Karlstad

Researchers are studying head and neck squamous cell carcinoma (HNSCC) patients with factors that increase the risk of treatment failure. The goal is to personalize treatment and improve outcomes for those receiving curative radiotherapy. This phase III trial compares the standard radiation dose to a higher dose given more frequently (hyperfractionated radiotherapy) to see if intensifying treatment benefits patients with advanced disease. The study also explores advanced imaging and genetic tests to better predict treatment response and cancer behavior. Participants will be randomly assigned to receive either the standard radiotherapy dose of 68.0 Gy in 34 fractions once daily or a higher hyperfractionated dose of 83.0 Gy in 68 fractions given twice daily over five days a week. Different radiation doses are targeted to the primary tumor and affected lymph nodes based on risk areas. The trial includes translational research using MRI, CT, and PET scans, as well as gene and protein analyses, to understand tumor characteristics and treatment effects. Patients with lower-risk tumors not eligible for randomization can still join the research parts that do not involve altered radiation schedules. During the study, participants will undergo regular monitoring including imaging and clinical assessments every three months for two years, then every six months up to five years to check local tumor control. Researchers will collect data from these visits along with tissue and blood samples for genetic and immune profiling. Safety, treatment adherence, and long-term outcomes will be closely followed to evaluate the impact of the different radiotherapy approaches and the predictive value of the biological tests.

Researchers are investigating the effectiveness, safety, and tolerability of combining baxdrostat with dapagliflozin compared to dapagliflozin alone in people with chronic kidney disease (CKD) and high blood pressure. This Phase III, international, multicenter, double-blind, placebo-controlled study aims to see if this combination reduces risks such as significant kidney function decline, kidney failure, heart failure events, or cardiovascular death. The study includes a 4-week run-in period where participants not previously treated with SGLT2 inhibitors receive dapagliflozin alone. After this, participants are randomly assigned to receive either baxdrostat plus dapagliflozin or placebo plus dapagliflozin in a double-blinded manner. Study visits occur frequently initially (at 2, 4, 8, 16, 34, and 52 weeks after randomization) and then approximately every 4 months. If participants stop the blinded treatment early, they continue dapagliflozin alone unless specific criteria require its discontinuation. Participants will undergo regular assessments including blood pressure monitoring and laboratory tests related to kidney function and cardiovascular health. The primary outcome measures the reduction in risk of major kidney and heart events over up to 37 months. Even if participants stop the study treatment, they will continue follow-up visits and data collection to ensure comprehensive safety and efficacy evaluation throughout the study duration.

Researchers are investigating whether adding regular radiological scans during follow-up after surgery for high-risk malignant melanoma improves patient survival. This study focuses on patients who have undergone radical surgery for stage IIb-c and III cutaneous malignant melanoma. Since radiological exams can be costly, cause anxiety, and expose patients to radiation, the study aims to determine their value especially given the availability of effective medical treatments for melanoma. Participants are randomly assigned to one of two groups for a 3-year follow-up period. One group receives routine follow-up with regular doctor visits according to national guidelines. The other group receives the same follow-up plus whole body CT or PET scans and blood tests at baseline, 6, 12, 24, and 36 months. An interim analysis will be done after 1000 patients have enrolled. Throughout the study, researchers will monitor overall survival over a 5-year period. Participants will have scheduled assessments including scans and blood tests if assigned to the imaging group. The study also tracks adherence to follow-up visits and any health changes. This approach aims to provide clear evidence on the benefit and impact of imaging during follow-up after melanoma surgery.

Researchers are evaluating the effectiveness and safety of nipocalimab compared to placebo in adults with generalized myasthenia gravis (gMG), a condition causing muscle weakness. This phase 3, multicenter, randomized, double-blind study also includes a subcutaneous substudy to assess how nipocalimab works in the body when given as an injection under the skin compared to intravenous infusion. Participants will receive nipocalimab or a matching placebo through intravenous infusion. In the subcutaneous substudy, nipocalimab will be administered under the skin. The study includes groups receiving different forms of the drug, with dosing schedules detailed in the protocol. The subcutaneous substudy requires participants to maintain stable doses of corticosteroids and/or immunosuppressants for the first 8 weeks. During the study, participants will undergo assessments including the Myasthenia Gravis - Activities of Daily Living (MG-ADL) score measured at baseline and weeks 22 to 24. Blood samples will be collected to measure antibody levels and total IgG from before the first dose up to week 8 in the sub-study. Safety and efficacy will be closely monitored throughout the trial period.

Researchers are investigating whether a shorter duration of immunotherapy is as effective as the current standard for patients with high-risk malignant skin melanoma who have undergone radical surgery. This phase 3 international study focuses on patients aged 18 and older with stage IIb-c, III, or IV melanoma. The goal is to compare six months versus twelve months of immunotherapy to determine if the shorter treatment can prevent cancer recurrence as well as the longer one, potentially reducing side effects, hospital visits, and healthcare costs. The study treatment involves immunotherapy using drugs nivolumab or pembrolizumab given intravenously according to routine clinical practice. Patients are randomized to receive either six months (experimental group) or twelve months (standard group) of treatment. For those who received neoadjuvant immunotherapy before surgery, treatment durations are adjusted accordingly to total six or twelve months. Follow-up includes imaging scans at baseline, six months, and thirty-six months, along with medical examinations at multiple time points up to three years. If relapse occurs, further evaluations and treatment decisions are made by a multidisciplinary team. Participants will have regular visits for physical exams, imaging tests, and blood work to monitor their health and treatment response. The main outcomes measured are relapse-free survival and distant metastatic-free survival at two years. Overall survival and health economic effects will also be assessed. Patients are followed for up to five years to track survival and any disease recurrence, ensuring close monitoring of safety and effectiveness throughout the study period.

