Karlstad

Researchers are investigating ways to personalize treatment for patients with head and neck squamous cell carcinoma HNSCC, especially those with advanced disease who face a higher risk of treatment failure. This phase III study compares two radiotherapy approaches for patients intended for curative treatment the standard radiotherapy and a hyperfractionated radiotherapy HFX-RT with a higher total radiation dose. The study also aims to improve prognostic and predictive methods by including exploratory analyses such as MRI to evaluate tumor hypoxia, gene profiling, immune profiling, and imaging texture analyses during treatment and follow-up. Participants will be randomly assigned to either standard radiotherapy, which delivers 68.0 Gy in daily fractions of 2.0 Gy, or to hyperfractionated radiotherapy, which delivers 83.0 Gy in smaller doses twice daily 1.22 Gy per fraction over five days per week. The doses vary depending on the tumor volume and lymph node involvement. Patients with lower-risk tumors not eligible for randomization may still participate in the translational research parts of the study. During the study, participants will be closely monitored with regular follow-up visits every three months for two years, then every six months up to five years, focusing on local tumor control. Researchers will collect imaging data, conduct gene and protein analyses, and assess tumor response. The study evaluates treatment effects and tumor behavior over time to better understand and improve outcomes for head and neck cancer patients.

Researchers are evaluating the combination of baxdrostat and dapagliflozin in people with chronic kidney disease CKD and high blood pressure hypertension. This Phase III, double-blind, placebo-controlled study aims to assess whether this combination reduces the risk of serious kidney damage, heart failure events, or cardiovascular death compared to dapagliflozin alone. The study includes participants with CKD and hypertension who meet specific kidney function and blood pressure criteria. Participants who are not already taking SGLT2 inhibitors will first complete a 4-week dapagliflozin run-in period. Then, they will be randomly assigned to receive either baxdrostat plus dapagliflozin or a placebo plus dapagliflozin. Baxdrostat dosing may start low and be increased if needed. Study visits will occur at 2, 4, 8, 16, 34, and 52 weeks after randomization, and then approximately every four months until the study ends, which is based on the number of key kidney or heart-related events. Throughout the study, participants will have regular assessments including blood tests to monitor kidney function and potassium levels, blood pressure measurements, and evaluations of heart and kidney health. If participants stop the blinded study drug early, they will continue dapagliflozin if possible and remain in the study for ongoing visits and monitoring. The main outcome is whether the combination treatment reduces the risk of a 50% sustained decline in kidney function, kidney failure, heart failure events, or cardiovascular death over up to 37 months.

Researchers are investigating whether regular radiological assessments during follow-up after surgery for high-risk malignant melanoma improve patient survival. The study addresses concerns about the resource demands, potential radiation exposure, and anxiety caused by such imaging, especially given the recent introduction of effective medical treatments for melanoma. There is currently no clear evidence supporting routine imaging in this context. Participants are randomly assigned to one of two groups. One group follows national guidelines with regular doctor appointments for 3 years, while the other group receives the same follow-up plus additional whole-body CT or PET scans and blood tests at baseline, 6, 12, 24, and 36 months. An interim analysis will be done after 1,000 patients enroll. During the study, researchers will monitor overall survival at 5 years as the primary outcome. They will also assess quality of life through questionnaires over the 3-year follow-up. Participants will attend scheduled visits for clinical evaluations, imaging, and blood tests, with the study aiming to provide clear evidence about the role of imaging in post-surgical melanoma care.

