Swansea

Researchers are evaluating two different methods of pacing the heart in patients with slow heart rates (bradycardia). This multi-center randomized controlled trial, called PROTECT-HF, aims to compare the standard right ventricular pacing approach with a newer physiological pacing technique, which includes His bundle and left bundle area pacing. The study will enroll 2600 patients to assess differences in outcomes related to heart function and survival. Participants will be randomly assigned to receive either right ventricular pacing or physiological pacing through pacemaker implantation. The physiological pacing method may involve His bundle pacing or left bundle pacing, with biventricular pacing used if these are not possible. Both treatments will be performed at participating centers, with patients and outcome assessors blinded to the treatment allocation. A subgroup of 500 patients will also take part in an optional echocardiographic sub-study to observe heart changes over 24 months. During the study, participants will be monitored from the time of consent for up to 78 months. Evaluations will occur at the start and every six months afterward to track mortality and heart failure-related health events. Researchers will gather data on heart function, treatment effects, and safety. The main analysis will consider all patients as originally assigned, and additional analysis will assess those who received the assigned treatment.

Researchers are investigating treatments for women with recurrent endometrial cancer that expresses different levels of the HER2 protein. The study has two groups based on the tumor's HER2 score: Cohort 1 includes patients with HER2 IHC 1+ or 2+ who have previously received immune checkpoint inhibitors and platinum-based chemotherapy, while Cohort 2 includes patients with HER2 IHC 3+. The purpose is to compare the effectiveness and safety of the investigational drug BNT323 (also called DB-1303) against chemotherapy in Cohort 1 and to evaluate BNT323 alone in Cohort 2. The study also looks at how the drug affects the immune system, the body's handling of the drug, quality of life, and potential side effects. Participants in Cohort 1 are randomly assigned to receive either BNT323 via intravenous infusion or a chemotherapy drug chosen by the investigator (doxorubicin, paclitaxel, or docetaxel if paclitaxel is unsuitable). Treatment continues until the cancer progresses, unacceptable side effects occur, or the participant withdraws consent. Those in Cohort 2 receive BNT323 alone until disease progression or other discontinuation criteria are met. The study includes a screening period, a treatment period expected to last about six months, followed by safety monitoring, efficacy follow-up, and long-term survival follow-up lasting up to approximately 53 months. During the study, participants undergo regular assessments including imaging scans to measure tumor response by RECIST criteria, safety monitoring for adverse effects, and evaluations of quality of life. Researchers also study the pharmacokinetics of BNT323 and the immune response. The main outcomes measured are progression-free survival in Cohort 1 and objective response rate in Cohort 2. Safety follow-up ensures ongoing monitoring after treatment to evaluate longer-term effects and participant wellbeing.

Researchers are investigating the effectiveness, safety, and tolerability of combining baxdrostat with dapagliflozin compared to dapagliflozin alone in people with chronic kidney disease (CKD) and high blood pressure. This Phase III, international, multicenter, double-blind, placebo-controlled study aims to see if this combination reduces risks such as significant kidney function decline, kidney failure, heart failure events, or cardiovascular death. The study includes a 4-week run-in period where participants not previously treated with SGLT2 inhibitors receive dapagliflozin alone. After this, participants are randomly assigned to receive either baxdrostat plus dapagliflozin or placebo plus dapagliflozin in a double-blinded manner. Study visits occur frequently initially (at 2, 4, 8, 16, 34, and 52 weeks after randomization) and then approximately every 4 months. If participants stop the blinded treatment early, they continue dapagliflozin alone unless specific criteria require its discontinuation. Participants will undergo regular assessments including blood pressure monitoring and laboratory tests related to kidney function and cardiovascular health. The primary outcome measures the reduction in risk of major kidney and heart events over up to 37 months. Even if participants stop the study treatment, they will continue follow-up visits and data collection to ensure comprehensive safety and efficacy evaluation throughout the study duration.

This research aims to evaluate the effectiveness and safety of two different dose schedules of pegozafermin compared to a placebo in adults with metabolic dysfunction-associated steatohepatitis (MASH) who have liver fibrosis at stage F2 or F3. This phase 3 study focuses on improving liver fibrosis and steatohepatitis in this patient group, which involves chronic liver disease associated with metabolic dysfunction. Participants will receive either pegozafermin or a placebo through subcutaneous injections. The study compares two doses of pegozafermin to assess their impact on liver fibrosis and steatohepatitis. The treatment period lasts up to 52 weeks, with outcomes measured at this time point. During the study, participants will be monitored for improvements in liver fibrosis and resolution of steatohepatitis without worsening fibrosis by week 52. Researchers will also track the time until any disease progression occurs, up to 5 years. Throughout the trial, safety and efficacy will be carefully assessed through clinical evaluations and laboratory tests to ensure participant well-being.

Researchers are evaluating the effectiveness and safety of pirtobrutinib in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The study focuses on two parts: Part 1 tests three different doses of pirtobrutinib in participants who have had 1 to 3 prior treatments, including a covalent Bruton tyrosine kinase (BTK) inhibitor. Part 2 evaluates pirtobrutinib alone in participants who have not received prior treatment but have a specific genetic deletion called 17p. This is a phase 2, open-label, randomized study. Pirtobrutinib is given orally to participants in both study parts. Participants in Part 1 receive one of three dose levels, while those in Part 2 receive pirtobrutinib monotherapy. Part 1 participation lasts about 3 years, and Part 2 participation can last up to 2 years. The study compares the effects of different doses and treatment histories to better understand pirtobrutinib’s impact on CLL/SLL. Throughout the study, researchers monitor participants' overall response to treatment from the start up to 3 years. They assess safety and side effects, and participants are required to be able to swallow oral medication and have a performance status that allows them to participate. The study includes regular evaluations to determine how well the treatment controls the disease and to track any adverse events over the course of the study periods.