BACKGROUND: The development of robotic-assisted laparoscopic surgery is rapid. It is at least more gentle than open surgery to the patient. During certain types of robotic-surgery i.e. prostatectomies and hysterectomies deep down in the small pelvis the surgeons need to tilt the patient in a steep Trendelenburg (30 degrees head down) position and insufflate CO2 (carbon dioxide) gas into the stomach to reach and visualize the organs properly. According to the law of gravity this entails that the blood inside the vessels is pressed backwards against the pumping heart and afterload increases. To be able to withhold the flow of blood to our vital organs the performance of our heart is challenged. Besides carbon dioxide is blown into the stomach, which even more increases the workload of the heart. There is a substantial risk of acute heart failure during these manoeuvres especially in patients with preexisting heart failure. There are very few studies investigating these problems. Earlier studies have only investigated the effects in healthy ASA (American Society of Anesthesiologists) 1-2 patients. AIM: This study will investigate how patients with known systolic heart failure manage this strain which is included in this new developing type of robotic surgery compared to patients with normal heart function. METHOD: 1. Included patients undergo an echocardiographic investigation before surgery and will be classified in 2 groups: a) Normal systolic function b) Decreased systolic function defined as Ejection Fraction (EF) 45% or lower. 2. After start of anesthesia all patients receive an esophageal doppler and the output values of cardiac stroke volume (SV); cardiac Index (CI), systemic vascular resistance (SVR); pulse pressure variation(PPV), stroke Volume variation (SVV) Peak Velocity (PV)and Flow Time Corrected (FTc) are recorded as well as standard routine parameters during anesthesia. With INVOS (In Vivo Optical Spectroscopy) regional oxygen saturation of the front lobes of the brain is measured. 3. This procedure is repeated after start of Trendelenburg position 30 degrees head down, at the start of pneumoperitoneum and at the return to supine position. 4. The effects of robotic assisted surgery between patients with normal EF compared to patients with EF 45% or lower will be compared. THE IMPORTANCE OF THIS STUDY: The increasing field of robotic-assisted surgery, which often results in shorter and less complicated postoperative care will enable older and more fragile patients to be available for surgery. In contrast these patients encounter new cardiovascular challenges during the anesthesia and extreme positioning surgery. It is therefore most important to be aware of these physiological challenges and how to handle them. This study will also show which patients are not suitable for robotic surgery.

Out-of-hospital cardiac arrest (OHCA) often involves dangerous heart rhythms like ventricular fibrillation (VF) or ventricular tachycardia (VT), which require defibrillation to restore a normal heartbeat. Survival chances decrease the more defibrillations are needed. Recent research suggested that using Double Sequential Defibrillation (DSD), which applies two defibrillators sequentially, may improve survival in patients with refractory VF. This trial aims to evaluate if applying DSD earlier, right after the first failed defibrillation in patients with shockable rhythms, improves 30-day survival compared to standard single defibrillation. Participants will receive either the early DSD strategy, where a second defibrillator is added with electrodes placed on the chest and back (anterior-posterior position) and shocks are delivered sequentially, or the usual care involving standard defibrillation with one defibrillator and pads placed in the anterior-lateral position. The study is an open-label, randomized controlled trial with equal allocation to each group, conducted by emergency medical services equipped with two defibrillators on site. During the trial, emergency teams will screen eligible adult OHCA patients with shockable rhythms who have had at least one unsuccessful defibrillation. The main outcome measured is survival 30 days after the cardiac arrest. The trial involves initial rhythm analysis, delivery of assigned defibrillation methods, and follow-up to assess outcomes. This study could influence future advanced cardiac life support guidelines if early DSD proves beneficial for a wider group of patients.

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.

Researchers are evaluating the effectiveness and safety of a new oral cladribine formulation compared to placebo in adults with Generalized Myasthenia Gravis (gMG). This Phase 3 study also aims to understand the lasting effects, the need for retreatment, and the long-term safety of oral cladribine. Additionally, the study includes an assessment of how the body processes (pharmacokinetics) the new cladribine formulation in participants with gMG. The trial consists of three periods: a double-blind placebo-controlled phase, a blinded extension, and a retreatment phase. Participants will be assigned to one of three groups: placebo, low-dose cladribine, or high-dose cladribine. Each treatment is given in two courses separated by four weeks. The placebo group will receive placebo matching the cladribine schedule. The study's structure allows for evaluation during the initial double-blind period followed by extensions to monitor ongoing effects and retreatment needs. During the study, participants will be assessed using the Myasthenia Gravis - Activities of Daily Living (MG-ADL) scale to measure changes in their condition from baseline to week 24. Researchers will monitor safety and efficacy throughout the study periods. Assessments include clinical evaluations and monitoring for any side effects or adverse events. The total duration includes the initial 24-week double-blind period plus the subsequent extension and retreatment phases to evaluate long-term outcomes.