Coppito

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 investigating whether treating severe crowding of the upper front teeth early, during the mixed dentition stage, is more effective than waiting until the permanent teeth have erupted in children aged 6 to 9 years with at least 6 millimeters of crowding. This trial also aims to compare differences in oral health related quality of life, spontaneous adaptation of the lower dental arch after upper jaw expansion, and cost-effectiveness between early treatment and treatment in the permanent dentition. Children in the experimental group receive treatment with a maxillary expansion device designed to widen the upper jaw. This device is attached to the second deciduous molars and deciduous canines, and parents activate it daily or every other day to create enough space for the lateral incisors to erupt. The expansion may be paused for several months if needed to allow spontaneous correction of the permanent molars before continuing. The device is retained until the lateral incisors fully erupt. Control group participants receive standard care without early expansion. Participants and their parents complete questionnaires on pain, discomfort, and oral health related quality of life during and after treatment. Researchers use low-dose CT scans and digital model measurements to assess crowding, tooth alignment, arch dimensions, and palatal volume at the start and after a five-year follow-up. A cost-effectiveness analysis compares early expansion treatment with treatment in the permanent dentition. The total observation period lasts about five years to evaluate long-term spontaneous alignment of the upper front teeth.

Researchers are evaluating treatment options for patients with metastatic colorectal cancer (mCRC) who have a specific genetic profile: RAS/BRAF wild type in tumor tissue but RAS mutations detected in liquid biopsy. This phase III randomized study aims to determine whether first-line treatment with bevacizumab (an anti-VEGF antibody) plus chemotherapy (FOLFIRI) improves progression-free survival (PFS) compared to the standard treatment with cetuximab (an anti-EGFR antibody) plus FOLFIRI. The study also investigates if switching treatment to bevacizumab plus FOLFIRI upon detection of RAS mutations in liquid biopsy during cetuximab treatment, without clinical or radiological disease progression, affects PFS. Participants with RAS mutations detected at the first liquid biopsy are randomly assigned in a 1:1 ratio to receive either FOLFIRI plus cetuximab or FOLFIRI plus bevacizumab. Those with RAS wild type at first biopsy receive FOLFIRI plus cetuximab for up to 8 cycles outside the study protocol. After 4 months, a second liquid biopsy is performed, and if RAS mutations appear without disease progression, patients are again randomized to continue cetuximab or switch to bevacizumab. Treatment continues until disease progresses, unacceptable side effects occur, consent is withdrawn, or safety concerns arise. Throughout the study, plasma samples are analyzed for KRAS, NRAS, and BRAF V600 mutations using the Idylla system, and later by next generation sequencing to explore tumor heterogeneity and its relation to patient outcomes. Researchers will monitor progression-free survival for up to 36 months from randomization. This study seeks to identify the most effective monoclonal antibody therapy for this patient group and assess the clinical utility of liquid biopsy combined with tissue analysis for detecting mutations.