Bodelwyddan

Researchers are conducting ARISTOCRAT, a phase II, multi-center, double-blind, placebo-controlled, randomized trial to evaluate the cannabinoid Nabiximols compared to placebo in patients with recurrent MGMT methylated glioblastoma treated with temozolomide (TMZ). This trial aims to assess whether adding Nabiximols to standard TMZ therapy improves outcomes in this patient group. The study will enroll a total of 120 patients randomized in a 2:1 ratio to receive either Nabiximols or a matched placebo alongside TMZ. Participants will receive either Nabiximols or placebo as an oromucosal spray combined with oral temozolomide capsules. The trial includes an initial feasibility phase with 40 patients to confirm safety and compliance, followed by full recruitment. Patients undergo MRI scans at screening, week 10, week 22, week 30, and then every 3 months while on treatment. The trial is linked to the Tessa Jowell BRAIN MATRIX program to facilitate patient identification and data sharing. During the study, participants will have 4-weekly follow-up visits for at least 52 weeks or until death. Assessments include MRI imaging, adverse event monitoring, and quality of life evaluations aligned with the linked program. The primary outcome is overall survival time measured from randomization to death from any cause. Safety and treatment compliance will be carefully tracked throughout the trial.

Researchers are evaluating the effect of muvalaplin on reducing cardiovascular risk in adults with elevated lipoprotein(a) levels who either have atherosclerotic cardiovascular disease or are at risk for a heart attack or stroke. This Phase 3, randomized, double-blind, placebo-controlled study focuses on adults with high Lp(a) levels and prior or potential cardiovascular events. The study aims to assess the time to the first major adverse cardiovascular event over about 5.25 years. Participants will be randomly assigned to receive either muvalaplin or a placebo, both administered orally. The study includes individuals with Lp(a) levels of at least 175 nanomoles per liter who have had a prior cardiovascular event within 10 years or are at risk for a first event due to conditions such as coronary artery disease, carotid stenosis, peripheral artery disease, high coronary artery calcium score, reduced kidney function with diabetes, or other high-risk factors. The treatment period lasts through the study duration, with close monitoring. During the study, participants will be regularly evaluated to track the occurrence of major adverse cardiovascular events, including heart attacks and strokes. Safety assessments will monitor blood pressure, kidney function, and heart failure status among other health indicators. The primary outcome measures the time to the first major cardiovascular event from baseline up to the end of the study, which spans approximately 5.25 years.

Researchers are evaluating the effectiveness and safety of bomedemstat compared to hydroxyurea in people diagnosed with essential thrombocythemia (ET) who have not yet received cytoreductive therapy but need it. This Phase 3 study aims to determine if bomedemstat leads to a better lasting clinicohematologic response than hydroxyurea in these patients. Participants will receive either oral bomedemstat capsules or oral hydroxyurea capsules, with placebos used to maintain the study's double-blind design. The study compares these two treatments to see which better manages ET with a focus on sustained treatment response. The treatments are taken as capsules, but specific dosing schedules are not detailed in the available information. During the study, researchers will monitor participants up to 52 weeks to measure their durable clinicohematologic response. Participants will undergo regular assessments to evaluate treatment effects and safety. The study includes safety monitoring and collects data on how well patients respond to the therapies over time, ensuring comprehensive evaluation of both treatments.

Researchers are evaluating treatment options for patients with early-stage classical Hodgkin lymphoma who have not received prior therapy. This international phase III trial runs two parallel studies in different regions, combining data to better understand treatment effects. The trial compares two chemotherapy regimens, ABVD and A2VD, with treatment adapted based on PET-CT scan results after two cycles to guide further therapy. Participants will be randomly assigned to receive either ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine) or A2VD chemotherapy (doxorubicin, brentuximab vedotin, vinblastine, and dacarbazine with growth factor support). PET-CT scans are performed after one cycle for exploratory purposes and after two cycles to determine subsequent treatment. Depending on PET results, patients may receive additional chemotherapy cycles or involved site radiotherapy following ILROG guidelines. Those with poor response discontinue trial treatment and receive alternative therapy. During the study, patients undergo PET-CT scans and regular assessments to monitor treatment response and safety. Follow-up continues for at least five years after treatment completion to assess progression-free survival. Researchers collect clinical data and imaging results to evaluate outcomes, with central review of PET scans guiding treatment adaptations. Participants are monitored for side effects and overall health throughout the trial period.

