Bournemouth

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 gather long-term safety and effectiveness information for people treated with ibrutinib, a medicine taken by mouth that blocks a specific enzyme called brutons tyrosine kinase. The study focuses on participants who previously took part in ibrutinib studies that have finished and are still receiving ibrutinib treatment, continuing to benefit from it. It is an open-label study, meaning both participants and researchers know the treatment being given. Participants will continue taking ibrutinib capsules daily at the dose they were given in their prior study until the doctor decides the treatment is no longer helpful due to disease progression or side effects, the participant chooses to stop, other treatment options become available, or the study ends. Safety will be monitored throughout, and effectiveness data may be combined with previous study results. No formal testing of hypotheses is planned in this extension. During the study, participants will be regularly monitored for safety and disease status. The main outcome is the number of participants experiencing side effects within 30 days after the last ibrutinib dose or before starting another cancer therapy. Participants may continue treatment until alternative access to ibrutinib is arranged or the study ends, which is planned for December 2029. Researchers will collect ongoing data to understand the long-term effects of ibrutinib treatment.

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study. This trial focuses on patients with established atherosclerotic cardiovascular disease ASCVD or those at high risk for a first ASCVD event. The study aims to assess how AZD0780 compares to placebo in reducing the risk of major adverse cardiovascular events, also known as MACE-PLUS, over the course of the trial. Participants are randomly assigned to receive either oral AZD0780 once daily or a matching placebo once daily. The study continues until a primary analysis censoring date, which may be up to approximately 54 months from randomization. After this, a study closure visit will be conducted as the final visit for each participant. During the study, participants will be regularly monitored for cardiovascular events including heart attacks, strokes, urgent coronary revascularizations, and other related outcomes. Researchers will track the time to first occurrence of these events as the primary outcome. Safety and other secondary outcomes like all-cause mortality will also be assessed. The total participation time can last up to about 54 months, with ongoing evaluations throughout this period.

Researchers are studying patients with cirrhosis caused by alcohol-related or metabolic dysfunction-associated steatotic liver disease MASLD. The trial aims to evaluate whether taking capsules containing faecal microbiota from healthy donors can reduce infections and mortality in these patients. This Phase 3 trial follows earlier research that showed faecal microbiota transplantation FMT delivered via endoscopy was safe and feasible, leading to the development of capsules for easier treatment administration. Participants will be randomly assigned to receive either encapsulated FMT or placebo capsules that look identical but contain no active treatment. They will take five capsules every three months over a total period of 21 months or until they develop an infection requiring hospital admission. This double-blind trial means neither participants nor study staff will know which treatment is given. The study will last up to 24 months including follow-up, monitoring effects on infection rates, liver health, immune system function, and antibiotic resistance. Throughout the trial, participants will be regularly assessed for infections, liver disease progression, hospital admissions, quality of life, mental health, alcohol use, and safety of FMT treatment. Laboratory tests will examine immune response and bacterial resistance. The primary outcome is the time until first infection needing hospital care. The study involves detailed monitoring and follow-up visits for up to two years to understand the treatments impact and safety in patients with cirrhosis.

Researchers are evaluating whether less frequent dosing of pembrolizumab after six months of standard treatment is safe and effective for patients with advanced non-small cell lung cancer NSCLC. Pembrolizumab, an immunotherapy targeting the PD-1 receptor, has improved outcomes in NSCLC, but current dosing every six weeks for up to two years may result in overtreatment. This UK phase III trial aims to find if reducing dose frequency can maintain effectiveness while improving quality of life and lowering costs. Participants who have received six months of pembrolizumab, with or without chemotherapy, and plan to continue treatment will be randomized to receive pembrolizumab intravenously every six weeks control or every twelve weeks initially. If the 12-week dosing is found to be not less effective, additional groups receiving doses every nine, fifteen, and eighteen weeks will be included. Patients who experience disease progression while on reduced frequency dosing can return to the standard six-week schedule. Throughout the study, participants will be monitored for overall survival at 18 months from randomization, along with other outcomes such as progression-free survival, response rate, duration of response, and adverse events over two years. The study involves regular hospital visits for treatment and assessments, and the results may lead to safer, more convenient treatment options for NSCLC patients. The total participation time varies depending on individual treatment and follow-up schedules.

