Chichester

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.

Researchers are evaluating the safety and effects of a new medicine called NNC0487-0111 in people who have Heart Failure with preserved Ejection Fraction HFpEF or Heart Failure with mildly reduced Ejection Fraction HFmrEF and excess body weight. This phase 3 clinical trial aims to find out if NNC0487-0111 is safe and effective for treating these conditions compared to a placebo. Participants have HFpEF or HFmrEF and a body mass index of 30 or above. The study is sponsored by Novo Nordisk AS and uses a randomized, quadruple-masked design. Participants will receive either NNC0487-0111 or a matching placebo by injection under the skin once a week. The NNC0487-0111 is given in increasing doses over time. The study is parallel in design, meaning participants are randomly assigned to one of the two groups and receive that treatment throughout the trial. This treatment period extends for up to about 165 weeks. The study evaluates the time to certain heart failure events, hospitalizations, cardiovascular deaths, and other major cardiovascular events. During the study, participants will be monitored regularly to assess heart failure outcomes and kidney function, as well as quality of life using questionnaires like the Kansas City Cardiomyopathy Questionnaire. Safety and effectiveness are assessed through hospital visits, heart failure event tracking, and blood tests including kidney function and blood sugar levels. The total participation spans over three years, with ongoing evaluations to measure the time to heart failure events and cardiovascular outcomes. Participants receive close medical monitoring throughout the study period.

This research aims to learn about the safety and effects of the study medicine PF-07328948 for adults with heart failure. The study evaluates whether PF-07328948 is safe and effective compared to a placebo in people who already take standard heart failure medicines including SGLT2 inhibitors. It is a phase 2 randomized, double-blind, placebo-controlled trial sponsored by Pfizer. Participants will take either placebo tablets or one of three doses of PF-07328948 tablets once daily by mouth for 36 weeks. The study includes four groups placebo, low dose, medium dose, and high dose of PF-07328948. Treatment lasts 36 weeks, followed by monitoring and assessments. Participants will be involved for about 48 weeks with 15 visits to the study clinic, of which 5 may be performed at home by phone and 10 in person. Researchers will assess clinical events, 6-minute walk test distance, and heart failure symptom scores at baseline and week 36. Safety will be monitored through adverse event reporting up to week 40. Various questionnaires and physical tests will track health status and treatment effects throughout the study.

This study evaluates the long-term safety and tolerability of pelacarsen TQJ230 in people with established cardiovascular disease and elevated Lipoproteina who completed a previous related study. It is an open-label extension trial, meaning all participants receive the study drug without placebo comparison. The trial is sponsored by Novartis Pharmaceuticals and focuses on continued treatment after the completion of the parent study. Participants receive monthly injections of pelacarsen 80 mg subcutaneously for up to 36 months during this extension phase. This phase is designed to provide access to the study drug after the initial trial and to monitor participants closely. The study does not involve randomization or blinding, and all enrolled participants receive the active drug. During the study, participants will undergo regular assessments including monitoring for adverse events and cardiovascular events, as well as measuring Lipoproteina levels at baseline and several time points over 36 months. Safety and tolerability will be closely tracked throughout the treatment period. The total duration of participation corresponds to the length of the extension phase, up to three years.

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.

The trial investigates the benefits and risks of an intensive weight loss intervention compared with bariatric surgery for adults with severe and complex obesity. The goal is to understand how these approaches compare and to guide future treatment options for people who currently have bariatric surgery as the only effective choice. This research is led by the Lighthouse Consortium on Obesity Management LightCOM and aims to inform care pathways for obesity treatment. The intensive weight loss intervention lasts two years and includes three phases an induction phase with total dietary replacements and behavioral support plus weight loss medication if needed a weight loss continuation phase with gradual reintroduction of healthy foods, physical activity, behavioral support, and medication as required and a maintenance phase with continued healthy diet, activity, and medication as needed, with return to induction if weight regain occurs. The comparator group receives bariatric surgery, either Roux-en-Y gastric bypass or sleeve gastrectomy. Participants will undergo assessments over 104 weeks including measures of metabolic syndrome MetS-Z, body weight, gait speed, and mental health scores. The study includes regular monitoring of diet, medication use, physical activity, and adherence. Safety and long-term outcomes are followed throughout the two-year study period to evaluate the effects of each intervention on obesity and related health aspects.

