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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 investigating the drug bezuclastinib in an open-label, two-part Phase 2 study for patients with Advanced Systemic Mastocytosis (AdvSM), including Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL). The study aims to evaluate the safety, effectiveness, and how the drug behaves in the body for these serious conditions. Bezuclastinib is given orally as tablets taken continuously in 28-day cycles. The study has two parts: Part I focuses on identifying safe and tolerable doses of bezuclastinib over 18 months, while Part II evaluates its effectiveness by measuring the objective response rate and confirming the relationship between drug exposure and response during another 18-month period. Participants will undergo assessments including clinical evaluations, laboratory tests, and monitoring of their disease status to determine treatment effects and safety. Researchers will track the drug's impact on the disease and patient health throughout the study, which involves continuous treatment and follow-up over the specified time frames.

Researchers are evaluating the safety and effectiveness of elenestinib (BLU-263) combined with symptom-directed therapy (SDT) compared to placebo plus SDT in people with indolent systemic mastocytosis (ISM) whose symptoms are not well controlled by SDT alone. This Phase 2/3 randomized, double-blind, placebo-controlled study includes participants with ISM and smoldering systemic mastocytosis, and also involves groups for pharmacokinetic studies and participants who previously received a selective KIT inhibitor. The study is divided into multiple parts. Parts 1 and 2 enroll participants with ISM who will receive either elenestinib oral tablets or placebo alongside their symptom-directed therapy. Participants from Part 2 may continue into Part 3, which is an open-label extension where all receive elenestinib. Part K enrolls participants with ISM who have prior experience with selective KIT inhibitors. The study tracks treatment effects and safety over time. Participants will be monitored for up to 5 years, with assessments including the number of treatment-emergent adverse events, changes in symptom scores measured by the ISM-Symptom in Assessment Form, and overall safety monitoring. Evaluations occur at baseline, 13 weeks, 49 weeks, and throughout the long-term follow-up. The study also includes detailed tracking of symptom control and adverse events to evaluate the impact of treatment on participants' health and quality of life.

Researchers are studying acute pyelonephritis (AP), a common bacterial kidney infection in children, focusing on those aged 1 month to less than 3 years without prior urological malformations. The study compares a short 3-day intravenous (IV) antibiotic treatment alone to a 3-day IV treatment followed by 7 days of oral antibiotics. The goal is to see if the shorter IV-only treatment is as effective at preventing infection recurrence and long-term kidney scarring, while possibly reducing antibiotic resistance and preserving gut microbiota diversity. Participants receive either IV ceftriaxone and/or amikacin once daily for 3 days, or the same 3-day IV treatment followed by 7 days of oral cotrimoxazole or cefixime. The study includes procedures like procalcitonin testing and fecal or rectal swabs collected at several points during and after treatment (day 0, 3, 10 or 17, and 31 or 38) to monitor bacterial presence and gut microbiota changes. Treatment begins after initial confirmation of infection and favorable early response. During the study, children are closely monitored for infection recurrence 28 days after completing antibiotics. Assessments include clinical evaluations, urine cultures, and monitoring for any adverse effects. The total participation covers treatment and follow-up periods to ensure safety and measure outcomes such as infection recurrence and bacterial resistance. This is a Phase 4 open-label randomized trial conducted across multiple centers.

Primary mitral regurgitation (MR) is a common heart valve disease that can lead to heart failure and often requires surgery. This condition causes progressive scarring (fibrosis) of the heart muscle due to chronic increased blood volume, which stiffens the left ventricle (LV) and affects its function. Researchers are studying the relationship between LV stiffness measured by 3D ultrasound mechanical wave velocity (MWV) and heart muscle fibrosis measured by cardiac magnetic resonance imaging (CMR) using extracellular volume (ECV) assessment. Participants will undergo ultrasound imaging using a high-frame-rate echocardiography scanner to measure mechanical wave velocity in the heart muscle. In addition, they will have routine exams including 2D/3D echocardiography, CMR imaging, 24-hour electrocardiogram monitoring, blood tests including brain natriuretic peptide levels, and exercise testing with oxygen uptake measurements. These procedures help assess the heart's structure, function, and stiffness. During the study, patients will be evaluated for heart muscle stiffness and fibrosis. Researchers will analyze how well the ultrasound MWV measurements correlate with the CMR fibrosis data. Monitoring includes symptom-limited exercise tests and continuous heart rhythm recording. The study focuses on patients with varying severity of primary MR and aims to improve understanding of heart muscle changes in this condition.

