Dorchester

This research aims to demonstrate the acceptable performance and assess the safety of the HARMONIC 700 Shears device when used as instructed in both pediatric and adult surgical procedures. The study focuses on its use in general pediatric surgeries as well as general, gynecological, urological, and thoracic surgeries in adults. It evaluates the device in a post-market setting to ensure its reliability across these types of surgeries. The study involves using the HARMONIC 700 Shears for vessel transection according to the device's instructions for use. There is no additional intervention beyond the necessary clinical care during the procedures. The device is applied in surgeries where at least one vessel is planned to be transected, covering a range of general and specialized surgical procedures for both children and adults. Participants will be monitored during surgery to measure the number of vessel transections achieving effective hemostasis and to track any device-related adverse events up to approximately 1 year and 7 months after the procedure. The study assesses both the intraoperative performance of the device and its longer-term safety, involving follow-up assessments to evaluate outcomes and any potential complications.

This research aims to evaluate the safety of maribavir in adults who have severe chronic kidney disease (CKD) or end-stage renal disease (ESRD), including those undergoing dialysis, and who have a cytomegalovirus (CMV) infection after receiving a transplant. The study focuses on patients who have had either a solid organ transplant or a hematopoietic stem cell transplant and later developed refractory CMV infection during the post-transplant period. The study is non-interventional and involves collecting existing data from participants' medical records without affecting their regular medical care or treatment. Participants included are those who started maribavir treatment as part of routine practice and received at least one dose. The study reviews data collected during normal clinical routines to assess safety outcomes related to maribavir use in this specific patient population. Participants' medical records will be reviewed to track adverse events from the start of maribavir treatment until seven days after the last dose or death, with follow-up lasting up to four years. No additional treatments or interventions are given as part of the study, and it only involves reviewing past clinical information. The data collected will help determine the safety profile of maribavir in these patients with kidney failure and CMV infection.

This research aims to evaluate the safety and effectiveness of pumitamig combined with chemotherapy compared to bevacizumab combined with chemotherapy in adults with previously untreated, unresectable, or metastatic colorectal cancer. The study is a blinded, randomized Phase 2/3 trial targeting participants with histologically confirmed recurrent or metastatic colorectal adenocarcinoma that cannot be cured with surgery. Participants must not have certain genetic markers such as mismatch repair deficiency, microsatellite instability-high status, or BRAF V600E mutation. Participants will receive either pumitamig or bevacizumab along with chemotherapy regimens including FOLFOX, FOLFIRI, or CAPOX at specified doses and schedules. The interventions involve administering these drugs on specified days, though exact dosing details are not provided. The study compares these two treatment combinations to assess their safety and efficacy in this patient population. Throughout the study, participants will be monitored for tumor response using RECIST v1.1 criteria, progression-free survival, and overall survival for up to five years. Researchers will evaluate confirmed complete or partial tumor responses, survival rates, and disease progression. The study includes regular assessments to track treatment effects and safety over a long-term follow-up period, ensuring comprehensive monitoring of participant outcomes.

Researchers are conducting a two-part, phase 2b/3 study to evaluate CSL300 (Clazakizumab) in adults with end stage kidney disease (ESKD) undergoing dialysis who have systemic inflammation and either atherosclerotic cardiovascular disease (ASCVD) or diabetes. The study aims to determine the best dose of CSL300 and assess its effects on cardiovascular outcomes and safety in this population. This multicenter, randomized, double-blind, placebo-controlled trial targets patients with elevated inflammation markers and significant health risks due to their conditions. In the first part (phase 2b), the study focuses on finding the appropriate dose of CSL300 compared to placebo. CSL300 is given through intravenous (IV) administration. The second part (phase 3) evaluates the impact of CSL300 on cardiovascular events such as heart attack or cardiovascular death over approximately 5 years, continuing to compare CSL300 to placebo for safety and efficacy. The placebo matches CSL300's excipient content but lacks the active drug. Participants will undergo baseline and regular assessments for inflammation markers like high-sensitivity C-reactive protein (hs-CRP) up to 12 weeks in phase 2b, and long-term monitoring for cardiovascular outcomes in phase 3. The study involves ongoing safety evaluations and efficacy measurements during the entire follow-up period. This comprehensive approach helps researchers understand how CSL300 affects inflammation and cardiovascular health in patients with ESKD on dialysis.

