Blantyre

Acute hypoxemia, a serious condition with low blood oxygen, often leads to high death rates in resource-limited hospitals. Researchers are evaluating whether high flow oxygen therapy compared to standard flow oxygen improves survival in adult patients with this condition in five hospitals across low and lower-middle income countries. The study also explores challenges and benefits related to using high flow oxygen and compares oxygen usage between the two methods. Participants will be randomly assigned to receive either humidified and heated high flow oxygen through a large nasal cannula targeting oxygen saturation between 90-94%, or standard flow oxygen delivered via nasal cannula, facemask, or non-rebreather mask with the same oxygen saturation target. This comparison aims to determine if one oxygen delivery method leads to better patient outcomes or is more practical to use in these settings. During the study, researchers will monitor patient survival up to 90 days after hospital admission. They will also gather information on oxygen consumption and factors influencing the use of high flow oxygen devices. Patients will be assessed for oxygen levels, treatment adherence, and overall condition throughout their hospital stay to understand the effectiveness and feasibility of both oxygen therapies.

Researchers are evaluating the safety and pharmacokinetics of ambulatory antibiotic treatments for newborns with "all-risk" asymptomatic congenital syphilis. This phase II, randomized, open-label study aims to understand how these treatments behave in the body and their safety profile in this vulnerable population. The study focuses on infants born to mothers with various levels of syphilis risk during pregnancy, including untreated or inadequately treated cases. The study compares three antibiotic treatments: a ten-day course of oral Linezolid at 10 mg/kg twice daily, a ten-day course of oral Amoxicillin at 50 mg/kg twice daily, and a single intramuscular dose of Benzathine Penicillin G at 50,000 IU/kg. Participants receive one of these treatments during the study period. Throughout the study, researchers will monitor the time the antibiotics remain above the minimum inhibitory concentration (MIC) in blood serum and cerebrospinal fluid over 10 days. Safety is assessed by tracking adverse events from enrollment through 24 weeks. Participants will be evaluated through clinical assessments and monitoring to ensure treatment tolerability and to collect relevant pharmacokinetic data.

Researchers are investigating why COVID-19 has caused much lower illness and death rates in sub-Saharan Africa compared to Europe and the Americas. The study focuses on understanding the immune system characteristics of people in Malawi and how factors like malaria, intestinal parasites, and nutritional deficiencies might influence the risk of SARS-CoV-2 infection, disease progression, and vaccine response. The study aims to identify predictors of infection and disease among close contacts of COVID-19 patients, evaluate innate immune responses, and assess the effects of other infections on immune responses to the virus and vaccines. Up to 200 symptomatic COVID-19 patients, about 700 household contacts, and up to 600 vaccine recipients will be enrolled. The study will analyze immune cell responses and antibody levels over time, following infected participants and vaccinees for up to 1.5 years. Participants include those with confirmed SARS-CoV-2 infection and those receiving the AstraZeneca or Johnson & Johnson vaccines. The study will compare immune responses in Malawi with those from Western populations to understand protective factors. Participants will undergo regular visits for up to 15 months to measure antibody levels, immune cell activity, and infection risk. Researchers will collect blood samples and monitor symptoms, immune markers, and vaccine effects. The study will also track how long neutralizing antibodies last and how immune cells respond to infection and vaccination. Safety and adherence to study procedures will be monitored throughout the study period.

Researchers are evaluating the safety of a single intravenous dose of 6-diazo-5-oxo-L-norleucine (DON) in healthy adults, adults with uncomplicated malaria, and children aged 12 months to 14 years with cerebral malaria. This Phase I/IIa study aims to understand the pharmacokinetics of DON in children with cerebral malaria and assess its effects on brain blood flow, brain swelling as seen on MRI, and brain activity patterns on EEG. The study also explores the metabolic mechanisms of DON when given alongside standard malaria treatments. The study includes two parts: an open-label dose escalation in healthy adults and adults with uncomplicated malaria, and a randomized placebo-controlled dose escalation in children with cerebral malaria. Adults will receive one intravenous dose of DON at increasing doses (0.1 to 10 mg/kg) with premedication of ondansetron, while children will receive either DON at 0.1 or 1.0 mg/kg or placebo along with standard anti-malarial therapies including intravenous artesunate and oral lumefantrine-artemether. The pediatric phase will enroll participants over three malaria seasons with up to four cohorts receiving different dose randomizations. Participants will be closely monitored for adverse events within 14 days of DON administration, including local and systemic side effects. Assessments include brain imaging, blood tests, electroencephalograms, and transcranial Doppler ultrasounds to track brain blood flow and volume changes. The study duration is six months for both adults and children, allowing for extended safety evaluations and follow-up monitoring.

Researchers are evaluating the long-term use of a long-acting injectable drug called cabotegravir (CAB LA) for HIV pre-exposure prophylaxis (PrEP) in people at risk of acquiring HIV. This study focuses on participants who have completed or are currently enrolled in previous related studies HPTN 083 and HPTN 084 and their sub-studies. The goal is to monitor new HIV infections, serious adverse events, injection site reactions, and other adverse events that might cause withdrawal over an extended period. Participants will receive CAB LA by gluteal intramuscular injection at a dose of 600 mg every 8 weeks. This treatment continues from the parent studies, and participants will be followed for up to approximately 3 years. The study includes ongoing treatment with CAB LA and regular assessments to evaluate safety and effectiveness as part of this long-term follow-up. During the study, participants will undergo regular HIV testing, safety monitoring, and evaluation of injection site reactions and adverse events. Researchers will track the number of new HIV infections and detailed characteristics of these infections from the start of the study through the follow-up period. This includes monitoring serious and grade 3 or 4 injection site reactions, as well as other adverse events that may lead to withdrawal from the study. Participants will be observed closely to ensure continued safety throughout the study duration.

