Manaus

Researchers are evaluating new medicines to prevent HIV-1 Human Immunodeficiency Virus Type 1 infection. This Phase 3 clinical study aims to determine if taking the drug MK-8527 once a month can prevent HIV-1 infection as well as or better than the standard daily pre-exposure prophylaxis PrEP. The study also assesses the safety and tolerance of MK-8527 in participants. Participants are randomly assigned to one of two groups. One group receives 11 mg of MK-8527 once monthly along with a daily placebo pill matching FTCTDF. The other group receives a daily dose of FTC245 mg TDF and a monthly placebo matching MK-8527. This treatment period lasts for approximately two years, followed by an additional 28-day period where all participants receive open-label FTCTDF daily. During the study, participants will undergo regular monitoring to check for HIV-1 infection and any adverse events. Researchers will track the number of participants who acquire HIV-1, experience side effects, or stop treatment due to side effects over the two-year period. Safety and adherence assessments will be conducted to evaluate the study treatments. The total participation time includes the two-year treatment phase plus the 28-day follow-up with open-label FTCTDF.

Researchers are evaluating a revised weight-based dose of tafenoquine target dose 7.5mgkg to treat patients with vivax malaria. This Phase 3 trial aims to determine if this revised regimen is not worse than a high dose of primaquine given over seven days and if it is better than the standard fixed dose of tafenoquine. The study also looks at how well patients tolerate the revised dose and whether it is practical to use. Participants will be randomly assigned to one of three groups. One group will receive a single weight-based oral dose of tafenoquine along with schizontocidal treatment. Another group will receive a single fixed oral dose of 300mg tafenoquine plus schizontocidal treatment. The third group will receive schizontocidal treatment plus a high dose of primaquine given orally over seven days. The trial will monitor safety and effectiveness over several months. During the study, participants will be followed for six months. Researchers will assess the occurrence of vivax parasitaemia at 4 and 6 months as the main outcome. Other measurements include symptomatic vivax parasitaemia, anemia incidence at different time points, hemoglobin changes, adverse events, and methemoglobin levels. Participants must provide informed consent and live in the study area to allow regular follow-up and monitoring throughout the trial.

Researchers are evaluating the efficacy and safety of iza-bren, a bi-specific antibody-drug conjugate targeting EGFR and HER3 with a chemotherapy payload, compared to treatment chosen by physicians including paclitaxel, nab-paclitaxel, carboplatin plus gemcitabine, and capecitabine for patients with first-line metastatic triple-negative breast cancer TNBC or low estrogen receptor ER-low, HER2-negative breast cancer who cannot receive anti-PDL1 or endocrine therapies. This study includes adults with locally advanced, recurrent inoperable, or metastatic disease who meet specific eligibility criteria. Participants are randomly assigned to receive iza-bren or one of the physicians choice chemotherapy regimens. The treatments are given at specified doses on scheduled days. The study includes two phases Phase 2 to determine the recommended dose of iza-bren and Phase 3 to compare progression-free survival and other outcomes. The study will last several years, with follow-up extending up to approximately 47 months after randomization. During the study, participants will undergo regular assessments including imaging scans to measure tumor response, laboratory tests, and monitoring for adverse events. Quality of life questionnaires will also be completed. Researchers will track progression-free survival, overall survival, treatment-related side effects, tumor size changes, and patient-reported outcomes to evaluate the treatments. The total participation duration may extend up to several years depending on treatment response and follow-up requirements.

Researchers are evaluating the effects of EYU688, an oral drug, compared with a placebo in patients with dengue fever. The study aims to understand how EYU688 influences dengue viral load, fever clearance time, and clinical symptoms. This randomized, participant- and investigator-blinded, placebo-controlled trial includes two patient groups based on different pharmacokinetic sampling schedules. Participants will receive either EYU688 or a matching placebo orally. The study runs two cohorts in parallel one with intensive pharmacokinetic sampling and another with sparse sampling. Treatment and assessments occur from the start of dosing through Day 15, with additional safety monitoring up to Day 35. The study measures drug concentration levels and viral load changes over time. Throughout the study, participants will undergo evaluations including viral load tests, fever monitoring, blood tests for blood cells and liver enzymes, and assessments for dengue severity. Safety and adverse events are recorded up to Day 35. The primary outcome is viral load reduction at 48 hours after treatment begins. Participation lasts until study completion, expected by July 2027.

Researchers are investigating whether patients with locally advanced cervical cancer who still have detectable cell-free human papillomavirus DNA cfHPV-DNA in their plasma after standard treatment may benefit from additional chemotherapy. This trial is a prospective, randomized, multicenter clinical study designed to evaluate adjuvant chemotherapy based on this biomarker. The study focuses on patients who have undergone chemoradiotherapy and have persistent cfHPV-DNA, as this may indicate ongoing disease activity. Participants first receive standard treatment with concomitant chemoradiotherapy, including doses of radiation and weekly cisplatin. Four weeks after completing this treatment, a blood test is conducted to detect cfHPV-DNA in plasma. Patients with positive cfHPV-DNA results are randomly assigned to either receive two additional cycles of adjuvant chemotherapy with cisplatin and gemcitabine or to be monitored without further chemotherapy. Patients in both groups undergo regular follow-up every four months, including plasma cfHPV-DNA testing, CT scans of the chest, MRI scans of the abdomen and pelvis, and clinical and gynecological exams. During the study, participants are closely monitored for progression-free survival, overall survival, treatment response, quality of life, and any toxic effects of treatment. Follow-up assessments occur at regular intervals from 7 to 120 days after treatment. The total duration of participant involvement varies based on follow-up schedules. The study uses a single-blind design and randomized allocation to ensure scientific rigor while maintaining patient safety throughout the trial period.

