San Donato Milanese

Researchers are evaluating a predictive algorithm called the Multifactorial Dynamic Perfusion Index (MDPI) that estimates the risk of acute kidney injury after cardiac surgery involving cardiopulmonary bypass (CPB). This multicenter observational prospective trial is divided into three parts: validating the MDPI in 800 adult patients across two institutions, developing a new MDPI version for infants under 20 kg undergoing cardiac surgery, and exploring whether the MDPI can predict other postoperative complications and mortality within 30 days. The MDPI uses seven variables collected dynamically during CPB, including hematocrit, oxygen delivery, mean arterial pressure, CPB duration, lactate levels, and transfusions. Since many of these factors can be adjusted by the perfusionist or anesthesiologist, the MDPI may serve as an on-line monitoring tool to guide treatment during surgery. The study collects data during cardiopulmonary bypass using standard CPB monitors and manual inputs of blood lactates and transfusions. Work Package 1 focuses on adults and involves collecting data from 800 patients to externally validate the MDPI and check its ability to predict acute kidney injury based on the K-DIGO classification. Work Package 2 develops a specialized MDPI for infants under 20 kg undergoing cardiac surgery, gathering additional infant-specific variables. Work Package 3 examines whether the MDPI predicts other complications like prolonged ventilation, intensive care stay, bleeding, transfusions, and 30-day mortality, and aims to integrate the MDPI into dedicated monitoring devices. Participants undergo cardiac surgery with CPB, during which the seven key parameters are recorded using monitors. Postoperative monitoring includes measuring creatinine for 48 hours to identify acute kidney injury and collecting data on other complications and outcomes. Researchers will assess the MDPI's accuracy for predicting these events using statistical methods. The study requires informed consent and excludes emergency surgeries and patients on dialysis. Overall, patient involvement includes CPB parameter collection, follow-up kidney function tests, and monitoring for postoperative complications and mortality within 30 days after surgery.

Researchers are evaluating the safety and effectiveness of three different doses of MORF-057 in adults with moderately to severely active Crohn's disease (CD). This Phase 2 study is randomized, double-blind, placebo-controlled, and conducted at multiple centers. It aims to compare MORF-057 to placebo to see how well it works in reducing disease activity and symptoms in this patient population. Participants will first go through a 14-week induction period where they receive one of three doses of MORF-057 or a matching placebo, all given orally. After this, all participants will enter a 38-week maintenance phase where they receive open-label MORF-057. Those who complete these 52 weeks of treatment may continue in a 52-week long-term extension to further monitor treatment effects and safety. Throughout the study, participants will have evaluations to assess their response to treatment using endoscopic scoring at Week 14. Researchers will monitor safety, symptom changes, and disease activity over the full treatment and extension periods. Study visits will include assessments, questionnaires, and clinical monitoring to track participants' health and treatment adherence over time.

Researchers are evaluating the safety and effectiveness of NNC0487-0111 for people with excess body weight and knee osteoarthritis. This Phase 3 study compares NNC0487-0111 to a placebo, a treatment with no active medicine, to see if it helps reduce weight and knee pain. Participants have knee osteoarthritis diagnosed by specific clinical and radiographic criteria and experience ongoing knee pain. Participants receive weekly injections under the skin using a pre-filled pen injector. The injections, either NNC0487-0111 or placebo, are given in the thigh, abdomen, or upper arm. The study treatments include two dose levels of NNC0487-0111. Treatment assignment is randomized and blinded, meaning participants receive either the medicine or placebo by chance, not by choice. During the study, participants will be monitored for changes in body weight and knee pain using a standardized pain questionnaire over about 80 weeks. They will follow specific instructions about pain medication before assessments. Researchers will track treatment effects, safety, and any side effects throughout the study period.

Researchers are evaluating the effect of ziltivekimab on reducing atherosclerotic plaque in the blood vessels of the heart in people who have had a heart attack. This phase 3 study aims to determine if ziltivekimab can reduce plaque compared to a placebo. Ziltivekimab is a new medicine not yet approved anywhere in the world, and the study will last about 15 months. Participants will be randomly assigned to receive either ziltivekimab or a placebo, both given by injection under the skin. The study includes imaging of the coronary arteries using intravascular ultrasound and other techniques to measure changes in plaque over 52 weeks. Treatment starts as soon as possible, within 48 hours after a heart procedure called percutaneous coronary intervention (PCI). During the study, participants will undergo imaging tests to assess plaque changes in the heart vessels, blood tests, and safety monitoring. The main outcome measured is the change in percent atheroma volume in the arteries from the start of treatment to 52 weeks. Participants will be followed for about one year to track the effects and safety of the treatment.