Researchers are evaluating nipocalimab, a drug given intravenously or subcutaneously, for adults with generalized myasthenia gravis gMG, a condition causing muscle weakness. This Phase 3 study aims to compare the effectiveness and safety of nipocalimab against a placebo and to understand how the drug works in the body when given by injection under the skin versus through a vein. The study includes a subcutaneous substudy to explore these differences in delivery methods. Participants receive nipocalimab intravenous infusions every two weeks for up to 24 weeks during a double-blind placebo-controlled phase. Those completing this phase can enter an open-label extension, choosing to continue receiving intravenous nipocalimab or switch to the subcutaneous form given weekly for eight weeks, with the option to continue longer in a long-term extension. Placebo is also given intravenously every two weeks in the control group during the double-blind phase. Throughout the study, participants undergo regular assessments including muscle function scores, quality of life evaluations, and blood tests measuring antibody levels and drug concentration. Researchers monitor safety by tracking adverse events and changes in clinical and laboratory parameters. The study measures changes in activities of daily living related to myasthenia gravis over time. Participation may last several years, as long-term monitoring continues after the initial treatment phases to evaluate ongoing effects and safety.

Researchers are evaluating whether a shorter period of immunotherapy after radical surgery is as effective as the standard longer treatment for patients with high-risk malignant skin melanoma. This study focuses on people aged 18 and older who have undergone surgery for stage IIb-c, III, or IV melanoma. The goal is to see if six months of immunotherapy can prevent cancer recurrence as well as the current 12-month treatment, potentially reducing side effects, hospital visits, and healthcare costs. The study is a randomized phase 3 trial conducted internationally with patients followed for up to five years. Participants will receive immunotherapy drugs, currently nivolumab or pembrolizumab, given intravenously. They are randomly assigned to either six months experimental group or 12 months standard group of treatment. Patients who had immunotherapy before surgery neoadjuvant treatment can also join, with their pre-surgery treatment time added to the post-surgery treatment. Medical exams and imaging scans CT or PET-CT are done at the start, six months, and 36 months, along with regular check-ups over three years. If cancer returns, additional tests and treatments are planned based on medical team decisions. During the study, participants will have scheduled visits for physical exams, blood tests, and scans to monitor their health and detect any recurrence. Researchers will measure relapse-free survival and distant metastatic-free survival at two years as primary outcomes, with overall survival and health economic effects also assessed over five years. Safety monitoring includes standard care practices and follow-up for up to five years. The study aims to confirm if shorter immunotherapy duration maintains the same outcomes while benefiting patients and healthcare systems.

Robotic-assisted laparoscopic surgery is increasingly used, especially for older and more fragile patients who may not tolerate major open surgery. This research focuses on the challenges to heart function during robotic surgery involving a steep 30-degree head-down tilt Trendelenburg position, which can increase the hearts workload. The study compares patients with normal heart function to those with systolic heart failure under these conditions to understand circulatory effects better. Participants undergo preoperative echocardiography to classify heart function as normal or decreased ejection fraction 45% or lower. During surgery, heart performance is monitored using an esophageal doppler device, while brain oxygen levels are measured by optical spectrophotometry. Measurements are taken before anesthesia, during Trendelenburg positioning, at the start of the pneumoperitoneum carbon dioxide insufflation, and after returning to a flat position. Throughout the study, standard anesthesia parameters and various cardiac output measures are recorded to analyze heart workload changes. The main outcome is the change in stroke volume during Trendelenburg positioning and pneumoperitoneum within 15 minutes. Secondary outcomes include changes in systemic vascular resistance, pulse pressure variation, peak velocity, stroke volume variation, flow time corrected, and regional brain oxygen saturation. This observational study helps identify which patients may be at risk of heart complications during robotic surgery and informs safer surgical decisions.

Researchers are studying patients who experience out-of-hospital cardiac arrest OHCA with ventricular fibrillation VF or ventricular tachycardia VT that do not respond to initial defibrillation. The study aims to evaluate whether using double sequential defibrillation DSD earlier, after the first failed standard defibrillation, can improve 30-day survival compared to continuing with standard defibrillation. This trial addresses important gaps in knowledge about optimal defibrillation strategies to increase survival in this critical condition. The trial compares two treatment groups one using early double sequential defibrillation, where a second defibrillator with pads placed in the anterior-posterior position is applied as soon as possible, delivering rapid sequential shocks from two devices and the other continuing with standard single defibrillation using one defibrillator with anterior-lateral pad placement. Both groups receive resuscitation until return of spontaneous circulation, resuscitation is stopped, or the patient is transported to the hospital. The study is randomized and open-label, involving ambulance units equipped with two study-specific defibrillators. Participants are adult OHCA patients with an initial shockable rhythm and at least one failed standard defibrillation. During the study, ambulance teams perform screening, randomization, treatment according to assigned group, and initial follow-up. The main outcome measured is survival at 30 days. Secondary outcomes include return of spontaneous circulation, survival to hospital admission and discharge, and neurological function at discharge. The study will continue monitoring these outcomes to assess the effectiveness of early DSD compared to standard defibrillation strategies.