Researchers are evaluating the effect of muvalaplin in lowering cardiovascular risks among adults with elevated lipoproteina who either have atherosclerotic cardiovascular disease or are at risk of a first heart attack or stroke. This phase 3, randomized, double-blind study aims to investigate whether muvalaplin can reduce major adverse cardiovascular events compared to placebo in this high-risk population. Participants are randomly assigned to receive either muvalaplin or a placebo, both given orally. The study is designed with parallel groups and will last about 5.25 years, during which the occurrence of cardiovascular events and changes in lipoproteina levels will be closely monitored. Throughout the study, participants will undergo regular assessments including measurement of lipoproteina levels, monitoring of cardiovascular events such as heart attacks or strokes, and evaluation of healthcare resource use. The primary outcome is the time to first major adverse cardiac event, tracked from baseline until the study ends. Safety and pharmacokinetics of muvalaplin will also be evaluated during the trial period.

Researchers are evaluating the safety, effectiveness, and tolerability of a dual therapy regimen of dolutegravir plus lamivudine given either twice daily or as a combination in the morning plus dolutegravir in the evening, compared to the standard three-drug antiretroviral therapy ART in people living with HIV-1 who have not previously received ART and are also being treated for tuberculosis TB with rifampin-based therapy. This Phase IIIb international, multicenter, randomized trial aims to find better treatment options for patients co-infected with HIV and TB, conditions that commonly occur together and require concurrent treatment to improve survival. Participants will be randomly assigned to one of three treatment groups Arm 1 receives the fixed-dose combination tablet of dolutegravir 50 mg and lamivudine 300 mg twice daily during TB therapy and for two weeks after, then once daily through week 52. Arm 2 receives the same tablet once daily in the morning plus dolutegravir 50 mg at night during TB treatment and for two weeks after, followed by once daily dosing of the combination tablet through week 52. Arm 3 receives the local standard care of dolutegravir 50 mg plus tenofovir disoproxil fumaratelamivudine once daily during TB therapy and for two weeks after, then continuing the same once daily through week 52. During the study, participants will be monitored for HIV viral load suppression at 28 weeks and 48 weeks, changes in CD4 cell counts, and drug concentration levels over two years. Safety will be assessed by tracking adverse events. The trial includes laboratory tests and clinical assessments to evaluate efficacy and tolerability, with follow-up extending to 52 weeks for treatment and two years for safety monitoring. This comprehensive evaluation helps understand how well the dual therapy works compared to standard treatment in this population.

Researchers are evaluating the effects of vicadrostat combined with empagliflozin in adults who have type 2 diabetes, high blood pressure, and cardiovascular disease but no history of heart failure. The study aims to assess whether this combination can help reduce cardiovascular risks compared to a placebo with empagliflozin. This Phase III trial involves adults with these conditions who are already receiving treatment for them. Participants are randomly assigned to one of two groups. One group takes vicadrostat and empagliflozin tablets daily, while the other group takes placebo tablets that look like vicadrostat but have no active medicine, alongside empagliflozin. Treatment lasts from two and a half years up to four years and three months. All participants continue their usual medications for diabetes, blood pressure, and heart disease during the study. Throughout the study, lasting up to four years and three months, participants visit the study site regularly for health checks and blood samples. Doctors monitor cardiovascular events and any side effects experienced. The main outcome measured is the time until the first cardiovascular death or heart failure event. Other health indicators like blood pressure and kidney function are also tracked to understand the effects of the treatment combination.

Researchers are evaluating how well long-acting lenacapavir works to prevent HIV infection in people at higher risk in Brazil. The study aims to assess safety, continued use over time, and participant preference compared to daily oral pre-exposure prophylaxis PrEP. It focuses on how many participants get HIV while using lenacapavir, its safety in real-world health settings, and factors affecting ongoing prevention use. Participants can choose between two prevention options injections of long-acting lenacapavir under the skin every six months or daily oral PrEP pills containing tenofovir disoproxil fumarate and emtricitabine. Those choosing lenacapavir receive an oral loading dose followed by subcutaneous injections at enrollment and every six months, up to four injections during follow-up. Those choosing oral PrEP take daily pills with regular medication dispensing and follow-up visits. Both groups receive prevention counseling, regular HIV testing, and screening for sexually transmitted infections and viral hepatitis. Participants will visit clinics regularly for HIV testing, health checkups, and safety monitoring. They will answer questions about their health, medication use, and experiences, while researchers evaluate adherence, injection site reactions, and adverse events. The study will track persistence on lenacapavir over 24 months and time to discontinuation. This research will help health services understand how to offer and support long-acting HIV prevention in Brazil, with follow-up lasting up to two years.

Cancer is a challenging and widespread disease that often leads to uncontrolled pain and reduced quality of life for many patients who lack access to specialized care. This research investigates how meditation delivered through immersive virtual reality can help cancer patients manage pain and improve their well-being. The study includes a randomized controlled trial to evaluate this meditation method compared to other approaches. Participants are divided into three groups an experimental group using a 7-minute immersive virtual reality mindfulness meditation video with VR glasses and a smartwatch, an active control group viewing a similar meditation video on a cellphone with a smartwatch, and a passive control group performing guided breathing exercises with audio and a smartwatch. All groups practice meditation at home three times a week for four weeks, supported by SMS reminders and self-reporting forms. Throughout the study, participants complete questionnaires on quality of life, psychological health, pain, and symptoms at three time points baseline, after four weeks, and after eight weeks. The smartwatch tracks heart rate, blood oxygen, movement, and distress levels. The main outcomes measured include pain and quality of life over six months, with additional assessments of anxiety, depression, symptoms, and distress. The total study duration for each participant is about two months, with ongoing monitoring using mobile apps and wearable devices.