Gillingham

Researchers are evaluating two different methods of pacing the heart in patients with slow heart rates (bradycardia). This multi-center randomized controlled trial, called PROTECT-HF, aims to compare the standard right ventricular pacing approach with a newer physiological pacing technique, which includes His bundle and left bundle area pacing. The study will enroll 2600 patients to assess differences in outcomes related to heart function and survival. Participants will be randomly assigned to receive either right ventricular pacing or physiological pacing through pacemaker implantation. The physiological pacing method may involve His bundle pacing or left bundle pacing, with biventricular pacing used if these are not possible. Both treatments will be performed at participating centers, with patients and outcome assessors blinded to the treatment allocation. A subgroup of 500 patients will also take part in an optional echocardiographic sub-study to observe heart changes over 24 months. During the study, participants will be monitored from the time of consent for up to 78 months. Evaluations will occur at the start and every six months afterward to track mortality and heart failure-related health events. Researchers will gather data on heart function, treatment effects, and safety. The main analysis will consider all patients as originally assigned, and additional analysis will assess those who received the assigned treatment.

Migraine is a condition that often causes moderate to severe headaches on one side of the head, sometimes with throbbing pain, nausea, vomiting, and sensitivity to light and sound. This study evaluates the safety and effectiveness of atogepant, a medicine approved for preventing migraines in adults, to see how well it works compared to placebo in preventing chronic migraines in participants aged 12 to 17 years. The study is a phase 3, double-blind trial where neither the participants nor the doctors know who receives the medicine or placebo. Participants will be randomly assigned to receive either oral atogepant tablets or placebo tablets once daily for 12 weeks. Following the treatment period, there will be a 4-week follow-up phase. The study involves about 420 participants at approximately 70 sites worldwide. Throughout the study, participants will visit hospitals or clinics regularly to complete daily diaries, undergo medical assessments and blood tests, report any side effects, and complete questionnaires. Researchers will measure the number of participants experiencing adverse events and track changes in the average monthly number of migraine days from the start of the study through week 12.

Researchers are evaluating the safety and effectiveness of low-dose and high-dose atogepant in children and adolescents aged 6 to 17 who experience episodic migraine. Migraines are moderate to severe headaches often accompanied by symptoms such as throbbing pain, nausea, and sensitivity to light and sound. While several treatments exist for adults, options for younger patients are limited, making this Phase 3 study important to understand how atogepant works in this younger population. Participants aged 6 to 17 will be randomly assigned to one of six groups to receive either placebo, low-dose atogepant, or high-dose atogepant tablets taken once daily by mouth for 12 weeks. The exact doses for children aged 6 to 11 will be decided after a pharmacokinetic substudy. After 12 weeks, participants may either have a follow-up visit 4 weeks after stopping the treatment or join an extension study to continue taking atogepant for an additional 52 weeks. During the study, participants will attend regular visits at hospitals or clinics for medical assessments, blood tests, and to monitor for any side effects. They will also complete questionnaires to evaluate how treatment affects their migraines. The main outcomes measured are changes in the number of monthly migraine days over 12 weeks and the number of participants experiencing adverse events during the first 16 weeks. About 450 participants will be enrolled across roughly 100 sites worldwide.

Researchers are evaluating the safety and effectiveness of whole-body hypothermia treatment in newborn babies diagnosed with mild hypoxic ischaemic encephalopathy (HIE). This phase III randomized controlled trial aims to determine whether cooling babies to 33.57b0C within six hours of birth for 72 hours improves cognitive development at two years of age compared to maintaining normal body temperature (normothermia). The study also assesses the cost-effectiveness of cooling therapy to help guide national and international treatment guidelines and standardize care across the NHS. Babies born at or after 36 weeks with specific signs of birth asphyxia or acidosis are randomly assigned to either whole-body hypothermia or targeted normothermia groups. The hypothermia group will have their body temperature lowered and maintained at 33.57b0C using a cooling machine for 72 hours in a neonatal intensive care unit. The normothermia group will have their temperature maintained at 377b0C with treatment for any fever using standard protocols. If babies in the normothermia group develop seizures and worsen to moderate HIE, they may receive cooling treatment as part of clinical care. Conventional MRI scans will be performed before discharge. Participants will be followed up at 24 months of age (7 months) using the Bayley Scales of Infant and Toddler Development IV to measure cognitive, language, and motor skills. Additional neurological exams, including assessments for cerebral palsy, vision, and hearing, will be conducted. Parents will complete questionnaires about their child's development. Researchers will collect detailed clinical data from birth through follow-up to evaluate safety and developmental outcomes. Babies who die or cannot complete assessments due to severe disability will be assigned specific scores to reflect outcomes.

