Winchester

Researchers are evaluating the use of epigenome-guided treatment selection compared to the usual standard-of-care (SOC) treatment in adults with active Crohn's Disease (CD) who are starting biologic therapy. This multicenter, prospective, randomized, controlled, open-label study aims to assess the efficacy, safety, and cost-effectiveness of this approach by comparing clinical remission and endoscopic response at Week 26. About 378 participants with active CD, defined by specific clinical and endoscopic criteria, will be included, with roughly half being biologic-naive and the other half exposed to no more than one prior biologic treatment. Participants will be randomly assigned to either receive biologic therapy guided by an epigenetic biomarker assay and the EpiPredict software, which predicts response to two biologics (Vedolizumab or Ustekinumab) or to receive treatment selected according to usual SOC without epigenome guidance. Biologic therapies will be administered following product labels and local SOC recommendations, with dose adjustments allowed as needed. Study assessments will follow the SOC schedule for each biologic during the 26-week treatment period, with different visit weeks depending on the biologic used. Participants will undergo blood sample collection for epigenetic testing during screening. Study visits will include clinical and endoscopic assessments at specified weeks, with long-term follow-up every six months up to 24 months after Week 26 using medical records and questionnaires. Researchers will measure outcomes related to clinical remission and endoscopic response, safety, and cost-effectiveness. Participants' adherence and ability to comply with protocol requirements will be monitored throughout the study.

This research aims to understand the genetic factors that contribute to the risk of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). GCA is a serious inflammatory disease affecting blood vessels, mainly in people over 50, which can cause severe complications like vision loss or stroke if untreated. PMR causes pain and stiffness in the limbs with signs of inflammation. The study involves both patients recently suspected of having GCA and those with confirmed diagnoses from the past. It seeks to provide new insights into disease causes and improve diagnosis and treatment approaches. Participants are observed in a multi-center study collecting clinical and genetic data. The study includes both prospective patients with suspected GCA and retrospective patients with confirmed GCA or PMR diagnoses. Some retrospective participants receiving tocilizumab for recurring or difficult-to-treat GCA are also included in a safety monitoring registry. Data collected include clinical features, imaging, tissue and blood samples, and advanced genetic testing. The study also follows patients over time to assess disease impact, quality of life, and long-term outcomes. During the study, participants provide medical information, biological samples, and complete questionnaires about their symptoms and quality of life. Researchers monitor disease activity and treatment effects, especially among those starting certain immune-modifying drugs. The main measurements focus on genetic susceptibility at the study start, with ongoing evaluation of diagnosis, prognosis, and disease progression. The study is designed to improve understanding and management of GCA and PMR over time.

Researchers are investigating the safety and effectiveness of adding olaparib, a PARP enzyme inhibitor, to platinum-based chemotherapy given before surgery in patients with triple-negative breast cancer (TNBC) and/or those with germline BRCA (gBRCA) mutations. This randomized phase II/III trial aims to see if this combined treatment improves the rate of pathological complete response (pCR) at surgery while monitoring safety outcomes. The study plans to enroll at least 780 patients, including a minimum of 220 with gBRCA mutations. Participants will receive a minimum of 21 weeks of chemotherapy followed by surgery. The treatment includes oral olaparib tablets taken twice daily about 12 hours apart, alongside intravenous paclitaxel and carboplatin given in cycles every three weeks. During the trial, standard supportive care like granulocyte-colony stimulating factor and anthracyclines may also be administered. For those with residual disease after initial treatment, there is an option to join a sub-study involving additional chemotherapy drugs. Throughout the study, patients will undergo screenings including BRCA mutation testing and various tumor marker assessments. Safety will be closely monitored by the trial team and an independent committee. The main outcomes measured are treatment-related side effects, pCR rates after surgery, and long-term efficacy assessed over approximately 5.5 years, with follow-up planned for up to 10 years after surgery.

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 studying advanced pelvic cancers, which are complex and require treatments like radiotherapy, chemotherapy, and extensive surgery involving multiple pelvic organs. These surgeries often result in complications related to the empty pelvis syndrome and perineal wound closure, affecting recovery and quality of life. The study aims to evaluate how different reconstruction methods after surgery influence complication rates, patient quality of life, and healthcare costs, to improve decision-making for patients and doctors. The study has three parts: first, maintaining a database of patients undergoing colorectal surgeries including pelvic exenteration and abdominoperineal excision, collecting detailed clinical data, imaging, complications, and patient outcomes. Second, a national prospective study where patients undergoing these surgeries complete quality of life and financial impact questionnaires before surgery and at 3, 6, and 12 months after surgery. The surgical reconstruction method is chosen by the surgeon. Third, a qualitative study involving interviews with patients at 3 and 12 months post-surgery to explore experiences and quality of life in depth. Participants provide clinical information and complete various patient-reported outcome measures including quality of life and financial toxicity questionnaires. Researchers monitor surgical details, complications, healthcare use, and survival. Follow-ups involve telephone or email contacts for questionnaire completion. Data analysis includes statistical modeling and health economic evaluation. The qualitative interviews are recorded, transcribed, and analyzed to identify themes over time. The study lasts up to 12 months of follow-up after surgery, with patient involvement throughout.

