Worthing

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 evaluating whether reducing the frequency of pembrolizumab treatment after six months of standard therapy is safe and effective for patients with advanced non-small cell lung cancer (NSCLC). Pembrolizumab, an immunotherapy targeting the PD-1 receptor on T cells, has improved outcomes for this condition. Because pembrolizumab remains bound to its target for a long time and dosing frequency may not affect outcomes, this study aims to find out if less frequent dosing can maintain effectiveness while reducing overtreatment and side effects. This phase III study also considers potential benefits like cost savings and improved quality of life due to fewer hospital visits. Participants who have completed six months of pembrolizumab treatment without disease progression and are continuing therapy will be randomly assigned to receive pembrolizumab at the standard six-week interval or at a reduced frequency of 12 weeks. If early results show that the 12-week schedule is not less effective, later participants may be randomized to even longer intervals of 9, 15, or 18 weeks. Pembrolizumab is given intravenously at 400 mg per dose. Patients whose disease progresses on a reduced frequency schedule may return to the standard six-week treatment. During the study, researchers will monitor overall survival at two years after randomization. Participants will undergo regular assessments to track disease status, treatment tolerability, and overall health. The study aims to confirm that less frequent dosing does not reduce survival while potentially improving patient experience. The trial is open to adults aged 18 and older with advanced NSCLC who have already completed six months of pembrolizumab therapy and intend to continue treatment.

Researchers are evaluating the combination of bleximenib, venetoclax (VEN), and azacitidine (AZA) compared to placebo with venetoclax and azacitidine alone in treating adults newly diagnosed with acute myeloid leukemia (AML) who have specific gene mutations (NPM1 or KMT2A) and are not eligible for intensive chemotherapy. This is a phase 3 randomized, double-blind, placebo-controlled study focusing on participants with AML harboring these genetic abnormalities. The study aims to assess treatment effectiveness by measuring complete remission rates and overall survival. Bleximenib and venetoclax are given orally, while azacitidine is administered either intravenously or under the skin. Participants will receive either the combination of bleximenib, venetoclax, and azacitidine or placebo with venetoclax and azacitidine, following a rigorous treatment schedule. The study includes an initial treatment period where the effects of these drugs are compared to determine their impact on AML with the given mutations. Participants will be closely monitored through regular assessments, including evaluations of remission status and survival over a period of up to 4 years and 1 month. Safety and treatment responses will be tracked throughout the study. Participants must consent to follow the study procedures and agree to contraception requirements during and after treatment. The trial involves continuous observation to gather comprehensive data on treatment outcomes and participant health.

A total hip replacement is a common and effective orthopedic surgery that replaces both the ball and socket of the hip to relieve pain and help patients return to normal activities. This research evaluates the JRI Orthopaedics ACE Acetabular Cup System, which features a special coating to help the implant bond with the bone. The study is designed to monitor the safety and performance of this CE-marked device over a 10-year period by assessing clinical, functional, and radiological outcomes in patients who have received this implant. Participants will receive a primary elective total hip replacement using the ACE Acetabular Cup System. This device offers three types of socket liners—ceramic, polymer, or dual mobility—to provide surgical options tailored to the patient's needs. The study is conducted at multiple UK centers and follows patients long-term to gather data on the device's performance and safety. Throughout the study, patients will complete questionnaires, undergo X-rays, and report any complications related to their hip replacement. The main outcome measured is the Oxford Hip Score three years after surgery, which evaluates hip function and pain. The study includes ongoing monitoring for up to 10 years to ensure comprehensive assessment of the implant's durability and patient outcomes.

Researchers are evaluating the effectiveness and safety of adding oral anticoagulation (OAC) to standard antiplatelet therapy in patients who develop new-onset post-operative atrial fibrillation (POAF) after isolated coronary artery bypass graft (CABG) surgery. This phase 3, multicenter, open-label, randomized trial aims to compare the prevention of thromboembolic events like stroke or heart attack against the risk of major bleeding. Patients who decline randomization may join a parallel registry to capture their treatment choices and risk profiles. Participants will be randomly assigned to one of two groups: the OAC-based strategy group receiving oral anticoagulants such as vitamin K antagonists or direct oral anticoagulants combined with antiplatelet therapy, or the control group receiving antiplatelet therapy alone with aspirin or a P2Y12-inhibitor. The anticoagulation treatment is given for 90 days, with the possibility for patients in the control arm who develop recurrent atrial fibrillation after 30 days to switch to anticoagulation. The study follow-up includes visits at 90 days and phone calls at 30, 60, and 180 days. Up to 500 patients may participate in a digital health substudy using a wearable heart rhythm monitor for 30 days after discharge. During the study, researchers will monitor participants for serious events such as death, ischemic stroke, transient ischemic attack, myocardial infarction, and thromboembolism up to 180 days after randomization. Safety is assessed by tracking major bleeding events up to 90 days. Data from the registry group will be analyzed to compare risk profiles and treatment strategies. Participants will be evaluated through clinical visits, phone follow-ups, medical record reviews, and in some cases, digital monitoring to understand treatment effects and safety over time.