Researchers are evaluating two surgical approaches for patients with low risk differentiated thyroid cancer in this multi-center, randomized, phase III study. The study aims to determine if hemithyroidectomy, which removes part of the thyroid, is an acceptable and cost-effective alternative to total thyroidectomy, which removes the entire thyroid. Patients are identified through oncology multidisciplinary team meetings and divided into two groups based on their treatment history and diagnosis method. Patients in Group 1 have already had a hemithyroidectomy for thyroid problems and are then diagnosed with low risk differentiated thyroid cancer. They will be randomized to either surveillance only or a second surgery to remove the rest of the thyroid gland (two-stage total thyroidectomy). Group 2 patients are diagnosed by cytology with low risk cancer and have not yet had surgery; they will be randomized to either hemithyroidectomy or a single-stage total thyroidectomy. The study plans to recruit 456 patients who will be followed after surgery and then every 12 months for 6 years. During the study, participants will undergo regular assessments to monitor for any signs or symptoms of cancer recurrence, with a primary outcome measure of the 3-year recurrence rate after surgery. Follow-up visits will include clinical evaluations to check for cancer return or progression. Researchers will also observe overall patient outcomes and safety throughout the 6-year follow-up period.

Researchers are evaluating the use of biparametric MRI (bpMRI) and image-fusion targeted biopsies to detect prostate cancer in men at risk. The study aims to determine if bpMRI can be recommended as an alternative to the longer multiparametric MRI (mpMRI) for identifying clinically significant prostate cancers. It also compares image-fusion targeted biopsy with visual-registration targeted biopsy to see which method better detects significant prostate cancer in patients with suspicious MRI findings. Participants will undergo one of two types of MRI scans: a longer 30-40 minute MRI that uses a contrast dye called gadolinium (commonly used in the NHS), or a shorter MRI without contrast. If the MRI shows suspicious areas, participants may then have a prostate biopsy. Biopsies are performed either by visual registration, where the biopsy needle placement is guided by the operator’s judgment using MRI and ultrasound images, or by image fusion, where MRI images are overlaid on live ultrasound using software to guide the biopsy needle more precisely. During the study, patient scans and biopsy results will be closely monitored and analyzed to measure how many clinically significant cancers are detected within 12 weeks of enrollment. Researchers will collect MRI images, perform biopsies if indicated, and evaluate the biopsy samples under a microscope. The study includes safety monitoring and aims to inform future NHS practices for prostate cancer diagnosis. Male participants aged 18 and older who are referred for prostate MRI due to abnormal exams or elevated PSA levels are eligible to join.

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.

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.

Researchers are evaluating if using additional liver diffusion weighted MRI (DW-MRI) scans at diagnosis can find more synchronous liver metastases than CT scans alone in patients with high risk colorectal cancer. This phase II multicenter study focuses on patients with advanced primary colorectal tumors who have no evidence of liver metastases on CT scans. The goal is to improve detection and management of liver metastases by sharing MRI findings with multidisciplinary teams for treatment decisions. Participants will undergo additional breath hold T1, T2, and DW-MRI liver scans without intravenous contrast every six months for three years after surgery. Any liver metastases detected on these scans will be reviewed by the local multidisciplinary team and treated following local protocols. This ongoing monitoring aims to identify metastases early and guide appropriate therapy. During the study, participants will have regular imaging assessments and clinical evaluations as part of their post-surgery surveillance. The researchers will measure the presence of liver metastases through these MRIs and track treatment responses. Findings will be discussed in multidisciplinary team meetings, and participants will be followed for five years after the last recruitment to assess long-term outcomes and management of liver metastases.

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.