Stroke is a major health issue worldwide and a leading cause of disability. Managing blood pressure is crucial for stroke patients, and measuring central blood pressure and arterial stiffness provides important information beyond the usual arm blood pressure readings. This study is looking at whether a device called the Vicorder, which is less operator dependent and quicker to use, is reliable and accurate for measuring pulse wave velocity and transit time in people who have had a stroke, compared to established devices like the SphygmoCor XCEL and Doppler Ultrasound. In this study, twenty stroke patients will attend four separate 2-hour assessment sessions with at least 24 hours between each. Before each session, participants will fast overnight and can take their usual medications on assessment days. During the first two sessions, participants will be randomly assigned to either a lying down (supine) or seated position and have multiple blood pressure and pulse wave velocity measurements taken using both the Vicorder and SphygmoCor XCEL devices. Ultrasound scans and ECG recordings will also be performed to measure arterial stiffness and blood flow in several arteries on both sides of the body. Sessions three and four will involve further measurements with the Vicorder while participants rest in supine and seated positions. Participants will be closely monitored with blood pressure, pulse wave analysis, ECG, and ultrasound scans throughout the study. Researchers will collect triplicate measurements of pulse wave velocity and transit time in different artery segments to compare device accuracy and consistency. The total involvement includes four visits, each lasting about two hours, where various assessments and scans will be performed to evaluate the Vicorder device against established methods for stroke patients.

Waldenstrf6m's macroglobulinaemia (WM) is a rare, slow-growing lymphoma where abnormal white blood cells develop, mostly affecting older adults with a median age over 70. Current treatments often lead to incomplete responses and disease recurrence, so this study seeks better first-line therapies to improve outcomes and quality of life. The RAINBOW trial is a combined phase 2 and 3 study comparing a chemotherapy-free regimen to standard chemotherapy in patients newly diagnosed with WM. The study compares two treatment plans: one group receives rituximab and ibrutinib (RI) without chemotherapy, while the other group receives the standard combination of dexamethasone, rituximab, and cyclophosphamide (DRC). Eligible adults with untreated WM will be randomly assigned to either group and receive up to 6 treatment cycles. Those on the RI arm may continue ibrutinib alone for up to 5 years after initial therapy. Treatment response is assessed after 3 cycles and at 24 weeks. Participants will be closely monitored throughout treatment and then every 3 months for 5 years after stopping therapy. Annual follow-up for survival continues until the trial ends, which is expected to last about 9 and a half years. Researchers measure treatment effectiveness by overall response rates at 24 weeks and progression-free survival up to 2 years after the last patient is randomized, with ongoing safety and quality of life assessments.

Stroke occurs when blood flow to the brain is interrupted, often leading to difficulties with walking. Regaining walking ability is important for stroke survivors to improve independence and overall health. This research evaluates a rehabilitation method called robot-assisted gait training (RAGT) using a device named the Lokomat, which helps patients take steps with the aid of a treadmill, harness, and robotic suit. The study focuses on whether this training improves cardiovascular health and physical activity levels in early-subacute stroke patients. The study compares stroke patients at two NHS inpatient units: one where patients receive RAGT with the Lokomat as part of standard care, and another where patients do not receive RAGT. Data will be collected retrospectively and matched based on walking ability, blood pressure, and age. Participants using the Lokomat will receive training as determined by their care team, with no changes due to study participation. The non-RAGT group will receive usual care without the robotic device. Participants will undergo assessments at baseline, every two weeks during inpatient care up to six weeks, and a follow-up at three months post-stroke. Tests include pulse wave velocity and pulse wave analysis to measure cardiovascular health, wearing an accelerometer for physical activity monitoring, and functional walking tests like the Timed Up and Go, Functional Ambulation Category, and 2-minute walk test. These evaluations are safe, non-invasive, and mostly conducted at the hospital or at home if discharged. The study will analyze and compare results between groups, with participants receiving personal and overall study reports after completion.

The trial investigates the role of ixazomib in patients with relapsed multiple myeloma who have previously undergone autologous stem cell transplant (ASCT). This phase III, open-label, randomized, controlled study aims to evaluate whether adding a proteasome inhibitor to the salvage ASCT conditioning improves the depth of response, and to assess the impact of consolidation and maintenance treatments on the durability of response. The study also looks at overall survival, progression time, quality of life, and treatment safety among participants with measurable disease and good performance status. All participants first receive re-induction therapy consisting of 4 to 6 cycles of ixazomib, thalidomide, and dexamethasone (ITD) over 28-day cycles to achieve maximum disease control. Those who reach stable disease or better are randomized to receive either conventional ASCT using melphalan or augmented ASCT combining melphalan with ixazomib. Following this, participants who maintain minimal response or better undergo a second randomization to either receive consolidation therapy with 2 cycles of ITD followed by ixazomib maintenance until disease progression, or no further treatment. During the study, participants will undergo regular assessments including blood tests, disease response evaluations, and monitoring for adverse effects. The primary outcomes measured are overall response rate 100 days after ASCT and progression-free survival up to 10 years. Secondary evaluations include overall survival, time to disease progression, minimal residual disease status at various stages, engraftment kinetics, and quality of life. Follow-up continues with clinic visits every three months until disease progression is observed, enabling long-term monitoring of treatment effects and safety.

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.