Gralum

Researchers are conducting a phase III randomized, open-label, multicenter trial across several countries including Sweden, Norway, Finland, Denmark, Italy, Australia, and New Zealand. The study focuses on elderly patients with untreated diffuse large B-cell lymphoma (DLBCL), defined as patients aged 80 years or older, or those aged 75 years or older who are considered frail based on a simplified Comprehensive Geriatric Assessment. The trial aims to compare the effectiveness of two treatment regimens in this population. Participants are randomly assigned to receive either the standard R-miniCHOP treatment or an experimental R-pola-miniCHP regimen where vincristine is replaced with an immunoconjugate, polatuzumab vedotin. Both treatments involve cycles of drugs including rituximab, cyclophosphamide, doxorubicin, and prednisone, administered over 18 weeks. The trial includes a screening period lasting up to 4 weeks, followed by the active treatment phase, and then a follow-up period lasting up to 36 months after treatment completion. Throughout the study, participants will be monitored to measure progression-free survival over 2 years as the primary outcome. The study involves regular assessments including clinical evaluations and safety monitoring. Enrollment began in the first quarter of 2020, with the last patient visit expected by the first quarter of 2027, allowing for long-term observation of treatment effects and patient outcomes.

Immunoglobulin A nephropathy (IgAN) is a kidney disease caused by the build-up of immune protein complexes in the kidneys, leading to inflammation and possible kidney damage. This Phase 3 study is evaluating how well mezagitamab, compared to a placebo, reduces protein levels in the urine (proteinuria) in adults with primary IgAN. It also aims to assess the safety and tolerability of mezagitamab and its ability to maintain kidney function over the long term. Participants will be randomly assigned to one of two groups in the main study: two-thirds will receive mezagitamab injections under the skin, and one-third will receive placebo injections that look identical but have no active medicine. Treatment will occur in two 1-year cycles, each including about six months of dosing and six months of observation with monthly check-ups. An open-label group will include a small number of participants with lower proteinuria or kidney filtering issues, including those who previously received mezagitamab in another study; these participants will receive mezagitamab similarly to the main group. During the study, participants will visit the clinic several times for assessments. Researchers will monitor changes in proteinuria from the start through week 36, along with safety and kidney function. They will also perform regular evaluations and check-ups throughout each treatment and observation period to track participants' health and response to treatment.

Researchers are investigating the safety and effectiveness of pirtobrutinib in adults with Primary Immune Thrombocytopenia (ITP), a condition where the immune system attacks platelets. This study includes a phase 1 dose-escalation to assess tolerability and side effects, followed by a phase 2 dose-optimization to compare different doses of pirtobrutinib against a placebo. The goal is to understand how well pirtobrutinib works and how safe it is for this condition. Participants will receive study drug orally, either pirtobrutinib or a placebo. The phase 1 portion lasts up to 16 weeks focusing on dose escalation, while the phase 2 portion lasts up to 28 weeks for dose optimization. Blood tests will be done to measure drug levels in the bloodstream and monitor elimination. The study excludes the initial screening period. Throughout the study, participants will have various assessments including monitoring of vital signs, laboratory tests, electrocardiograms, and evaluation of any adverse effects. The primary outcomes are safety-related events during the first 4 to 16 weeks and efficacy compared to placebo up to 24 weeks. The total study duration for participants varies based on their assigned phase and treatment group, with careful monitoring of safety and treatment responses.

Researchers are evaluating whether the medicine tenecteplase helps adults recover from an acute ischemic stroke when given more than 4.5 hours after they were last seen well. This study focuses on people who had a stroke caused by a clot blocking blood flow in the brain and who have imaging showing brain tissue that can still be saved. Participants should not be planning to receive a procedure to remove the clot and must have a pre-stroke disability level of 0 or 1 on the modified Rankin Scale. Participants are randomly placed into two groups. One group receives a single injection of tenecteplase into a vein, while the other group receives standard medical care. The study includes adults aged 18 and over who had an acute stroke or woke up with stroke symptoms more than 4.5 hours ago. Imaging with MRI or CT is used to confirm eligibility. The study lasts about three months, starting with a hospital stay of about one week. During the study, participants have seven clinical examinations or visits to monitor their recovery and health. The last two visits may be done from home to allow remote assessments. Researchers use the modified Rankin Scale to measure disability or dependence in daily activities at 90 days after treatment. They also monitor for any side effects or health changes to compare the effects of tenecteplase against standard care.

