Portsmouth

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.

The aim is to assess how closely international asthma guidelines agree in diagnosing asthma and to explore additional evidence of airways disease using physiologic criteria such as impulse oscillometry IOS, which is not included in current guidelines but is available through the Portsmouth lung function service. Asthma diagnosis is based on indicators such as airflow obstruction, airway sensitivity, and inflammation, but guidelines from NICE, GINA, and BTSSIGN use different diagnostic criteria, which can lead to inconsistencies in identifying patients with asthma. IOS is a simple, non-invasive lung function test that may improve the accuracy and ease of asthma diagnosis, although evidence for its use in adults remains limited. Routine outpatient lung function data from patients attending the severe asthma service at Queen Alexandra Hospital in Portsmouth will be analysed using an opt-out consent process. The analysis will focus on the usefulness of IOS compared with other lung function indices in diagnosing asthma. The findings may help refine asthma diagnostic methods and potentially expand the diagnostic toolkit to include IOS, improving the precision and ease of asthma diagnosis and management.

Researchers are evaluating the long-term safety and tolerability of dazodalibep in people with Sjgrens Syndrome. This phase 3 open-label study extends previous trials by continuing to monitor participants who completed 48 weeks of treatment with dazodalibep or placebo. The study is sponsored by Amgen and aims to better understand the safety profile of dazodalibep over an extended period. Participants who finished the initial 48-week trials HZNP-DAZ-301 or HZNP-DAZ-303 will receive an assigned dose of dazodalibep intravenously for an additional 132 weeks. This extension study involves a single treatment group receiving dazodalibep without placebo, focusing on ongoing treatment effects and participant safety. During the study, participants will be monitored for treatment-emergent adverse events for up to 152 weeks. Researchers will also measure the presence of anti-drug antibodies and plasma concentrations of dazodalibep for up to 132 weeks. Participants need to be available for all study visits and procedures, with safety assessments conducted regularly throughout the long-term extension period.

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 evaluating two new treatments compared to the best standard care for men with prostate cancer that has spread to other parts of the body and still responds to hormone therapy. This phase 3 trial includes multiple hospitals across the UK and is led by University College London. The study aims to see if adding targeted radiotherapy or a radioactive drug can slow cancer spread and improve survival. Participants are assigned by computer to one of several groups. One group receives standard care, which includes androgen deprivation therapy ADT plus other hormone therapies, possible chemotherapy with docetaxel, and local radiotherapy. Another group receives standard care plus targeted high-dose radiotherapy SABR to metastatic sites. A third group receives standard care plus a radioactive therapy called 177Lu-PSMA-617, given in cycles with two doses per cycle. Treatments continue unless side effects are severe or participants choose to stop. During the study, participants will have scans and tests to monitor their cancer and side effects. Doctors will check safety and treatment adherence over time. Researchers will measure overall survival, failure-free survival, progression-free survival, prostate cancer-specific survival, and quality of life up to 10 years from randomization. Safety will be closely monitored, and participants health will be followed during and after treatment.

Researchers are evaluating how well JNJ-79635322 works compared with an anti-B-cell maturation antigen BCMAxCD3 bispecific antibody in adults with relapsed or refractory multiple myeloma. This phase 3 study includes participants who have received at least three prior therapies and have progressive disease or insufficient response to their last treatment. The study aims to assess treatment outcomes including overall response and progression-free survival over a period of up to 5 years and 7 months. Participants are randomly assigned to receive either JNJ-79635322 or teclistamab, both given as subcutaneous injections. Treatment continues until disease progression or intolerable side effects occur. These two groups allow comparison of the effects of each drug on disease control and patient well-being during the study. During the study, participants undergo regular assessments to monitor their response to treatment, including laboratory tests to measure disease markers and evaluations of symptoms, functioning, and quality of life. Researchers will track adverse events, immune responses to the drugs, and long-term outcomes such as duration of response and overall survival. The total participation time can extend up to nearly 6 years, with ongoing monitoring of symptoms and quality of life throughout this period.

