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Researchers are evaluating two different pacing methods for patients with slow heart rates, called bradycardia. This study compares the common right ventricular pacing approach with a newer physiological pacing method that includes His bundle and left bundle area pacing. The trial aims to better understand how these pacing techniques affect patient outcomes, including mortality and heart failure morbidity, in a large group of 2600 patients. Participants will receive a pacemaker implant and be randomly assigned to either right ventricular pacing or physiological pacing. The physiological pacing may involve His bundle pacing or left bundle pacing, but if these are not successful, biventricular pacing will be used. A subgroup of 500 participants will take part in an optional echocardiographic sub-study to assess heart function changes over a 24-month period. Throughout the study, patients will be assessed at baseline and every six months after randomization, with follow-up lasting up to 78 months. Researchers will monitor outcomes such as mortality, heart failure events, device-related safety issues, patient quality of life, symptoms, and pacemaker-derived data like arrhythmias and activity levels. The echocardiographic sub-study will measure specific heart function changes to understand pacing-induced cardiomyopathy. Participants involvement includes implantation, regular follow-up visits, questionnaires, and optional imaging assessments.

This research aims to evaluate whether creating dedicated HIV teams in hospitals across ten European countries can increase HIV testing rates among patients showing signs of HIV-related conditions. The study uses a stepped-wedge design, where hospitals switch from routine care to the new intervention in sequence. This approach compares outcomes before and after the teams are in place, helping to understand the impact of the intervention across various locations and medical specialties. The intervention involves establishing local HIV teams led by specialists and supported by nurses and data experts. These teams identify patients needing HIV tests through electronic health records, provide feedback to doctors to encourage testing, offer education to healthcare staff about HIV, reduce stigma, and improve connections to prevention and care services. This program integrates smoothly into regular hospital routines and aims to close gaps in HIV diagnosis. Participants HIV testing rates will be monitored by reviewing records before and after the intervention. Researchers will also assess new HIV diagnoses, changes in testing patterns by country and specialty, and healthcare professionals knowledge and attitudes toward HIV. The study includes ongoing evaluation of how well the teams operate, resource use, and cost-effectiveness. Data collection extends up to several years to observe long-term effects, with continuous monitoring of care access and prevention services.

Researchers are investigating CGT9486, also known as bezuclastinib, in an open-label Phase 2 study for patients with Advanced Systemic Mastocytosis AdvSM. This includes those diagnosed with Aggressive Systemic Mastocytosis ASM, Systemic Mastocytosis with an Associated Hematologic Neoplasm SM-AHN, and Mast Cell Leukemia MCL. The study aims to evaluate the safety, effectiveness, pharmacokinetics, and pharmacodynamics of bezuclastinib in this patient population. Participants will receive bezuclastinib tablets orally, taken continuously in 28-day cycles. The study is divided into two parts Part I focuses on identifying effective and tolerable dosing exposures over 18 months, while Part II evaluates the drugs efficacy by measuring objective response rates and confirming the exposure-response relationship, also over 18 months. Additional assessments include effects on mutation allele burden, serum tryptase levels, histopathologic changes, spleen and liver volume, and safety monitoring. During the study, participants will undergo various clinical evaluations, including laboratory tests, imaging to monitor organ size changes, and assessments of disease response and progression. Researchers will track adverse events and pharmacokinetic profiles throughout the 18 months. The study involves continuous monitoring of participants to understand the treatments impact on survival and disease progression over this period.

Researchers are evaluating the safety and effectiveness of elenestinib BLU-263 combined with symptom directed therapy SDT compared to placebo plus SDT in adults with indolent systemic mastocytosis ISM whose symptoms are not well controlled by SDT alone. This randomized, double-blind, placebo-controlled Phase 23 study includes multiple parts to assess different doses and durations of elenestinib treatment, including an open-label extension for participants finishing earlier phases. The study also enrolls participants who have previously received an approved selective KIT inhibitor and includes pharmacokinetic groups. Participants receive oral elenestinib or placebo once daily alongside SDT, which is personalized based on individual symptom management needs. Part 1 focuses on short-term treatment lasting up to 12 weeks, while Part 2 extends treatment to approximately 48 weeks. Part 3 and other parts allow treatment for up to about 5 years. The study monitors participants through these phases to evaluate how elenestinib affects symptoms, disease markers, and safety over time. During the study, participants undergo regular assessments of symptoms using the ISM-Symptom Assessment Form ISM-SAF, laboratory tests including serum tryptase and KIT D816V allele levels, bone marrow evaluations, and quality of life measures. Researchers track adverse events and changes in disease-related factors at various points up to 5 years. This thorough monitoring helps measure treatment effects and safety over both short and long-term periods, with total participation lasting several years depending on the study part.

Researchers are evaluating the combination of CGT9486 and sunitinib compared to sunitinib alone in patients with locally advanced, unresectable, or metastatic Gastrointestinal Stromal Tumors GIST. This Phase 3, open-label international trial involves multiple parts, including dose confirmation, drug interaction assessments, and efficacy comparisons. The study also includes substudies focusing on drug-drug interaction potential and first-line treatment in patients with specific genetic mutations KIT exon 9. Approximately 482 patients will participate across these parts.