Researchers are evaluating the safety and effectiveness of stopping antibiotic treatment early in adult patients hospitalized with respiratory virus infections. This study addresses concerns about antibiotic overuse in community-acquired pneumonia, which can lead to resistance. The trial focuses on patients with moderately severe disease who test positive for respiratory viruses like influenza, RSV, and others, aiming to see if stopping antibiotics early is as safe and effective as continuing them. Participants are adults 18 years or older who are already on antibiotics started by their admitting doctor. They will be randomly assigned to either stop antibiotic therapy or continue it as usual. The main goal is to compare early clinical response at 120 hours after randomization, defined by survival with symptom improvement without needing additional antibiotics. The study also looks at mortality rates, length of hospital stay, and total antibiotic use. During the study, researchers will monitor symptoms, treatment needs, and patient outcomes closely. They will track improvements or worsening of symptoms and record any additional treatments required. The involvement period includes hospitalization and follow-up through the early clinical response time point. Safety and treatment effects will be assessed carefully to determine if early antibiotic discontinuation is a viable option.

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 evaluating whether Negative Pressure Wound Therapy (NPWT) is more effective, less effective, or equally effective compared to standard wound care for patients with diabetic foot ulcers (DFUs). The study focuses on important questions such as differences in the number of major amputations, the need for additional surgeries, and length of hospital stays during the first year after treatment. This trial addresses a serious complication of diabetes, as up to 34% of diabetic patients develop DFUs, which often lead to amputations and carry high risks of mortality and reduced quality of life. Participants will be randomly assigned to receive either NPWT or standard wound care following surgical treatment of their diabetic foot ulcers. NPWT involves using a sealed system that applies controlled suction to the wound to promote healing, with dressings changed every 3 to 5 days until the wound shows healthy granulation tissue. The standard wound care group receives moist wound dressings with daily inspections and changes, progressing to specialized antibacterial or hydrophobic dressings as healing advances. Both groups will receive antibiotics based on microbiological cultures and support for swelling with compression therapy. Throughout the study, participants will be closely monitored for one year after treatment. Researchers will collect data on the number of lower extremity amputations, wound healing, hospital stays, and patient-reported outcomes. Adverse events, including serious complications like infections or cardiovascular events, will be tracked carefully. The study aims to improve treatment recommendations for diabetic foot ulcers, reduce severe complications, and lower healthcare costs by determining the best wound care approach.

Researchers are investigating whether the medicine vicadrostat, when taken together with empagliflozin, can lower the risk of heart-related problems in adults who have type 2 diabetes, high blood pressure, and cardiovascular disease but no history of heart failure. This study is a Phase III trial that compares the effects of vicadrostat plus empagliflozin to a placebo plus empagliflozin in people with these conditions. Participants are randomly assigned to one of two groups: one group takes vicadrostat and empagliflozin tablets, and the other group takes placebo tablets that look like vicadrostat along with empagliflozin. All participants take one tablet daily for a period ranging from two and a half years up to four years and three months. Throughout the study, participants continue their usual medications for diabetes, high blood pressure, and cardiovascular disease. During up to 51 months of participation, participants visit the study site regularly where doctors collect health information and blood samples. Researchers track when participants experience cardiovascular events such as heart-related deaths or heart failure events. The study also monitors participants’ overall health and any side effects they may experience to assess the safety and effects of the treatments.

Researchers are evaluating the effects of three different treatments on major adverse kidney events (MAKE) in adults who are unconscious after being resuscitated from out-of-hospital cardiac arrest. This sub-study is part of the larger STEPCARE trial and involves 3,500 participants. The study focuses on kidney-related outcomes, including death within 30 days, need for kidney replacement therapy, and kidney function changes measured by creatinine levels at hospital discharge. The main trial randomly assigns patients to one of three treatments: continuous deep sedation for 36 hours versus minimal sedation; fever control using a feedback-controlled device if body temperature rises above 37.7°C versus fever control without a device; and two blood pressure targets with mean arterial pressure (MAP) set to either ≥65 mmHg or ≥85 mmHg maintained by vasopressors for 36 hours. The feedback-controlled temperature device is set to maintain temperature at 37.5°C when used. Participants will be closely monitored during their hospital stay with data collected prospectively according to the main trial protocol. Researchers will assess major adverse kidney events within 30 days and examine creatinine changes during the hospital stay and within 72 hours after resuscitation. The study aims to understand how these treatments affect kidney outcomes after cardiac arrest, with analyses following a predefined statistical plan.

This research aims to determine if a home-based exercise program called "five plus training" can improve walking ability more than the usual recommendation of walking daily for patients with intermittent claudication, a condition causing pain in the calf muscles due to reduced blood flow. The study focuses on patients who experience calf pain after walking short distances and evaluates the impact of different exercise approaches on their walking capacity and quality of life. Participants will be randomly assigned to one of two exercise groups: one group will follow the "five plus training," which involves standing and lifting the body onto tiptoes repeatedly until calf pain begins, then performing five additional lifts; the other group will walk for at least 30 minutes three times per week. The "five plus training" is done three times a day using a wall for balance support. These exercises aim to induce muscle ischemia followed by reperfusion to maximize training effects. During the 12-week study, researchers will assess participants' walking distance on a treadmill and use questionnaires to measure quality of life. They will also monitor blood flow using the Ankle-Brachial index. The study includes regular follow-ups to evaluate how each exercise program affects walking ability and overall well-being in patients with intermittent claudication.