Researchers are evaluating the safety and effectiveness of two drugs, eltrekibart and mirikizumab, in adults with moderately to severely active ulcerative colitis (UC). This study is a phase 2 trial lasting about 4 to 5 years, aiming to understand how well these treatments work alone or together for this chronic condition. Participants will receive either eltrekibart alone, mirikizumab alone, a combination of both, or a placebo. The treatments are administered as drugs, and the study includes a screening period of up to 35 days before enrollment. The total participation time for each person is approximately 69 weeks, which includes the screening and treatment periods. During the trial, participants will be closely monitored to assess the percentage who achieve clinical remission by week 12. Researchers will conduct regular evaluations, which may include medical assessments and questionnaires, to track the safety and effects of the treatments. The study emphasizes careful follow-up to ensure participant safety and to gather detailed information about the therapies over the entire study duration.

Researchers are studying the safety and effectiveness of long-acting antibodies given alone or in combinations to adults with moderately to severely active ulcerative colitis (UC). This Phase 2, multicenter platform trial aims to find treatments that can improve symptoms and induce remission in people diagnosed with UC for at least 3 months. The study includes participants with active disease confirmed by endoscopy and histology and with moderate to severe symptoms based on a scoring system. The trial has two parts. Part A is an open-label phase testing three different monotherapy drugs to assess safety and initial effectiveness. Part B will be a randomized, placebo-controlled phase where participants receive one of six interventions (three monotherapies or three combinations) or placebo to compare outcomes. Treatments involve intravenous (IV) induction followed by subcutaneous (SC) maintenance dosing. Different treatment arms may start and finish at varying times during the study. Participants will undergo endoscopy and histology to confirm disease activity at screening, with regular monitoring throughout the study. Researchers will evaluate changes in disease severity using the Robarts Histopathology Index and measure the percentage of participants achieving clinical remission by Week 12. Safety and efficacy will be closely followed during and after treatment. The total study duration depends on treatment arm timelines and follow-up requirements.

Researchers are conducting a Phase 3 multicenter, randomized, double-blind, placebo-controlled trial to assess the safety and effectiveness of navenibart in preventing attacks in adults and adolescents with type 1 or type 2 hereditary angioedema (HAE). This study compares navenibart to a placebo to determine its ability to reduce the frequency of HAE attacks. Participants will receive either navenibart or a placebo as subcutaneous injections. The study treatment period lasts for 6 months, during which the number of investigator-confirmed HAE attacks will be tracked and analyzed to evaluate the treatment's impact. During the trial, participants will be closely monitored for HAE attack frequency and safety. Researchers will collect data on the number of attacks from Day 1 through Day 181 to measure treatment efficacy. Safety assessments will also be conducted throughout the study to ensure participant well-being.

Researchers are evaluating the effects of the drug orforglipron compared with a placebo on cardiovascular outcomes in adults who have atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). This is a Phase 3, randomized, double-blind, placebo-controlled study designed to investigate major adverse cardiovascular events over a long period. Participants will receive either orforglipron or a placebo orally. The study is event-driven and will continue until the occurrence of major cardiovascular events or up to about 5 years. The treatments are administered without revealing to participants which group they are in to ensure unbiased results. During the study, participants will be monitored for the time to the first occurrence of a major cardiovascular event. Researchers will collect data from baseline through the end of the study, which lasts approximately 5 years. Regular assessments will help evaluate the safety and effects of the treatments on cardiovascular health in this population.

Researchers are evaluating the workflow of a pulsed field (PF) ablation system using the VARIPULSE catheter and TRUPULSE generator with new VARIPULSE Pro software in people with two types of irregular heartbeat: paroxysmal atrial fibrillation (PAF), where episodes start and stop on their own, and persistent atrial fibrillation (PsAF), which lasts over 7 days and does not stop on its own. The study focuses on how this system works in treating these heart rhythm disorders. The study uses the pulsed field ablation system, which includes the VARIPULSE catheter and TRUPULSE generator with VARIPULSE Pro software, to perform cardiac ablation. This procedure aims to isolate pulmonary veins or treat atrial flutter. The exact treatment details, such as dosing or schedules, are not described, but the intervention involves applying pulsed fields to the heart tissue. Participants will undergo the ablation procedure while various measurements are taken during the operation, including total procedure time, pulsed field application time, number of applications per pulmonary vein and other heart locations, pulmonary vein isolation time, fluoroscopy time, catheter dwell time, and acute effectiveness. Monitoring and follow-up requirements are not detailed, but participants must comply with all testing and follow-up as part of the study.

Researchers are evaluating the efficacy and safety of induction therapy with Afimkibart (also called RO7790121) in people aged 16 to 80 years who have moderately to severely active Crohn's disease. This Phase III, multicenter, double-blind, placebo-controlled study focuses on how well Afimkibart works compared to placebo in improving symptoms and healing the intestine. Participants will receive Afimkibart either as an intravenous (IV) infusion or a subcutaneous (SC) injection. The study includes a placebo group receiving a matching IV infusion. Treatment is given during the induction phase to assess the initial response. During the study, participants will be monitored for clinical remission using the Crohn's Disease Activity Index and for endoscopic response at 12 weeks. Researchers will assess safety, effectiveness, and any side effects throughout the study. Participants will undergo evaluations including symptom tracking and medical tests to measure treatment outcomes.