Researchers are evaluating the safety and effectiveness of whole-body hypothermia treatment in newborn babies diagnosed with mild hypoxic ischaemic encephalopathy (HIE). This phase III randomized controlled trial aims to determine whether cooling babies to 33.57b0C within six hours of birth for 72 hours improves cognitive development at two years of age compared to maintaining normal body temperature (normothermia). The study also assesses the cost-effectiveness of cooling therapy to help guide national and international treatment guidelines and standardize care across the NHS. Babies born at or after 36 weeks with specific signs of birth asphyxia or acidosis are randomly assigned to either whole-body hypothermia or targeted normothermia groups. The hypothermia group will have their body temperature lowered and maintained at 33.57b0C using a cooling machine for 72 hours in a neonatal intensive care unit. The normothermia group will have their temperature maintained at 377b0C with treatment for any fever using standard protocols. If babies in the normothermia group develop seizures and worsen to moderate HIE, they may receive cooling treatment as part of clinical care. Conventional MRI scans will be performed before discharge. Participants will be followed up at 24 months of age (7 months) using the Bayley Scales of Infant and Toddler Development IV to measure cognitive, language, and motor skills. Additional neurological exams, including assessments for cerebral palsy, vision, and hearing, will be conducted. Parents will complete questionnaires about their child's development. Researchers will collect detailed clinical data from birth through follow-up to evaluate safety and developmental outcomes. Babies who die or cannot complete assessments due to severe disability will be assigned specific scores to reflect outcomes.

Atrial fibrillation (AF) is a common heart rhythm problem that can cause strokes due to blood clots. Even with treatment using direct oral anticoagulants (DOACs), patients with AF still face a risk of stroke. This trial focuses on patients with AF who have recently had an ischemic stroke despite being on anticoagulant therapy. Researchers want to find out if adding a procedure called left atrial appendage occlusion (LAAO) to DOAC therapy can better prevent future strokes compared to using DOAC therapy alone. Participants in the study will be randomly assigned to one of two groups. One group will receive the combination of LAAO plus DOAC therapy, while the other group will continue on DOAC therapy alone. The choice of which DOAC to use is left to the treating doctor. The study will follow patients for a minimum of 6 months, with regular check-ins every 6 months, and may continue for up to 48 months. The design includes careful monitoring to compare the effects of the two treatments on preventing further strokes and other heart-related events. During the trial, researchers will monitor participants for the first occurrence of stroke, systemic embolism, or cardiovascular death as the main outcome. They will also assess safety by tracking bleeding events and complications related to the device or procedure. Functional outcomes and patient experiences will be recorded as well. The study requires patients to have ongoing anticoagulant therapy at stroke onset and regular follow-ups for up to four years to gather comprehensive data on treatment effectiveness and safety.

Researchers are evaluating the effectiveness, safety, and tolerability of subcutaneous lunsekimig compared to a placebo in adults aged 40 to 80 years with inadequately controlled chronic obstructive pulmonary disease (COPD) characterized by an eosinophilic phenotype. This Phase 2b/Phase 3, parallel, 3-arm study focuses on participants who have a history of COPD with an eosinophilic profile and have not achieved control with current treatments. Eligible participants will receive either lunsekimig or a matching placebo through subcutaneous injections over a randomized treatment period of approximately 48 weeks. The study involves three periods: an initial screening period lasting up to 4 weeks, followed by the 48-week treatment period, and finally an 8-week follow-up period. The total study duration may last up to 60 weeks. During the study, participants will be regularly assessed for the annualized rate of moderate-to-severe COPD exacerbations from baseline up to 48 weeks. Researchers will monitor safety, tolerability, and treatment effects through various evaluations throughout the treatment and follow-up periods. Participant involvement includes completing assessments and receiving scheduled injections as part of the study protocol.

Researchers are evaluating the optimal duration of antibiotic treatment for adults with complicated intra-abdominal infections (cIAI). This Phase 3 trial aims to compare a fixed extended duration of 28 days of antibiotics to the current standard care durations, which typically range from 7 to 18 days. The study will assess clinical outcomes, quality of life, and cost effectiveness over a 180-day follow-up period to determine which approach may better reduce treatment failure and improve patient care while considering antimicrobial resistance concerns. Participants will be randomly assigned to one of two groups: the standard care group, where antibiotic type and duration are determined by their clinician, or the fixed extended-duration group, which receives antibiotics for a set 28-day period. The study includes a total of 1166 adult patients recruited from intensive care units and hospital wards across approximately 30 NHS trust hospitals. The treatment period is followed by monitoring up to 180 days after randomization. During the study, patients or their personal consultees will complete quality of life questionnaires at baseline and at 30, 60, and 180 days post-randomization. They will also provide information about antibiotic use and healthcare resource utilization. Researchers will collect hospital records on admissions, relapses, and further infections. The main outcome measured is treatment failure within 180 days of randomization, with safety and effectiveness assessed throughout the follow-up period.

Researchers are investigating whether adding palliative rehabilitation to usual care can improve the quality of life for patients with incurable solid cancers such as lung, colorectal, breast, and prostate cancer. The study focuses on adults aged 18 and over who have advanced cancer that cannot be cured, aiming to see if this combined approach helps patients live better despite their illness. The trial is taking place across multiple European countries and involves 340 participants recruited from hospitals. Participants are randomly assigned to either receive usual care alone or usual care plus the INSPIRE rehabilitation intervention. Those in the rehabilitation group can have up to three sessions delivered by expert therapists, either face to face or remotely by phone or video. These sessions focus on symptom management, physical activity, fitness, and social participation, using goal setting and action plans. The rehabilitation visits occur within seven weeks after joining the study. Both groups complete questionnaires at 4, 8, and 16 weeks to measure their progress. During the 16-week participation, data such as medical history and demographics will be collected and kept confidential. The study measures health-related quality of life at 8 weeks after enrollment, with additional follow-up through medical record reviews at 28 weeks. Participants allocated to rehabilitation may also be invited for an optional interview about their experience. The study aims to provide insights into how rehabilitation fits into current cancer care and its potential benefits for patients with advanced cancer.