Researchers are evaluating the medicine pelacarsen TQJ230 compared to a placebo in adults with atherosclerotic cardiovascular disease ASCVD who have high levels of lipoproteina and are already receiving inclisiran treatment to lower their LDL cholesterol. This study is a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial with a parallel group design to assess the efficacy, safety, and tolerability of pelacarsen. Participants will be randomly assigned to receive either pelacarsen injections once a month for 12 months or placebo injections once a month for 6 months, followed by pelacarsen injections for the remaining 6 months during an open-label phase. All participants also receive background inclisiran treatment consisting of two initial loading doses three months apart, followed by doses every six months as per approved guidelines. During the study, participants will have regular visits and assessments including laboratory tests to measure lipoproteina levels and monitor safety. Researchers will track changes in lipoproteina concentration at baseline and six months, along with adverse events and treatment tolerability over up to 16 months. The trial aims to understand how pelacarsen affects lipoproteina levels and overall safety when combined with inclisiran in this patient group.

Researchers are evaluating maridebart cafraglutide as an additional treatment to standard care for adults with heart failure who have preserved or mildly reduced ejection fraction, and who are also obese. This phase 3, global, multicenter trial aims to see if this drug can reduce heart failure events like hospitalizations and urgent visits, lower cardiovascular deaths, and improve heart failure symptoms. The study has a double-blind phase and an open-label extension, and it will continue until about 850 primary endpoint events occur. Participants will be randomly assigned to receive either maridebart cafraglutide or a placebo, both given by subcutaneous injection. The trial lasts up to approximately 35 months and includes assessments at various time points to measure heart failure events, cardiovascular deaths, kidney function, blood pressure, weight, blood sugar, cholesterol, and quality of life using questionnaires. The study also tracks serious adverse events and drug concentrations. During the trial, participants will have regular visits for monitoring, including questionnaires, laboratory tests, and physical assessments. Researchers will evaluate the time to first cardiovascular events and heart failure hospitalizations as the main outcome. Secondary measures include changes in symptoms, kidney health, blood pressure, and metabolic factors. Safety will be monitored throughout, with follow-up continuing up to about 35 months from the start of treatment.

Researchers are evaluating treatments for high-risk polycythemia vera PV, a blood condition. This phase III international trial compares the drug ruxolitinib against the best available therapy, which includes hydroxycarbamide or any form of interferon alpha, chosen by the doctor before randomization. The study aims to determine which treatment better prevents serious complications and improves patient outcomes over about three years. Participants will be randomly assigned to one of two groups one receiving oral ruxolitinib 10 mg twice daily, and the other receiving either hydroxycarbamide or interferon alpha via standard hospital care. There is no switching between treatments during the study. The trial is open-label, meaning both doctors and participants know which treatment is given. During the trial, participants will have regular assessments including blood tests, symptom and quality of life questionnaires, and monitoring for events like thrombosis, bleeding, or disease progression. Researchers will track treatment side effects, blood markers, spleen size, and time between blood removal procedures. The study duration is approximately three years per participant, with some outcomes followed up to eight years to assess long-term effects and health economics.

Researchers are evaluating pacing methods to improve symptoms and quality of life for patients with pacemakers. This trial focuses on patients who have a traditional right ventricular RV pacemaker and impaired heart function, testing whether switching to a modern physiological pacing strategy can provide better outcomes. The study is a crossover trial comparing physiological pacing methods to continued RV pacing in patients with pacing-induced cardiomyopathy and heart failure. Participants will first undergo an upgrade procedure to physiological pacing, which may involve His bundle pacing, left bundle pacing, or biventricular pacing if the first two approaches are not possible. After the procedure, there is a one-month recovery period with continued RV pacing. Then participants experience two one-month blinded periods alternating between physiological pacing and RV pacing, followed by two six-month blinded crossover periods. The RV pacing is performed at apical or septal lead locations as per usual practice. During the study, participants will record symptoms monthly using a mobile app or computer. At the end of each period, heart function will be assessed along with a walking test and quality-of-life questionnaires, including the SF-36 survey. Other measurements include left ventricular function, atrial fibrillation monitoring, BNP blood tests, and patient preference surveys. Safety monitoring continues throughout the study, which lasts about fourteen months from baseline to final follow-up.