Researchers are evaluating the efficacy and safety of BGB-16673 compared with the investigators choice of treatments in participants with chronic lymphocytic leukemia CLL or small lymphocytic lymphoma SLL who have previously been treated with both Bruton Tyrosine Kinase inhibitors BTKi and B-cell leukemialymphoma 2 protein inhibitors BCL2i. This study addresses the urgent need for new treatments to extend life and control symptoms such as enlarged lymph nodes, spleen, or liver, night sweats, weight loss, and fever in these patients. Participants will be randomly assigned to receive either BGB-16673 once daily or the investigators choice of treatment, which includes idelalisib plus rituximab for CLL only, bendamustine plus rituximab, or venetoclax plus rituximab retreatment. Treatments will continue until criteria for stopping treatment are met. This is a Phase 3, open-label, randomized study conducted globally with about 250 participants. During the study, participants will undergo regular assessments to monitor disease progression and response to treatment. Researchers will evaluate progression-free survival, overall survival, response rates, duration of response, and quality of life measures over approximately 24 to 36 months. Safety will be closely monitored by tracking treatment-emergent adverse events. Participants involvement includes receiving study medication, regular visits, and various evaluations to assess treatment effects and side effects.

Researchers are evaluating a combination therapy of finerenone plus empagliflozin compared to usual care in patients hospitalized with heart failure. This international, randomized, controlled, open-label trial aims to assess the effectiveness and safety of this early, intensive treatment approach in managing heart failure during and after hospitalization. Participants will either receive the combination of oral finerenone and empagliflozin or continue with usual care management. The study is designed to compare these two approaches to determine their impact on clinical outcomes. The trial includes a treatment period with these medications given alongside usual management during hospitalization and follow-up. During the study, participants will be monitored over six months for clinical benefits and safety outcomes such as serious adverse events and adverse events leading to discontinuation. Researchers will assess heart failure events, symptom changes using the Kansas City Cardiomyopathy Questionnaire, and time to death or heart failure events. Study visits and evaluations will track participant health and response to treatment over this period.

Researchers are evaluating the effectiveness and safety of combining sonrotoclax with either obinutuzumab or rituximab compared to venetoclax plus rituximab in adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma CLLSLL. This Phase 3 randomized study aims to understand which combination offers better progression-free survival and treatment outcomes in patients who have undergone prior therapies. The study has four treatment groups sonrotoclax combined with obinutuzumab, sonrotoclax combined with rituximab, sonrotoclax plus obinutuzumab with treatment guided by minimal residual disease evaluation, and venetoclax combined with rituximab. Sonrotoclax and venetoclax are given orally, while obinutuzumab and rituximab are administered intravenously. Participants receive these treatments according to their assigned group as part of this clinical research. Participants will be monitored for progression-free survival, overall survival, response rates, and minimal residual disease status over several months up to several years. Safety assessments include tracking treatment-emergent adverse events. Quality of life and symptom burden will be evaluated using questionnaires. The study involves regular visits for treatment administration and assessments, with follow-up extending up to 84 months to observe long-term outcomes.

Researchers are evaluating the effectiveness and safety of two fixed-duration treatment combinations for adults with previously untreated chronic lymphocytic leukemia CLL. The study compares sonrotoclax plus zanubrutinib with venetoclax plus acalabrutinib to determine which regimen may better manage this condition. This Phase 3 trial aims to provide insights into these oral therapies for CLL patients needing initial treatment. Participants will be randomly assigned to receive either sonrotoclax and zanubrutinib or venetoclax and acalabrutinib. Both treatment groups will follow a fixed duration of therapy, after which participants will be observed without active treatment. The study drugs are taken orally, and the treatment period is followed by a monitoring phase to evaluate ongoing health. During the study, participants will undergo evaluations including imaging tests to measure disease status and assessments of bone marrow and organ function. Researchers will track progression-free survival and minimal residual disease levels up to about 70 months. Other outcomes such as overall survival, response rates, adverse events, and quality of life will also be monitored. The total study duration extends until November 2031, offering long-term follow-up for participants.

Researchers are evaluating the combination of sonrotoclax plus zanubrutinib compared with zanubrutinib plus placebo in adults with relapsed or refractory mantle cell lymphoma MCL. This Phase 3 randomized, double-blind study aims to compare how well these treatments work and assess their safety in this patient population. The study is sponsored by BeOne Medicines and focuses on patients who have previously received 1 to 5 prior systemic therapies including anti-CD20 monoclonal antibody or chemoimmunotherapy. Participants will receive either sonrotoclax plus zanubrutinib or placebo plus zanubrutinib, both administered orally. The study has two groups one receiving the combination of sonrotoclax and zanubrutinib, and the other receiving zanubrutinib with placebo. Treatment continues as per protocol, and the study includes detailed assessments of response and safety over time. During the study, participants will be monitored for progression-free survival as the primary outcome, assessed by an independent review committee over approximately 41 months. Secondary outcomes include overall survival, response rates, duration of response, health-related quality of life, and adverse events up to around 58 months. Regular evaluations will be conducted to assess disease status, quality of life, and safety throughout the trial, which is planned to complete by 2032.