Orleans

Researchers are evaluating the effects of early apneic ventilation compared to usual care with ultra-protective lung ventilation in patients with severe acute respiratory distress syndrome (ARDS) who require venovenous extracorporeal membrane oxygenation (ECMO). This Phase 3, open-label, multicenter trial aims to examine whether early apneic ventilation can reduce lung injury, shorten ECMO duration, and lower mortality at 60 days in this critically ill population. Participants are randomized to receive either ECMO plus near apneic ventilation or ECMO plus ultra-protective lung ventilation. Near apneic ventilation is applied during the first three days of ECMO using BIPAP/APRV or pressure-controlled ventilation, with specific settings to maintain airway pressures and low respiratory rates. After three days, apneic ventilation may continue or standard ultra-protective ventilation is used. The ultra-protective lung ventilation group receives low tidal volume and pressure ventilation settings until ECMO weaning. Prone positioning during ECMO is allowed at the physician's discretion in both groups. Throughout the study, researchers monitor mortality, need for lung transplantation, ongoing ECMO support, and days alive without ECMO up to day 60. Participants undergo clinical assessments and ventilator management according to the assigned strategy. Consent procedures accommodate emergency inclusion with surrogate consent when needed, and follow-up includes evaluation of lung recovery and survival outcomes over the 60-day period.

Researchers are studying patients with metastatic colorectal cancer (mCRC) who have a specific BRAFV600E mutation. This rare subtype of mCRC has poor prognosis and resistance to current treatments, especially in tumors with microsatellite stability or proficient mismatch repair. The study aims to collect detailed clinical data and biological samples to better understand treatment outcomes, resistance, and survival in real-world settings. Participants will provide blood samples and tumor tissue samples to support various research goals. The study will evaluate circulating tumor DNA during different lines of metastatic treatment to predict treatment response and resistance. It will also analyze the immune environment of BRAFV600E mCRC tumors and study specific subgroups with mismatch repair deficiencies. Clinical management data will be collected to inform future therapeutic approaches. During the study, patients will be monitored regularly with blood sample collections of 30 mL at each time point. Researchers will gather information about treatments, survival, and biological markers over time. The main outcome measured is overall survival from diagnosis up to five years. Patients must be able to comply with study procedures and provide informed consent. The study aims to improve knowledge of this aggressive cancer subtype and support development of new treatments.

Researchers are conducting a French multicenter retrospective study to describe the clinical, histological, and radiological features of rare primary liver cancers. The study aims to collect biological tumor and blood samples and evaluate the effectiveness of treatments used in clinical practice to determine the best therapeutic sequences. This research will serve as the foundation for future translational studies to identify new molecular, histological, circulating, and radiological tumor biomarkers useful for diagnosis, prognosis, and treatment guidance. This study involves collecting data from patients diagnosed with rare liver cancers such as hepatocholangiocarcinoma, fibrolamellar hepatocellular carcinoma, epithelioid hemangioendothelioma, and hepatic angiosarcoma since January 1, 2018. Both living patients who agree to participate and deceased patients are included. Biological samples and tumor blocks are collected for analysis. Treatments received by patients in routine practice are reviewed to assess their efficacy and help define optimal treatment sequences. Participants provide consent for biological studies if living, and their medical records and tumor characteristics are reviewed. Researchers will describe the clinical, histological, and radiological tumor features and monitor outcomes up to five years from diagnosis. This detailed data collection supports long-term evaluation of rare liver cancers and aids in developing future biomarkers and therapeutic strategies.

Researchers are studying patients with completely removed non-small cell lung cancer (NSCLC) who have common EGFR mutations (L858R and Del19). The study aims to include broad-panel centralized genetic testing at the start to better understand factors predicting outcomes and resistance to the drug osimertinib when used after surgery. It also investigates the molecular changes linked to cancer returning during or after osimertinib treatment to find better treatment options if the cancer comes back in a metastatic form. The study involves collecting plasma circulating tumor DNA (ctDNA) samples before surgery (optional), 4 to 8 weeks after surgery, before starting any adjuvant chemotherapy or osimertinib treatment, every six months during follow-up, and at relapse. Tumor tissue samples from surgery and optionally at relapse are also collected for molecular analysis. Patients may receive adjuvant chemotherapy if needed before starting osimertinib, which is given with the intent to treat for three years. Participants will be regularly followed every 3 to 6 months according to standard recommendations. Researchers will monitor genetic markers using blood and tissue samples to study cancer relapse and resistance. The main outcome is to assess the feasibility of this molecular monitoring approach over an 18-month period. Safety and long-term follow-up are included, aiming to improve treatment decisions for patients with resected NSCLC and EGFR mutations.

