Carmarthen

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 investigating colorectal cancer (CRC) patients with newly diagnosed stage I, II, and III cancers to evaluate whether mutations in circulating tumor DNA (ctDNA) can predict disease relapse earlier than current methods. This study includes two parts: Part B focuses on analyzing tumor tissue, serial blood samples, and clinical data to detect minimal residual disease (MRD) and predict relapse, while Part C is a randomized study comparing ctDNA-guided adjuvant chemotherapy to standard care in high-risk stage II or III CRC patients post-surgery. In Part B, the study collects serial blood samples from patients who have undergone potentially curative surgery to detect and quantify ctDNA, aiming to identify MRD and predict relapse. Part C randomizes patients after surgery into two groups: one receiving standard adjuvant chemotherapy and the other receiving ctDNA-guided chemotherapy, where those testing ctDNA negative may have chemotherapy reduced. The goal is to assess if ctDNA-guided treatment can safely reduce chemotherapy use without compromising disease-free survival. Participants will undergo tumor tissue collection, blood sampling at multiple time points, and clinical assessments over several years. Researchers will monitor ctDNA levels and clinical outcomes, measuring disease-free survival up to 3 to 6 years. Safety and treatment effects will be evaluated, with follow-up visits to track relapse and treatment response. Total participation includes long-term monitoring for relapse prediction and chemotherapy guidance.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease that causes scarring, leading to coughing and breathlessness. Many people with IPF also have reflux disease, where stomach acid may enter the lungs and cause damage. This research is evaluating whether using proton pump inhibitors (PPIs), medicines that reduce stomach acid like lansoprazole, can slow the progression of IPF. The study is a phase 3 clinical trial involving 298 IPF patients from about 37 UK hospitals to determine if treating with PPIs affects IPF outcomes and cough, reflux, and sleep symptoms. Participants will be randomly assigned to take either lansoprazole 30 mg capsules or matching placebo capsules twice daily, about 12 hours apart, for 12 months. They will be asked to start weekly home breathing tests using equipment provided, and some with a cough will use a device to count coughs over 24 hours. Questionnaires on cough, breathlessness, sleep, and general health will be completed. A sub-study involves additional cough and sleep monitoring sessions. Participants may reduce the dose if side effects occur. Throughout the study, participants will complete home spirometry assessments weekly, provide blood samples for safety checks at set intervals, and answer questionnaires at 3, 6, 9, and 12 months. Visits may be remote or in person. Researchers will monitor medication adherence, medical history changes, and side effects. The main outcome measured is the change in lung function, specifically forced vital capacity, 12 months after randomization. Additional blood samples may be collected for future research with consent.