely monitored for the number of VOCs that require healthcare professional management, including those handled in a healthcare facility or remotely, over one year. Medical history, laboratory tests, and other assessments will be used to document VOCs and evaluate safety. Participants who are on hydroxyurea/hydroxycarbamide or erythropoietin stimulating agents must maintain stable doses during the study. The study aims to assess both the rate of VOCs and the overall safety profile of crizanlizumab in this patient population.

Researchers are evaluating continued access to study drugs for children and adolescents living with HIV-1 who completed participation in previous Gilead clinical studies. This open-label, single-arm Phase 4 study aims to provide these participants with ongoing treatment or switch them to a specific combination drug called bictegravir/emtricitabine/tenofovir (B/F/TAF). The study also monitors the safety of these HIV treatments in this population. Participants receive one of several oral medications including various doses of F/TAF, E/C/F/TAF, Cobicistat, B/F/TAF, or a third antiretroviral agent as determined by their investigator. Dosage forms include fixed-dose combination tablets and tablets for oral suspension, with doses adjusted as needed. Study drugs are provided continuously to eligible participants who completed prior Gilead parent studies. The study focuses on maintaining effective treatment while observing for any adverse effects. During the study, researchers track how many participants receive access to the study drugs over up to 9.5 years. Participants are monitored for side effects and safety through regular assessments. The study collects data on adverse events and laboratory results to evaluate how well the treatments are tolerated. This long-term follow-up helps understand safety in children and adolescents with HIV-1 receiving these therapies.

Researchers are evaluating the ADUNU program, a district-based initiative in Northern Uganda aimed at the secondary prevention of Rheumatic Heart Disease (RHD). This study focuses on assessing the feasibility, sustainability, and public health impact of decentralized RHD preventive services. The program is a non-randomized experiment designed to demonstrate its reach, effectiveness, adoption, implementation, and maintenance using the RE-AIM framework, as well as to estimate its cost-effectiveness and budget impact. The ADUNU program will be implemented by the Ugandan Ministry of Health in partnership with District Health Offices in two districts. It includes community and facility-based echocardiographic screening for RHD among children and young adults and a registry-based system for providing secondary prophylaxis injections of Benzathine penicillin G at local health centers (HCIIIs and HCIVs). The program integrates echocardiography into primary healthcare and maintains patient linkage to care through the registry. Participants will be residents or healthcare providers in the two involved districts. The study involves monitoring program adoption and implementation at organizational, provider, and patient levels with surveys and interviews conducted at baseline, 6 months, 24 months, and 5 years. Researchers will measure retention and adherence to treatment at 12 and 24 months and perform a cost analysis at 3 years. Overall, the study aims to track the program's impact on RHD care delivery over multiple years.

Researchers are evaluating a phone-based tobacco cessation program for people living with HIV (PLWH) in Uganda and Zambia. This study compares the tailored short message service (SMS) intervention to the standard care of brief advice to quit and nicotine replacement therapy using nicotine patches. The trial aims to understand the effectiveness, feasibility, affordability, and applicability of delivering tobacco cessation support through healthcare professionals at HIV treatment centers in two countries with differing tobacco use patterns and healthcare resources. Participants receive either nicotine patches or enrollment in a texting app as part of the cessation interventions, with the study assessing these approaches over time. The program uses a previously tested SMS platform designed to be scalable in low- and middle-income countries. This is the first randomized controlled trial to evaluate this tailored SMS approach among PLWH in these African settings. During the study, researchers monitor participants for prolonged tobacco abstinence over six months following enrollment. The study includes assessments to track tobacco use status and examines the program's impact on quitting success. The findings will provide important information to healthcare providers and policymakers about cost-effective tobacco cessation strategies for PLWH in resource-limited settings.

Researchers are evaluating an enhanced care package for adults with advanced HIV disease (CD4 count below 200 cells/µL) in Uganda. This Phase III, cluster randomized trial aims to compare 24-week survival rates with retention in care between the enhanced package and the standard of care. The study addresses delays in lab-based CD4 testing that can postpone antiretroviral therapy (ART) initiation and screening for opportunistic infections (OIs), which often leads to severe complications and hospitalizations. The intervention group receives point-of-care CD4 testing using the Visitect lateral flow assay along with an enhanced screening and prevention package for opportunistic infections. This includes more sensitive tests such as FujiFilm SILVAMP TB LAM and Cryptococcal Antigen semi-quantitative LFA, plus a shorter, intensive tuberculosis preventive therapy (1 month of isoniazid and rifapentine) and treatment for severe cryptococcal infections if indicated. The control group undergoes standard CD4 testing by flow cytometry and receives the World Health Organization's recommended OI screening and prophylaxis, including urine TB LAM, 6 months of isoniazid, and fluconazole for asymptomatic cryptococcal antigen positivity. Participants will be monitored over 24 weeks for their survival and retention in care. Assessments include CD4 counts, OI screening, and treatment adherence, with the goal to reduce delays in treatment initiation and improve outcomes. The study spans 5 years and randomizes four clinics to either intervention or standard care, with ongoing follow-up to measure the effectiveness and safety of the enhanced package in real-world community settings.

Researchers are evaluating the safety and effectiveness of a new short 6-week daily rifapentine treatment compared to the standard 12-16 week rifamycin-based treatments for latent tuberculosis infection (LTBI). This trial focuses on people at higher risk of developing active tuberculosis and is conducted in various settings with different TB incidence rates. The study aims to test if the shorter treatment is not worse than the longer standard treatments in terms of safety and effectiveness. Participants are randomly assigned to either the experimental group receiving 600 mg of rifapentine daily for 6 weeks or to a control group receiving one of three standard treatments: 12 weeks of once-weekly rifapentine and isoniazid, 12 weeks of daily rifampin and isoniazid, or 16 weeks of daily rifampin. Dosage adjustments are made based on patient weight according to established guidelines. A total of 1,120 participants will be assessed for safety and 3,400 for effectiveness, followed for 24 months after enrollment. During the study, participants will be monitored for treatment discontinuation due to adverse drug reactions and for the development of tuberculosis. Safety and effectiveness will be evaluated by comparing the rates of drug discontinuation and new TB cases between the two groups. Follow-up includes clinical assessments and laboratory tests over a 24-month period to ensure comprehensive monitoring of participant health and treatment outcomes.