Carshalton

Researchers are studying the effects of DMX-200 (repagermanium), a drug that blocks a receptor involved in inflammation, in people with focal segmental glomerulosclerosis (FSGS) who are also taking an angiotensin II receptor blocker (ARB). This Phase 3 trial aims to assess the safety and effectiveness of DMX-200 compared to placebo over 104 weeks in adults and adolescents aged 12 to 17 years. Following the initial study, an open-label extension will evaluate long-term safety and benefits for up to two more years. Participants will be randomly assigned to receive either DMX-200 at 120 mg twice daily or a placebo, while continuing their ARB treatment. The study includes a screening and qualification period lasting 6 to 14 weeks, a 104-week double-blind treatment phase, and a 4-week follow-up after treatment. Those completing this phase may enter the open-label extension for an additional minimum of 104 weeks, with another 4-week follow-up period, making the total study duration about 230 weeks. During the trial, participants will undergo regular assessments including urine protein and creatinine testing, kidney function monitoring by estimated glomerular filtration rate (eGFR), and safety evaluations. The main outcomes measured are changes in proteinuria, kidney function slope up to week 104, and long-term safety through week 216. Safety will be closely monitored throughout both the double-blind and extension periods to understand the drug's effects over time.

Researchers are conducting the Avacostar PASS, a multi-national, non-interventional prospective cohort study to gather data on patients with active severe ANCA-associated vasculitis (AAV). The study compares two groups: patients treated with avacopan and those treated with cyclophosphamide or rituximab-based induction regimens without avacopan. The goal is to evaluate the incidence of specific medical events of special interest (MESIs) over a long-term period. The study is planned to last up to 7 years, including about 3 years for recruitment. Participants will be enrolled in Germany, the United Kingdom, and possibly other countries depending on avacopan availability and suitability. Patients starting induction treatment with avacopan or standard care within 6 months prior to enrollment may join the study. Data will be collected prospectively, with some retrospective data allowed if needed. Follow-up will continue for each patient until 4 years after the last participant is enrolled, with periodic data collection at routine clinic visits. During the study, researchers will collect data on participants' medical status, treatment, and safety events to monitor the incidence of MESIs. The primary outcome focuses on safety monitoring related to avacopan use in AAV. Participants will be observed regularly through their usual clinical care visits, ensuring ongoing assessment of treatment effects and safety over several years.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) affects millions worldwide and is a leading cause of kidney failure. This research aims to evaluate whether metformin, a common diabetes medication, can be repurposed to slow kidney function decline in adults with early-stage ADPKD. The trial addresses the limited treatment options currently available and the significant impact of ADPKD on quality of life, anxiety, and depression. Participants will be randomly assigned to receive either extended-release metformin or a placebo with inactive tablets identical in appearance. This global Phase III study plans to enroll 1,174 adults aged 18 to 70 years diagnosed with ADPKD. The study will carefully monitor kidney function over 24 months to assess the effects of metformin on disease progression. During the study, participants will undergo evaluations including kidney function tests measured by estimated glomerular filtration rate (eGFR). Researchers will track changes over two years to determine if metformin slows kidney decline. Safety assessments and adherence monitoring will also be part of the study to ensure participant well-being throughout the trial period.

Researchers are evaluating VX-147 for its effectiveness, safety, tolerability, and how the body processes it in adults and children aged 10 to 65 who have apolipoprotein L1 (APOL1)-mediated proteinuric kidney disease. This study is a Phase 2/3 trial designed to better understand treatment options for this specific kidney condition. Participants will receive either VX-147 or a placebo, both given as oral tablets. The study is double-blind and placebo-controlled, meaning neither participants nor researchers know who receives the active drug or placebo during the treatment period. The trial consists of two parts: Part A focuses on treatment effects over at least 48 weeks, while Part B involves continued safety and tolerability observation for approximately four years after the last participant enrolls. Throughout the study, participants will undergo regular assessments including measurements of urine protein to creatinine ratio and kidney function via estimated glomerular filtration rate (eGFR). Safety is monitored by tracking adverse events and serious adverse events. Data will be collected during the treatment period and followed long-term to evaluate both efficacy and safety outcomes, with some measures assessed at interim and final analyses over at least two years.

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 studying how to improve the accuracy of MRI scans in identifying early-stage rectal cancer and significant rectal polyps. Early-stage rectal cancers grow partially into the bowel wall and can often be treated with local procedures that preserve the bowel, avoiding major surgery and its risks. Many patients are currently over-treated due to inaccurate MRI staging, leading to unnecessary major surgery or radiotherapy. The study focuses on a new MRI reading method called PRESERVE that has shown higher accuracy in identifying early rectal cancers suitable for local excision. The study involves training radiologists across 20 hospitals in the PRESERVE MRI reading method to better stage early rectal cancers and significant polyps. MRI scans are recommended before removal of rectal polyps that are 20mm or larger or have features suspicious for cancer. Radiologists will be trained to use the PRESERVE system to improve diagnostic accuracy and help guide treatment choices, aiming to increase the number of patients offered organ-preserving surgery. Participants will be monitored by comparing MRI reports before and after the radiologist training over one year. Researchers will measure the impact of the training on the accuracy of tumor staging and whether more patients receive local procedures instead of major surgery. This study will help determine if the new approach can be widely adopted to improve patient outcomes and preserve quality of life.

Researchers are evaluating whether stopping regular non-invasive screening for coronary artery disease (CAD) after kidney transplant waitlist activation is not worse than continuing regular annual or biennial screening. The study focuses on preventing major heart-related events in adults on dialysis awaiting kidney transplantation. This trial aims to clarify if routine CAD screening improves outcomes or if it can be safely omitted, potentially reducing harms and costs associated with current screening practices. Participants will be divided into two groups: one will receive no further CAD screening after joining the transplant waitlist, while the other will continue with regular screenings every one to two years. Both groups will be followed for up to 72 months, including 12 months after transplantation, to monitor heart-related events and transplantation rates. The study will also compare the cost-effectiveness of stopping versus continuing screening. During the trial, participants will undergo evaluations to track the time until their first major adverse cardiac event. Researchers will collect data on heart health, transplant outcomes, and healthcare costs throughout the study period. Participants are expected to be monitored for up to five years post-enrollment to understand the long-term impact of different screening strategies.

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.

People with a leg injury treated with a plaster cast or splint face an increased risk of blood clots, which can cause serious health problems or death. This research aims to evaluate the clinical and cost effectiveness of different blood clot prevention methods for such patients, including tablets versus injections, especially for those at high risk of clots. The study includes two linked trials, TiLLI-High and TiLLI-Low, to determine if tablets are as effective as injections for high-risk patients and whether any medication benefits low-risk patients. Participants who have had a leg injury and are immobilized with a rigid cast or brace will be assessed for their risk of blood clots. High-risk participants will be randomly assigned to receive either daily tablets (Rivaroxaban 10mg once daily or Apixaban 2.5mg twice daily) or daily injections (Enoxaparin, Tinzaparin, Dalteparin, or Fondaparinux at specified doses). Low-risk participants will be randomized to tablets, injections, or no medication. Treatment lasts for the duration of immobilization or up to 42 days, whichever is shorter, following current guidelines. Participants will be followed for 90 days after starting treatment to monitor for blood clots, bleeding, or related complications. Data will be collected through medical records and participant contact without requiring extra hospital visits. The study also includes safety monitoring by an independent panel and aims to provide valuable information on treatment effectiveness, patient comfort, and healthcare costs to inform future care guidelines.

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.