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 the safety and effectiveness of pramipexole extended release (ER) compared to escitalopram for treating major depressive disorder (MDD) and MDD with mild neurocognitive disorder (MND) in people living with HIV. This phase II, randomized, open-label trial includes an optional sub-study with 36 participants to assess treatment effects on cerebrospinal fluid (CSF) profiles. Participants will be carefully monitored to track treatment response and any side effects. Participants will take either pramipexole ER tablets or escitalopram tablets, both taken orally. The study includes scheduled visits for detailed and brief assessments throughout treatment to check for toxicity, response, and dose adjustments as needed. The sub-study for CSF evaluation is optional and involves a smaller group of participants. During the study, participants will undergo evaluations including the Beck Depression Inventory-II to measure changes in depression symptoms from the start to week 24. Researchers will also monitor for any severe or neuropsychiatric adverse events related to the study drugs throughout the 24 weeks. Participants will be assessed regularly to ensure safety and to observe treatment effects over the study period.

Infections are a leading cause of newborn deaths, with Group B Streptococcus (GBS) being the primary cause of sepsis and bacterial meningitis in infants during their first 90 days of life. Researchers are preparing for late-phase clinical trials of GBS vaccines designed for pregnant women to protect their unborn babies. The PROTECT project supports medical sites in Kenya, Malawi, Mozambique, and Uganda to establish uniform data collection and surveillance systems for GBS and other infections, aiming to improve vaccine trial readiness and vaccine safety monitoring in these regions. The study focuses on three main areas: establishing pregnancy exposure registries using electronic health records to track pregnancy and infant outcomes; developing sentinel site surveillance for laboratory-confirmed GBS infections in infants under 90 days old; and evaluating vaccine confidence among pregnant women and key community stakeholders. The project will develop tools and communication strategies to increase vaccine acceptance and participation in trials, strengthening healthcare systems for future vaccine delivery. Participants will include pregnant women, infants with confirmed GBS infections, and community stakeholders across the four countries. Researchers will collect and analyze health data, monitor infection rates, and assess attitudes toward vaccination. The study will track outcomes such as pregnancy and infant health, infection incidence, and vaccine confidence over multiple years, supporting ongoing safety monitoring and preparation for vaccine rollout through a coordinated network of maternal vaccine trial sites.

Researchers are evaluating the safety and effectiveness of the RTS,S/AS01 malaria vaccine through case-control studies embedded in the Malaria Vaccine Pilot Evaluation (MVPE) program conducted in Ghana, Kenya, and Malawi. This research focuses on measuring vaccine safety with attention to cerebral malaria, meningitis, and severe malaria, as well as assessing the vaccine's impact on all-cause mortality in boys and girls. The study also aims to support the use of case-control methods by immunization and malaria control programs. The study includes two main case-control components: one for clinical outcomes and one for mortality outcomes. Children aged 6 months to 59 months living in areas where the malaria vaccine is being implemented are enrolled as cases and controls. For each case identified through sentinel hospital surveillance or mortality verbal autopsies, four neighborhood controls are selected and interviewed. Data collection involves administering questionnaires at participants' homes to gather clinical and demographic information. The case-control studies will run for 45 months, recruiting thousands of cases and controls to provide strong statistical power for detecting differences in safety and mortality outcomes. Participants and their caregivers will be involved in consenting and providing information during home visits. The study collects data on diagnoses of meningitis, severe malaria, cerebral malaria, and death by gender over an average of one year. Researchers track and compare these outcomes between vaccinated and unvaccinated children using the case-control design. This approach allows monitoring vaccine safety and effectiveness while building local capacity for such evaluations.

Researchers are evaluating new drug regimens for treating adults with drug-susceptible pulmonary tuberculosis (TB) in a Phase 2 adaptive, randomized, controlled, open-label trial. The study aims to determine if these novel treatments provide better early effectiveness compared to the standard combination of isoniazid, rifampicin, pyrazinamide, and ethambutol. The safety and tolerability of these regimens will also be assessed over an 8-week treatment period. Participants will receive one of several drug combinations, including standard therapy with isoniazid, rifampicin, pyrazinamide, and ethambutol, or experimental regimens containing drugs like bedaquiline, pretomanid, linezolid, TBI-223, and sutezolid. Dosing varies by drug, with most taken orally once daily, often with meals. The initial 8 weeks constitute the study treatment phase, followed by an 18-week continuation phase of standard care, making the total treatment duration 26 weeks. Throughout the study, participants will undergo regular assessments, including sputum cultures to measure bacterial growth rates during the first 6 weeks and monitoring for any serious side effects by week 8. Laboratory tests, chest x-rays, and performance scores will be used to evaluate health status. Participants will be followed for a total of 52 weeks, ensuring safety and treatment effectiveness are closely monitored.