Orleans

Researchers are evaluating the use of early near apneic ventilation compared to usual ultra-protective lung ventilation in patients with severe acute respiratory distress syndrome ARDS who are supported by venovenous extracorporeal membrane oxygenation ECMO. The trial, named CALMDOWN, is a prospective, open-label, multicenter, randomized controlled study aiming to investigate whether early apneic ventilation can help reduce ventilator-induced lung injury, ECMO duration, and mortality by day 60 in this critically ill population. Participants are randomly assigned to one of two groups one group receives near apneic ventilation during the first 3 days of ECMO using BIPAPAPRV or pressure-controlled ventilation with specific settings to maintain airway pressure and minimize ventilation rate. Neuromuscular blockade and sedation may be used as needed. After 3 days, apneic ventilation may continue or switch to ultra-protective lung ventilation at the physicians discretion. The other group receives standard ultra-protective lung ventilation throughout ECMO support with defined ventilator settings. Prone positioning is allowed in both groups based on physician judgment. During the study, participants will be monitored closely for outcomes including mortality at day 60, need for lung transplantation, persistence of ECMO support, and days alive without ECMO from day 0 to day 60. Additional assessments cover mortality and other clinical outcomes up to day 90, duration of ventilation, ICU stay, hospital stay, and complications such as pneumonia, pneumothorax, and right ventricular function. The trial is sponsored by Assistance Publique - Hpitaux de Paris and runs until May 2030.

Researchers are investigating metastatic colorectal cancer mCRC patients who have a specific genetic change called the BRAFV600E mutation. This rare subtype of mCRC often shows poor response to current treatments and has a generally poor outlook. The study aims to collect detailed clinical data and biological samples to better understand this condition, including how patients respond to treatments and what factors predict their survival. It focuses on real-world treatment outcomes and biological markers that might influence therapy choices and resistance. Participants will provide blood samples at multiple times during their treatment, including before and during the first three treatment cycles, at 3 and 6 months after starting each treatment line, and when disease progression occurs following certain therapies. The study gathers up to 390 mL of blood per participant over time to analyze circulating tumor DNA and immune environment factors. This observational approach will help researchers identify biomarkers related to treatment response and disease progression. During the study, participants clinical progress and survival will be tracked for up to five years. Researchers will review overall survival from diagnosis to death and assess how prognostic markers relate to progression-free survival and response to treatments. The study involves collecting tumor tissue samples and blood tests, along with routine follow-up visits. All data collected will contribute to understanding BRAFV600E mCRC and improving future treatment strategies.

This research aims to describe the clinical, histological, and radiological features of rare primary liver cancers. It focuses on collecting tumor and blood samples to better understand these cancers and to evaluate how well treatments used in real-world practice work, with the goal of identifying the best treatment sequences. The study serves as a foundation for future research to find new molecular and imaging biomarkers that could improve diagnosis and prognosis. The study is observational and retrospective, meaning it reviews past cases from multiple centers in France. It collects biological samples and clinical data from patients diagnosed with rare primary liver cancers after January 2018. The study evaluates treatments patients have received in clinical practice without assigning any new treatments or interventions. Participants data, including clinical characteristics, tumor biology, and imaging, will be reviewed for up to five years from diagnosis. Researchers will measure outcomes such as recurrence-free survival for patients without metastases, progression-free survival for those with metastases, and overall survival. The study includes both living patients who consent to participate and deceased patients, aiming to gather comprehensive information to support future translational studies.

Researchers are studying patients with completely removed non-small cell lung cancer NSCLC who have common mutations in the EGFR gene, specifically Del19 or L858R. The study aims to use broad-panel centralized next-generation sequencing NGS testing at the start to better understand molecular factors that predict outcomes and to investigate mechanisms of resistance to the drug osimertinib after treatment. This research focuses on patients with stage pIB to IIIA NSCLC who have undergone thorough preoperative assessments and quality surgical excision reviews. Participants will have plasma circulating tumor DNA ctDNA tested at various stages before surgery optional, 4 to 8 weeks after surgery, before starting adjuvant chemotherapy or osimertinib if given, every 6 months during follow-up, and at relapse if it occurs. Formalin-fixed paraffin-embedded FFPE tissue blocks from surgery and relapse optional will also be collected for molecular analyses. Treatment with osimertinib as adjuvant therapy is planned for up to 3 years, with chemotherapy given beforehand if needed. During the study, patients will be regularly followed every 3 to 6 months with standard care visits and molecular testing. Researchers will monitor the feasibility of the testing approach over 18 months and track the incidence and severity of any side effects related to osimertinib for about 3 years. This ongoing monitoring aims to better understand relapse mechanisms and improve treatment options in metastatic relapse. The total participation duration aligns with the follow-up and safety monitoring periods outlined.

Researchers are evaluating the safety and tolerability of an investigational drug called elritercept, both alone and in combination with the JAK inhibitor ruxolitinib, in adults with myelofibrosis MF. The study also aims to understand how elritercept affects the signs and symptoms of MF, how the body processes the drug, and its effects on anemia when used with or without ruxolitinib. This is a Phase 2 open-label study focusing on participants with anemia related to MF.