Researchers are evaluating a phase III randomized clinical trial for patients with unilateral malignant pleural mesothelioma (MPM). The study aims to compare progression-free survival and overall survival between two approaches: proton beam therapy and standard surveillance. Patients will be stratified based on tumor histology, treatment center, tumor side, and time since diagnosis to assess these outcomes. Participants in the experimental group will receive proton beam therapy targeted at the hemithorax, delivering a total dose of 50Gy in 25 daily fractions over five weeks, with an additional boost to 60Gy for visible tumors. The control group will undergo standard care surveillance without immediate treatment, with immunotherapy or chemotherapy offered if disease progression occurs. Both groups will be followed for two years from randomization. During the study, patients will have regular follow-up visits at their local trial sites for assessments including safety, tolerability, quality of life questionnaires, and disease monitoring. The main outcomes measured are progression-free survival and overall survival up to two years. The study plans to recruit 148 patients across 20 UK centers, with additional interim analyses to evaluate treatment efficacy and safety throughout the trial period.

Researchers are studying patients with known or suspected angina who do not have obstructive coronary artery disease to see if a special diagnostic test can help guide personalized treatment. This condition includes ischaemic heart disease, microvascular angina, and vasospastic angina. The trial builds on earlier research suggesting that tailoring treatment based on coronary vascular function tests may improve symptoms and quality of life. This large, multicentre, blinded, randomized study aims to confirm these findings and assess effects on health and wellbeing over a longer period. Participants undergo invasive coronary angiography along with an adjunctive interventional diagnostic procedure (IDP) that measures coronary vascular function using a guidewire technique. Patients with no significant artery blockage are randomized into two groups: one where IDP results are disclosed to guide treatment decisions, and a control group with concealed results receiving standard care. Those with abnormal vascular function in the intervention group may have repeated assessments to tailor medications, such as calcium channel blockers. Patients with obstructive artery disease or other exclusions may join a registry for follow-up and assessment. Throughout the study, participants complete questionnaires about angina symptoms, quality of life, activity levels, treatment satisfaction, and pain. Researchers monitor clinical outcomes for at least 12 months, including major cardiovascular events. The study also evaluates the safety and usefulness of the diagnostic procedure in multiple hospitals across Europe. Blood samples are collected to explore disease mechanisms. Participants and their doctors remain blinded to group assignments, but diagnoses are shared to help guide care following current guidelines.

Researchers are evaluating a medicine called elranatamab for the treatment of multiple myeloma (MM), a type of cancer. This study focuses on people aged 18 or older who have MM that has returned or not responded to previous treatments, including prior use of an anti-CD38 antibody and lenalidomide. The goal is to compare elranatamab to other common combination therapies that include 2 to 3 different MM medicines. This is a Phase 3 study to learn about the safety and effectiveness of elranatamab compared to these other treatments. Participants will be randomly assigned to receive either elranatamab or a combination therapy selected by the study doctor. Elranatamab is given as a shot under the skin at the study clinic about once a week, which may later reduce in frequency. The combination therapy options include medicines taken by mouth and given either as shots under the skin or through a needle in the vein at the clinic. The combination medicines used may be elotuzumab, pomalidomide, dexamethasone, bortezomib, or carfilzomib, depending on the chosen treatment plan. Participants may continue their assigned treatment until their MM stops responding. During the study, participants will visit the clinic regularly for monitoring and evaluation. Researchers will track how well the treatments work by measuring progression-free survival and will watch for any side effects or safety concerns. Follow-up will continue after treatment ends through phone calls or visits. The study may last up to about 5 years to fully assess the outcomes of the treatments.