Researchers are investigating the effects of a medicine called BI 690517 in combination with empagliflozin for adults with chronic kidney disease who are at risk of their condition worsening. This study includes people both with and without type 2 diabetes and those already taking certain kidney-related medicines like ACE inhibitors or angiotensin receptor blockers. The goal is to understand if adding BI 690517 helps protect kidney function and reduces risks related to kidney failure and heart problems. This is a Phase 3 clinical trial conducted over about 3 to 4 years. The study has two parts. First, participants receive either empagliflozin or a placebo similar to BI 690517 for at least six weeks, while continuing other indicated treatments like ACE inhibitors or ARBs. In the second part, participants are randomly assigned to take either BI 690517 tablets or placebo tablets once daily alongside empagliflozin for the rest of the study. The placebo tablets look like BI 690517 but contain no active medicine. Participants have regular visits to the study site, about four times in the first six months, then every six months afterward. During these visits, doctors monitor kidney function, heart health, blood pressure, weight, and any side effects. Blood and urine samples are taken to track health changes. The main outcomes measured are the time until worsening kidney disease, hospitalization for heart failure, or cardiovascular death. The study ends when a certain number of these events have occurred.

Researchers are evaluating the safety and effectiveness of the Shockwave Reducer, an implantable device, for treating patients with refractory angina pectoris who continue to have symptoms despite receiving the best possible medical therapy. The study includes patients with evidence of reversible myocardial ischemia in the left coronary artery distribution who are not suitable for revascularization. Additionally, a non-randomized single-arm registry will assess the device in patients with ischemia in the right coronary artery, those without obstructive coronary disease but abnormal coronary flow reserve, and those unable to complete exercise testing due to limb amputation or mobility issues requiring walking aids. The study is a multicenter, randomized, double-blinded, sham-controlled trial with three groups. One group receives the Shockwave Reducer implant, another undergoes a sham implantation procedure without device placement, and a third group participates in a non-randomized registry receiving the device. The device is implanted in the coronary sinus, and patients continue their stable anti-anginal medication regimen. The study monitors outcomes over six months after implantation. Participants will be evaluated through various tests including stress echocardiography, nuclear imaging, PET, MRI, CT perfusion, and physiological assessments to confirm reversible ischemia. They will also undergo exercise tolerance tests, echocardiography to assess heart function, and angiography. Researchers will measure effectiveness and safety endpoints at six months. Follow-up visits and tests will ensure adherence and monitor for any adverse events. Total participation includes screening, treatment, and follow-up over at least six months.

This research aims to evaluate whether lowering blood phosphate levels in people with end-stage kidney disease (ESKD) who are on dialysis can reduce the risk of death or major heart-related events compared to maintaining higher phosphate levels. The study also looks at whether lowering phosphate improves physical health, fatigue, quality of life, patient satisfaction, and itching, as well as whether it is cost-effective. Hyperphosphatemia, or high phosphate in the blood, is common in ESKD and linked to higher death risk, but there is no strong trial evidence that lowering phosphate improves important patient outcomes. Participants will be randomly assigned to one of two groups: an intensive phosphate target group aiming to keep serum phosphate at or below 1.50 mmol/L using phosphate-lowering medications, or a liberal phosphate target group aiming for a higher phosphate range of 2.0 to 2.5 mmol/L. In the liberal group, all phosphate-lowering drugs at baseline will be stopped and only restarted if phosphate rises above 2.5 mmol/L. Medication choice and doses will be based on physicians' and participants' decisions to meet target levels. The trial is multinational and will include 3600 adults on dialysis. During the study, researchers will track major outcomes including cardiovascular death or serious heart and artery events over 5 years. They will also assess physical health, quality of life using the EQ5D-5L questionnaire, fatigue, itching, and overall survival. The study involves monitoring serum phosphate levels and medication use, and measuring cost-effectiveness of the treatment strategies. Participants will be followed closely to understand the safety and impact of the phosphate targets on their health and well-being.

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.

Aortic stenosis (AS) affects a significant portion of the elderly population, with approximately 5% of those over 65 years old and around 3% of those over 75 years having moderate to severe AS. The number of people with AS is increasing rapidly due to an aging population, creating challenges for clinicians in managing mostly elderly patients who are often symptom-free but have severe AS diagnosed incidentally. While symptomatic severe AS requires aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI), the best approach for asymptomatic patients remains unclear. This trial aims to compare early AVR or TAVI with standard expectant management in these patients to provide evidence on clinical outcomes and cost-effectiveness. The study is a large, multi-center randomized controlled trial conducted in the UK, Australia, and New Zealand, with plans to expand internationally. It includes two phases: a vanguard phase and a main phase, with an internal pilot to ensure adequate recruitment over two years. Eligible participants with severe asymptomatic AS will be randomly assigned to either early AVR or ongoing surveillance (expectant management). Those in the early AVR group will undergo surgery within about three months, which may include additional procedures like coronary angiography and possible coronary interventions if needed. The trial uses intention-to-treat analysis to compare outcomes between groups. Participants will be closely monitored throughout the study, with evaluations including routine tests and assessments as part of their care. The primary outcome measured is a combination of cardiovascular death and hospitalization for heart failure over a minimum of three years. The study also collaborates with another trial, EVoLVeD, offering participants additional research opportunities. Overall, the study seeks to provide important data on whether early valve replacement before symptoms develop can improve outcomes for people with severe asymptomatic AS.