Researchers are working to create and use a comprehensive database focused on intracranial aneurysms IA. This project collects and studies clinical history, imaging data, biological samples, and other information to understand factors linked to the formation and rupture of aneurysms. They aim to identify genetic, environmental, and anatomical markers, as well as evaluate outcomes from different treatment strategies and improve patient care protocols. Participants include patients with diagnosed aneurysms, both ruptured and unruptured, family members of affected individuals, and healthy volunteers. Data collected involves detailed clinical records, imaging scans like MRI angiography and CT angiography, and various biological samples such as blood, cerebrospinal fluid, saliva, and stool. Consent covers access to medical records, use of biological samples, and potential future research uses including genetic analyses. During the study, participants provide health and lifestyle information, imaging data, and biological samples. Researchers will monitor multiple long-term outcomes including disease progression, life expectancy, quality of life, neurological and cognitive status, and treatment effects over periods up to 20 years. Data confidentiality is maintained, and participants can withdraw at any time without affecting their medical care. The study aims to validate disease models and support advances in aneurysm management and research.

Researchers are evaluating the effectiveness of delgocitinib cream 20 mgg applied twice daily compared to a cream vehicle in treating adults with mild to severe palmoplantar pustulosis PPP. This trial is a phase 2a, double-blind study focusing on this skin condition characterized by pustules on the palms and soles. The main goal is to see how well delgocitinib cream improves symptoms over a 16-week treatment period. Participants will be randomly assigned to one of two groups one group will apply delgocitinib cream twice a day for 16 weeks, while the other group will use a matching vehicle cream twice daily for the same duration. The study includes a total of approximately 18 weeks for each participant, involving around 9 visits. The trial compares the active cream to the placebo cream to assess efficacy and safety. During the study, participants will attend scheduled visits to monitor their condition and collect data on skin symptoms, pustule counts, and quality of life measures. Researchers will assess the improvement in PPP severity using specific scales such as the PPP Area and Severity Index PPPASI. Safety is monitored through reports of any treatment-emergent side effects. Overall participation lasts about 18 weeks, including screening and treatment phases.

Researchers are evaluating how well MSP-2020, a study drug, attaches to serotonin type 2A receptors in the brain of healthy male adults. This Phase 1 study aims to understand the drugs presence in the blood, how long it stays, and its safety profile. The study is conducted by Otsuka Pharmaceutical Development & Commercialization, Inc. and focuses on healthy volunteers aged 23 to 55 years. Participants will receive a single oral dose of MSP-2020 on Day 1. The study uses positron emission tomography PET scans to measure receptor occupancy and drug binding. Blood samples will be collected up to Day 2 to analyze the drugs concentration, peak levels, half-life, and metabolite presence. Safety will be monitored through assessments including vital signs, ECG, laboratory tests, and neurological exams. During the study, participants will stay in a clinical research unit for up to 4 days for observation and assessments. Researchers will monitor adverse events and changes in health status up to Day 15. The primary outcomes focus on drug binding in the brain and pharmacokinetics, while secondary outcomes include safety measures and changes in relevant clinical scales. The total participation time includes dosing, imaging, blood sampling, and safety follow-up.

Researchers are evaluating if combining the medicines calderasib and subcutaneous pembrolizumab can more effectively treat people with non-small cell lung cancer NSCLC that has a KRAS G12C mutation. The study aims to find out whether patients receiving calderasib with pembrolizumab live longer without their cancer growing or spreading compared to those receiving pembrolizumab with chemotherapy. This is a Phase 3 clinical trial focusing on first-line treatment for advanced or metastatic nonsquamous NSCLC. Participants are assigned to one of two groups. One group receives subcutaneous pembrolizumab plus berahyaluronidase alfa every 6 weeks for up to 18 cycles about 2 years along with oral calderasib until treatment discontinuation criteria are met. The other group receives the same pembrolizumab and berahyaluronidase alfa regimen plus chemotherapy with pemetrexed and either carboplatin or cisplatin infusions during the early cycles. Treatment continues based on individual response and tolerability. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess progression-free survival, overall survival, response rates, and quality of life using questionnaires and symptom scores over several years. Safety will be monitored through adverse event reporting. The trial lasts up to about 7 years with ongoing evaluation of health outcomes and side effects to understand the impact of these treatment combinations.

Researchers are evaluating calderasib alone or combined with cetuximab to treat people with advanced solid tumors that have the KRAS G12C mutation, excluding colorectal cancer. This study aims to measure how many participants experience tumor shrinkage or disappearance and compare the responses between the two treatments. It is a phase 2, open-label trial focused on treatment safety and tolerability. Participants will receive calderasib orally with no set limit on treatment cycles. Some participants will also receive cetuximab via intravenous infusion every two weeks. Treatment continues until criteria for stopping the study intervention are met. The trial uses a randomized, parallel design to compare the two experimental arms. Throughout the study, participants will be monitored for tumor response, adverse events, and treatment discontinuations related to side effects. Researchers will also assess progression-free survival, duration of response, and overall survival up to about 76 months. The trial lasts until April 2032, with ongoing safety and efficacy evaluations during this period.