Researchers are evaluating the safety, tolerance, and effects of elritercept, alone and combined with the JAK inhibitor ruxolitinib, in adults with myelofibrosis (MF). This Phase 2 study aims to learn how elritercept impacts the signs and symptoms of MF, how the body processes the drug, and its effects on anemia and blood cell counts. Elritercept is an investigational protein designed to boost red blood cell and platelet production by blocking certain signals that suppress blood formation. Participants receive elritercept as a subcutaneous injection either alone or in combination with oral ruxolitinib tablets. The study includes different groups based on prior treatments: those previously treated with JAK inhibitors and those currently on ruxolitinib with insufficient disease control or side effects limiting dose. A specific group in Brazil includes participants with no prior JAK inhibitor treatment. The study monitors participants over about 8 years, including long-term extension periods. During the study, participants will be regularly assessed for side effects, blood cell levels, and overall health. Researchers will track adverse events and serious side effects from informed consent through 30 days after the last dose. Other evaluations include laboratory tests, symptom assessments, and pharmacokinetic analyses to understand how elritercept behaves in the body. Participants agree to follow all study procedures and return for follow-up visits throughout the study period.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia affecting blood cells. This research aims to evaluate the safety of the drug venetoclax when combined with either obinutuzumab or acalabrutinib for treating adults with previously untreated CLL. The study focuses on monitoring side effects and changes in disease activity to better understand treatment risks, including the risk of tumor lysis syndrome (TLS). Participants will be assigned to one of four treatment groups. All will receive oral venetoclax with different ramp-up schedules combined with either intravenous obinutuzumab or oral acalabrutinib. Treatment arms vary in their dosing schedules and combination therapies. The total study period lasts about 28 months, during which participants receive their assigned treatments and monitoring. Throughout the study, participants will have regular visits at hospitals or clinics for medical exams, blood tests, and side effect checks. Questionnaires will also be completed to assess their condition. Researchers will track the occurrence of TLS and other laboratory indicators related to safety. This ongoing monitoring will help understand treatment effects and ensure participant safety over the study duration.

Researchers are evaluating the effects of felzartamab in adults with Immunoglobulin A nephropathy (IgAN), a kidney disease caused by the buildup of abnormal IgA antibodies in the kidneys. This buildup leads to inflammation and damage, causing protein to appear in the urine. The study aims to understand how felzartamab influences proteinuria and kidney function, while also assessing the safety and how the body processes this treatment. This is a Phase 3, randomized, double-blind, placebo-controlled study focusing on adults with IgAN. Participants will be randomly assigned to receive either felzartamab or a placebo through intravenous (IV) infusions. Neither the participants nor the researchers will know which treatment is given. The treatment period lasts 24 weeks followed by an 80-week follow-up period. In total, participants will attend 17 study visits over about 2 years to receive infusions and participate in study activities. During the study, participants will undergo assessments including urine tests to measure protein levels, kidney function evaluations, and safety monitoring. Researchers will track changes in proteinuria from the start of the study to Week 36 as the main outcome. Additional measurements will include kidney function, clinical endpoints, and the study of how felzartamab is processed by the body. Participant safety and long-term effects will be monitored throughout the study and follow-up periods.

Psoriatic arthritis (PsA) is a type of arthritis that causes joint swelling and stiffness and is often seen in people with the skin condition psoriasis. It results from an overactive immune system attacking healthy tissue. This research aims to describe the long-term use and effectiveness of risankizumab (RZB) compared to other advanced treatments for managing PsA in everyday clinical care. The study is not conducted in the United States but will take place in about 15 countries and include between 900 and 1200 adult participants. Participants will be assigned in a 2 to 1 ratio to receive either risankizumab or other advanced therapeutic agents. The treatments will be given following usual medical guidelines, including approved dosing and indications, as determined by local regulations and professional standards. All study visits will occur during routine clinical care with no extra burden on participants. Participants will be followed and monitored for 24 months to observe treatment persistence. During the study, participants will continue their regular clinical visits without additional procedures or tests required by the study. Researchers will measure how many participants continue their prescribed treatment over the 24-month period. The study focuses on real-world treatment patterns and outcomes in patients with active PsA who have previously shown an inadequate response or intolerance to certain medications. Safety monitoring will align with routine clinical practice throughout the study duration.

Researchers are studying the biological features of advanced ALK-rearranged non-small cell lung cancer (NSCLC) in patients treated with new generation tyrosine kinase inhibitors (TKIs) as their first therapy. This study is part of the national EXPLORE ALK cohort, a multi-center observational project in France, focusing on patients with this specific genetic alteration. The goal is to better understand the tumor biology and resistance mechanisms by analyzing samples from diagnosis through disease progression. The study collects tumor tissue samples at diagnosis and, when possible, at disease progression for RNA sequencing to identify ALK fusion partners, variants, and co-mutations. Blood samples are also taken at diagnosis, first tumor evaluation, and at progression to analyze circulating tumor DNA (ctDNA) using next-generation sequencing panels that detect mutations, fusions, and other genetic changes. These biological analyses are centralized at specialized centers such as the Léon Bérard Center and Rouen University Hospital. Patients are treated with approved ALK inhibitors like alectinib, brigatinib, lorlatinib, or entrectinib as part of their standard care. Participants will provide blood samples at multiple time points and, if possible, tumor biopsy samples for detailed genetic analysis. Researchers will monitor the progression-free survival from treatment start for up to 72 months. The study involves regular evaluations to assess tumor status and collect biological material to track genetic changes over time. Consent for sample collection and participation in the study is required, and patient data is managed within the national health system framework.

Researchers are evaluating the effectiveness of different antimicrobial treatments for infections caused by difficult-to-treat Pseudomonas aeruginosa bacteria. This infection is especially challenging for patients who are critically ill or have weakened immune systems. The study focuses on comparing new beta-lactam/beta-lactamase inhibitor combinations, cefiderocol, and older drugs like aminoglycosides and colistin in real-life clinical settings across multiple hospital centers in France. Participants will receive intravenous antimicrobial therapy tailored to treat their difficult-to-treat P. aeruginosa infection. The study observes the use of new and older antimicrobial drugs to assess their clinical efficacy. Patient data and bacterial samples will be collected and analyzed centrally to better understand drug resistance mechanisms and treatment outcomes. Participants will be monitored for clinical cure shortly after completing therapy and on Day 7 ± 2 days. Researchers will collect clinical information through electronic case-report forms and send bacterial isolates to a national center for detailed testing. Outcomes include cure rates, resistance development, adverse events, and mortality rates, with follow-up during hospitalization and up to 28 days after treatment. The study aims to provide valuable real-world data on treating these challenging infections.