Researchers are evaluating the effectiveness and safety of pirtobrutinib (LOXO-305) compared to ibrutinib in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The study includes participants who may have had prior treatment as well as treatment-nave participants with a specific genetic deletion (17p deletion). The study is a Phase 3, open-label, randomized trial designed to assess these treatments in different patient groups over varying durations. Participants receive either oral pirtobrutinib or oral ibrutinib. Part 1 compares these two drugs in participants with or without prior therapy, and participation can last up to six years. Part 2 focuses on pirtobrutinib alone in treatment-nave participants with 17p deletions, with participation lasting up to two years. The study carefully monitors responses to treatment, including complete and partial remissions. Throughout the study, participants undergo regular assessments to track their response to therapy, including measuring overall response rates from the start of treatment until disease progression or new treatments begin. Safety and organ function are monitored, and laboratory tests help evaluate blood counts and kidney function. The study aims to provide detailed information on how well the treatments work and their safety over the long term.

Researchers are evaluating the safety, how the body processes the drug, how the drug affects the body, and the effectiveness of RO7268489 as an added treatment to ocrelizumab in adults with progressive multiple sclerosis (PMS). This phase II study focuses on people aged 18 to 60 with PMS who meet specific criteria, aiming to understand the impact of adding RO7268489 to their existing ocrelizumab therapy. After the main double-blind phase, an open-label extension may allow some participants to receive RO7268489 openly. Participants will receive either RO7268489, ocrelizumab, or a placebo according to a set schedule during the trial. RO7268489 and ocrelizumab are given as drugs, with the placebo group serving as a comparison. Following the double-blind period, eligible participants can join an open-label phase to receive RO7268489. Treatment plans and schedules are carefully followed as outlined in the study arms. Throughout the study, researchers will monitor participants for the time until the first confirmed worsening of disability lasting at least 12 weeks, over approximately 110 weeks. Participants will undergo regular assessments to track disease progression and safety. The study includes careful screening and ongoing evaluations to ensure participant health and to measure the effects of the treatments over time.

Researchers are studying Spinal Muscular Atrophy (SMA), a genetic motor neuron disease that affects both infants and adults. This research focuses on understanding how current standards of care and new treatments impact the natural progression of SMA in adults. The study is supported by The Newcastle upon Tyne Hospitals NHS Foundation Trust and funded by Biogen and Roche, involving collaboration with international SMA networks to improve patient care and future research. The study collects data on adults with SMA who may be receiving treatments such as Risdiplam and Nusinersen. These drugs are among the therapies available in the UK, with Zolgensma being the only fully approved drug and others accessible through Managed Access Agreements. The research builds on previous efforts in pediatric SMA studies and aims to standardize data collection across sites to better track long-term treatment effects. Participants will undergo various assessments every six months, including motor milestone evaluations, upper limb function tests, walking tests, and functional motor scales. These measures help monitor disease progression and treatment impact over time. The study also involves collecting information on patient health and treatment experiences to inform clinical decisions. Participation requires informed consent, with ongoing data collection throughout the study period.

Severe diabetic macular oedema (DMO) is a condition where fluid builds up in the macula, the central part of the retina responsible for detailed vision, leading to sight loss. This trial studies people over 18 years old with type 1 or type 2 diabetes who have severe DMO, defined by a thickened macula (400 microns or more). Researchers are comparing the current standard treatment of anti-VEGF eye injections alone to a new approach where patients start with anti-VEGF injections and switch to subthreshold micropulse laser (SML) treatment once the macula thickness decreases below 400 microns. Participants will be randomly assigned to receive either ongoing anti-VEGF injections or to switch to SML treatment after initial anti-VEGF therapy. Anti-VEGFs such as ranibizumab, aflibercept, faricimab, and brolucizumab are given as monthly injections at first, then every 1-3 months. The SML procedure, which does not damage the macula, will be applied based on the trial guidelines once the macula is less than 400 microns thick. This study aims to see if the combined treatment is as effective and more cost-efficient than anti-VEGF injections alone. Participants will attend regular clinic visits for eye exams including optical coherence tomography (OCT) scans to measure macula thickness and assessments of visual acuity over 104 weeks after randomization. Researchers will monitor best-corrected visual acuity, side effects, participant experience, and cost-effectiveness. The trial includes follow-up for two years with safety monitoring and evaluation of how this approach might be adopted in routine care. The study is conducted at multiple hospital eye services across the UK.

Researchers are evaluating whether ziltivekimab can help people who were hospitalized due to a heart attack by potentially reducing the development of heart disease and preventing new heart attacks or strokes. This Phase 3 study compares ziltivekimab with a placebo, which is a dummy medicine that has no effect on the body. Both treatments are given by chance, with equal likelihood for participants to receive either ziltivekimab or placebo. Participants will inject the study medicine once a month under the skin in the stomach, thigh, or upper arm. Ziltivekimab is given as an initial loading dose followed by monthly maintenance doses. The placebo group receives a matching injection schedule. The study duration is about two years. During the study, researchers will monitor participants for the time until the first serious heart-related event, including cardiovascular death, non-fatal heart attack, or non-fatal stroke. Participants will be closely observed from the start of randomization up to 25 months. The study includes regular follow-ups to assess safety and effectiveness of the treatments throughout this period.