Researchers are evaluating the safety and effectiveness of palazestrant (OP-1250) compared to standard treatments fulvestrant or an aromatase inhibitor in adults with ER-positive, HER2-negative advanced or metastatic breast cancer. Participants have previously received endocrine therapy combined with a CDK4/6 inhibitor, and their cancer has progressed despite this treatment. This phase 3, international, randomized, open-label trial aims to provide new information on treatment options for this population. Participants will be assigned to receive either palazestrant daily in a 28-day cycle at doses of 90 mg or 120 mg during the dose-selection phase, or standard endocrine therapy with fulvestrant or one of three aromatase inhibitors (anastrozole, letrozole, or exemestane), given according to their approved schedules. After selecting the optimal palazestrant dose, more participants will be randomized to receive either that dose or standard care. Treatment continues until disease progression or unacceptable side effects occur. During the study, participants will be monitored for adverse events, dose reductions, or treatment discontinuation for up to 16 weeks after randomization. The main outcome is progression-free survival, measured until disease progression or death, with an estimated follow-up of up to 2 years. Assessments will include physical exams, lab tests, and regular evaluations of cancer status and side effects to ensure safety and track the effectiveness of the treatments.

Researchers are evaluating a range of treatments to improve outcomes for adults admitted to intensive care units (ICUs) with severe community-acquired pneumonia (CAP), including cases caused by influenza and COVID-19. This Phase 3 adaptive platform trial, REMAP-CAP, is designed to test multiple treatment strategies simultaneously and adapt over time, allowing new treatments to be added as questions are answered. The trial also serves as a platform to quickly evaluate treatments during respiratory pandemics, such as COVID-19, through a sub-study called REMAP-COVID in the United States. Participants receive various interventions including antibiotics like ceftriaxone, moxifloxacin, or piperacillin-tazobactam, as well as macrolide therapies given for different durations. Other treatments assessed include corticosteroids such as hydrocortisone and dexamethasone, antiviral agents like oseltamivir and remdesivir, immune modulators including tocilizumab and baricitinib, and supportive care strategies such as mechanical ventilation methods. Dosing and duration vary for each treatment, with some interventions now closed. Treatments are administered according to local guidelines and clinical decisions, with some requiring intravenous or enteral routes. Participants are closely monitored with assessments focusing on survival and organ support status in the ICU up to 90 days after enrollment. The main outcomes measured include all-cause mortality by day 90 and the number of days alive without needing organ support in the ICU by day 21. The study collects data continuously to adapt treatment assignments for new participants, aiming to identify the most effective therapies. Follow-up and safety monitoring continue throughout hospitalization and up to 90 days after admission.

Researchers are evaluating diagnostic methods at Rapid Diagnostic Centres (RDCs) in England to improve cancer detection in patients presenting with common but unclear symptoms such as weight loss, fatigue, cough, or general practitioner suspicion. These centres aim to provide faster and more personalized cancer diagnosis, especially for patients with non-specific symptoms that are often harder to interpret. The study focuses on developing new blood or non-blood tests to identify which patients have cancer and which are at higher risk for future cancer, enhancing current diagnostic pathways. The study will collect breath, blood, and saliva samples from approximately 1000 patients attending RDCs. Breath samples will be collected from around 300 patients, while blood and saliva samples will be collected from about 1000 patients. Samples will be taken at the first appointment and potentially at up to three follow-up visits if needed. The study will use these samples alongside routine clinical data, imaging scans for some patients, and patient questionnaires to develop tests that can distinguish cancer from non-cancer cases and identify cancer types. Each participant will be assigned a unique Study ID to protect their personal information. Participants will provide clinical data, biological samples, and health questionnaires at multiple appointments. Researchers will analyze the accuracy of clinical data review, polygenic risk scores, imaging radiomics, and multiparametric machine learning analyses over a 5-year period. Patients will be followed for 12 months after recruitment to confirm diagnoses or monitor stability. The study aims to develop tests that can correctly classify patients and support earlier cancer detection while protecting patient privacy and maintaining confidentiality throughout the study.