Chronic lymphocytic leukemia CLL is the most common type of leukemia affecting blood cells. Researchers are evaluating the safety of combining oral venetoclax with either intravenously infused obinutuzumab or oral acalabrutinib for treating previously untreated CLL. The study focuses on assessing adverse events and changes in disease activity in adult participants. Participants are randomly assigned to one of four treatment groups. Arm A receives oral venetoclax with IV obinutuzumab, including a 5-week venetoclax ramp-up period. Arms B, C, and D receive oral venetoclax combined with oral acalabrutinib, with different venetoclax ramp-up schedules varying between 5 weeks and modified ramp-up periods. The total study duration is approximately 28 months. Participants will attend regular hospital or clinic visits for medical assessments, blood tests, side effect checks, and questionnaires to monitor treatment effects. Researchers will measure the percentage of participants experiencing laboratory tumor lysis syndrome and hyperkalemia during treatment. Safety monitoring and evaluations of tumor burden changes will continue for up to 28 months throughout the study.

Researchers are studying felzartamab in adults with Immunoglobulin A nephropathy IgAN, a kidney disease caused by abnormal IgA antibodies building up in the kidneys leading to inflammation and damage. This Phase 3 clinical trial aims to understand how felzartamab affects proteinuria, the presence of protein in urine, and kidney function in people with IgAN. The safety and how the body processes felzartamab are also being evaluated. Participants will be randomly assigned to receive either felzartamab or a placebo through intravenous infusions during a 24-week treatment period. Some participants with lower kidney filtration rates will be grouped separately but also receive either felzartamab or placebo. After treatment, participants will enter an 80-week follow-up phase. In total, participants will have 17 study visits over about two years. Throughout the study, participants will have urine tests to measure proteinuria, blood tests to assess kidney filtration function, and monitoring for side effects. Researchers will also study felzartamab levels in the blood and check for immune reactions against the drug. Safety will be closely monitored using vital signs, laboratory tests, and physical exams during the entire 104-week period.

Psoriatic arthritis PsA is a type of arthritis that causes joint swelling and stiffness, often occurring in people with the skin condition psoriasis. This study aims to understand how long patients continue treatment and how effective risankizumab RZB is compared to other advanced treatments for PsA in everyday clinical settings. The study will take place outside the United States across about 15 countries, involving between 900 and 1200 adult participants. Participants will receive either risankizumab or other biologic disease-modifying antirheumatic drugs bDMARDs as prescribed by their doctors following local guidelines. Treatments will be given as part of regular medical care without additional interventions from the study. Participants will be followed and observed for 24 months during their routine clinical visits. During the study, participants will attend their usual medical appointments where doctors will monitor their treatment persistence and response. The main outcome measured is how many participants continue their prescribed treatment up to 24 months. There is no expected extra burden or additional procedures for participants beyond their standard care.

Researchers are studying advanced non-small cell lung cancer NSCLC with ALK gene rearrangement treated with next-generation tyrosine kinase inhibitors TKIs as first-line therapy. This prospective study, part of the national EXPLORE ALK cohort, aims to understand the biological characteristics and resistance mechanisms of this cancer type. It involves patients with stage IIIB or IV NSCLC who are not eligible for curative locoregional treatment and have confirmed ALK rearrangement. The study collects tumor tissue samples at diagnosis and at disease progression, if available, to analyze ALK fusion partners, variants, and co-mutations using RNA sequencing. Blood samples are taken at diagnosis, first tumor evaluation, and disease progression to analyze circulating tumor DNA ctDNA with next-generation sequencing. Treatments studied include alectinib, brigatinib, lorlatinib, and entrectinib, either marketed or under early access programs. Participants provide blood samples and allow use of tumor tissue for centralized biological analyses. Researchers measure progression-free survival up to 72 months as the primary outcome, along with overall survival, response rates, duration of response, ctDNA clearance, and resistance mechanisms associated with treatment and ALK fusion partners. The study involves regular evaluations over several years to monitor treatment outcomes and biological changes.

Researchers are evaluating different antimicrobial therapies for infections caused by difficult-to-treat Pseudomonas aeruginosa, a type of bacteria resistant to many common antibiotics. This study focuses on comparing new beta-lactambeta-lactamase inhibitor combinations, cefiderocol, and older treatments like aminoglycosides and colistin to understand their effectiveness in real-life settings for patients facing these challenging infections. The study is a prospective, multicenter cohort involving patients who require intravenous antibiotic treatment for their P. aeruginosa infections. Participating patients will receive one of the available antimicrobial options, and their bacterial samples will be analyzed centrally to assess susceptibility and resistance mechanisms. The study collects clinical data throughout treatment and monitors outcomes such as cure rates, resistance development, adverse events, and mortality. Participants will be followed until hospital discharge and up to 28 days after treatment completion. Researchers will track clinical cures, microbiological eradication, adverse events, emergence of resistance, and acquisition of other multidrug-resistant bacteria. Data collection includes electronic case reports and laboratory testing on bacterial isolates. The total participation duration varies according to hospital stay and follow-up schedules, with rigorous monitoring of safety and treatment outcomes.