Researchers are evaluating the effects of vicadrostat combined with empagliflozin in adults who have type 2 diabetes, high blood pressure, and cardiovascular disease but no history of heart failure. The study aims to assess whether this combination can help reduce cardiovascular risks compared to a placebo with empagliflozin. This Phase III trial involves adults with these conditions who are already receiving treatment for them. Participants are randomly assigned to one of two groups. One group takes vicadrostat and empagliflozin tablets daily, while the other group takes placebo tablets that look like vicadrostat but have no active medicine, alongside empagliflozin. Treatment lasts from two and a half years up to four years and three months. All participants continue their usual medications for diabetes, blood pressure, and heart disease during the study. Throughout the study, lasting up to four years and three months, participants visit the study site regularly for health checks and blood samples. Doctors monitor cardiovascular events and any side effects experienced. The main outcome measured is the time until the first cardiovascular death or heart failure event. Other health indicators like blood pressure and kidney function are also tracked to understand the effects of the treatment combination.

Researchers are evaluating the effectiveness and safety of a new oral cladribine formulation in adults with Generalized Myasthenia Gravis gMG. This phase 3 clinical trial compares cladribine to a placebo to understand its sustained benefits, the need for retreatment, and long-term safety. The study also includes a component to analyze how the drug is processed in the body and features interviews to learn about participants experiences with cladribine treatment. The trial is organized into three periods a double-blind placebo-controlled DBPC period where participants receive either placebo or cladribine in two separate oral courses a blinded extension BE period where initial placebo recipients switch to cladribine doses and some receive retreatment if needed and a retreatment RT period where participants may receive additional cladribine or placebo based on clinical need. Doses include low and high oral cladribine, administered as scheduled treatment courses. Participants will undergo various assessments including evaluations of muscle weakness and daily living activities using specific scales like the MG-ADL and QMG. Researchers will monitor safety through tracking adverse events, laboratory tests, and heart monitoring. Pharmacokinetic blood sampling will measure cladribine levels at multiple time points. The study duration extends up to week 144, during which participants responses and safety are closely observed to understand the drugs effects over time.

Researchers are evaluating the effectiveness and safety of masitinib combined with riluzole compared to a placebo combined with riluzole for treating Amyotrophic Lateral Sclerosis ALS. This phase 3 study focuses on patients diagnosed with probable or definite ALS, aiming to understand how masitinib, a drug that targets cells involved in neuroinflammation, might slow disease progression and affect the nervous systems environment. Participants receive oral masitinib at 3.0 mgkgday twice daily, with dose increases to 4.5 mgkgday after 4 weeks, and for some, an additional increase to 6.0 mgkgday after another 4 weeks. Each dose increase includes safety monitoring. Masitinib is given alongside riluzole, a standard ALS treatment at 50 mg twice daily. The control group receives a matching placebo with riluzole. The study is randomized, double-blind, and includes two different masitinib dose escalation schedules. During the 48-week study period, participants undergo regular assessments including functional rating scales ALSFRS-R, quality of life questionnaires ALSAQ-40, survival and progression monitoring, lung function tests FVC, and muscle strength measurements HHD. Researchers measure changes in combined function and survival scores. Safety is closely monitored throughout, with follow-up extending up to 36 months for disease progression or death. Total participation includes baseline screening, treatment, and long-term observation.