Researchers are evaluating the efficacy and safety of two different dose regimens of pegozafermin compared to a placebo in adults with metabolic dysfunction-associated steatohepatitis MASH who have liver fibrosis stage F2 or F3. This Phase 3 study aims to better understand how pegozafermin may impact liver fibrosis and steatohepatitis in this population. Participants will receive subcutaneous injections of either one of two pegozafermin regimens or a matched placebo. These treatments are given in parallel groups, and participants are randomly assigned to one of the study groups. The study compares the effects of pegozafermin on liver fibrosis and steatohepatitis over a treatment period that includes evaluations up to 52 weeks and monitoring for disease progression up to 5 years. During the study, participants will be monitored through biopsies and blood tests to assess liver fibrosis improvement, resolution of steatohepatitis, changes in liver enzyme levels, and enhanced liver fibrosis scores. Safety and disease progression are also tracked throughout the study period. The total participation duration includes treatment and long-term observation to evaluate outcomes and any potential changes in liver health.

Lung cancer is the leading cause of cancer deaths in the UK, often diagnosed late. Current screening mainly targets high-risk groups, missing about 30% of cases, including many women and never-smokers. There is a need for a simple, non-invasive test to help triage patients with persistent respiratory symptoms who do not meet current screening criteria. The Inflammacheck4 device measures hydrogen peroxide and other breath markers linked to airway inflammation and oxidative stress. Previous studies showed it could distinguish lung cancer from other respiratory diseases well. This study aims to validate and improve the AI model behind Inflammacheck4 for quick and accurate lung cancer triage in NHS settings. This is a multi-center, observational study without intervention or randomization. Participants include healthy volunteers and people with lung cancer, suspected lung cancer negative biopsy, pneumonia, non-malignant airway diseases, or other respiratory conditions. The study collects exhaled breath samples using Inflammacheck4 alongside demographic and clinical data. The AI model will be refined by analyzing these breath biomarkers across the different groups. The study includes both retrospective and prospective data integration. Participants will provide breath samples and allow access to clinical data and imaging results. The primary outcome is to refine the AI-based diagnostic model from enrollment until study completion in December 2026. Participants must be able to understand English and perform the breath test. The study excludes those with active infections other than pneumonia, recent major lung surgery, recent cancer treatments, pregnancy, or recent smoking or certain medication use. The total participation time depends on individual enrollment and data collection timing.

Researchers are evaluating the anti-tumor activity and safety of amivantamab administered as a subcutaneous co-formulation with recombinant human hyaluronidase PH20 rHuPH20 in participants with advanced or metastatic solid tumors, including non-small cell lung cancer NSCLC with specific EGFR mutations. This study focuses on various cohorts, some receiving combination treatments, and others monitoring safety of the co-formulation alone. Participants receive amivantamab subcutaneously at doses adjusted by body weight, combined with treatments such as lazertinib orally, pemetrexed and carboplatin intravenously, or anticoagulants as appropriate. Dosing schedules vary by cohort, typically involving initial frequent doses followed by maintenance cycles every 21 or 28 days. Some participants may enter a long-term extension phase to continue receiving study treatments. During the study, participants undergo evaluations including tumor response assessments using RECIST 1.1 criteria, safety monitoring through adverse event tracking, laboratory tests, and patient-reported outcomes. Follow-up assessments occur up to several years depending on cohort. Participants eligibility includes confirmed NSCLC with specific EGFR mutations and adequate organ function, with monitoring of treatment safety and efficacy throughout their participation.

Researchers are evaluating Risvutatug Rezetecan Ris-Rez, a new medicine targeting specific proteins on cancer cells, in adults with relapsed extensive-stage small cell lung cancer ES-SCLC. This phase 3 study aims to compare how well Ris-Rez works versus the standard treatment, topotecan, by measuring cancer shrinkage, disappearance, and overall survival. The study also monitors safety, side effects, and tolerability of both treatments. Participants will be randomly assigned to receive either Ris-Rez or topotecan. Both treatments will be administered as part of the study to assess their effects. The study will follow participants for up to approximately 139 weeks to evaluate multiple outcomes including survival, tumor response, disease progression, and brain metastasis control. During the study, participants will have regular evaluations including scans, laboratory tests, vital signs, electrocardiograms, and performance status assessments. Researchers will track adverse events, laboratory changes, and participant experiences with the study drugs. The main outcome measured is overall survival up to about 113 weeks, with additional long-term monitoring of other health and disease measures throughout the study.