This research aims to evaluate the neurodevelopment at age 6 of children born to women who experienced preterm prelabor rupture of membranes (PPROM) between 22 and 33 weeks of pregnancy. The study compares outcomes after antenatal exposure to nifedipine versus placebo. PPROM complicates 3% of pregnancies and is a leading cause of preterm birth, neonatal death, and maternal infection. While tocolysis with nifedipine may delay delivery to reduce risks of prematurity, it might also increase infection risks and long-term complications like cerebral palsy. Children born to mothers enrolled in the TOCOPROM trial receive follow-up assessments at 6 years old. These include a self-administered parental questionnaire completed online or on paper to evaluate different neurodevelopmental areas. A brief psychological assessment lasting 45 minutes is performed remotely via video conference by a psychologist using the NEMI-3 intelligence test, measuring various cognitive abilities. During the study, parents complete questionnaires and share health book data, especially from the 6-year consultation. The neurodevelopmental outcomes measured include cerebral palsy, developmental coordination disorder, language skills, behavior, and executive functions. The psychological test results are classified into normal, mild delay, or severe delay categories. The study also requires internet and video-conference access for participation in the psychological evaluation.

Researchers are evaluating how well pre-treatment 68Ga-FAPI-46 PET/CT imaging can predict the histological response to neoadjuvant chemo-immunotherapy in patients with early-stage high-risk triple-negative breast cancer (TNBC). This prospective multicenter study focuses on female patients who have not yet been treated and are recommended to receive pembrolizumab combined with chemotherapy as their standard care. The study aims to improve understanding of treatment effectiveness using advanced imaging techniques before therapy begins. Participants will receive neoadjuvant treatment consisting of pembrolizumab 200 mg every three weeks combined first with four cycles of paclitaxel plus carboplatin, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide. After surgery, patients will continue adjuvant pembrolizumab for nine cycles or until cancer recurrence or unacceptable side effects occur. Each participant will undergo a 68Ga-FAPI-46 PET/CT scan before starting treatment, performed on the same machine as the 18F-FDG PET/CT scan and within 14 days prior to therapy. Throughout the study, researchers will monitor participants using scans and tissue analysis to assess histological response to treatment. They will measure the prediction accuracy through the area under the ROC curve at six months. Patient compliance, informed consent, and health insurance coverage are required for participation. Safety and treatment response will be carefully followed during and after the therapy period.

This research aims to evaluate the effects of litifilimab (BIIB059), a monoclonal antibody, in adults with active subacute or chronic cutaneous lupus erythematosus (CLE), with or without systemic lupus erythematosus (SLE). Participants have active skin symptoms of CLE that have not improved with antimalarial therapy or had difficulties continuing that treatment. The study focuses on reducing skin disease activity using several scores including CLA-IGA-R and CLASI, while also assessing safety, immune response, and quality of life. Participants will be randomly assigned to receive either litifilimab or a placebo injection under the skin every four weeks during a 24-week double-blind period where neither participants nor researchers know which treatment is given. After this, all participants will receive litifilimab injections every four weeks for an additional 28 weeks. Those who complete the treatment may join a long-term extension study or enter a follow-up safety period lasting up to 24 weeks. Total participation may last up to 80 weeks. Throughout the study, researchers will monitor skin disease activity using the CLA-IGA-R erythema score and the CLASI-A activity score to see how many participants improve. They will also assess safety, tolerability, immune system effects, and participants' quality of life using questionnaires. These evaluations occur regularly during both treatment periods and follow-up to understand the impact of litifilimab on CLE symptoms and overall health.

Researchers are evaluating the efficacy and safety of Apremilast in patients aged 6 years and older who have Epidermolysis Bullosa Simplex Generalized, a genetic skin condition characterized by fragile skin and blistering. This Phase 2 clinical trial aims to describe how effective Apremilast treatment is in managing this condition over a 20-week period. The study includes three main periods: an initial 8-week treatment period where patients receive Apremilast; a 4-week treatment pause called the dechallenge period; and a second 8-week treatment phase called the rechallenge period. Patients will visit the hospital seven times throughout the study to receive treatment and undergo study procedures. During treatment periods, patients will use the medication as directed and avoid other topical therapies unless approved by the investigator. At each visit, doctors will check patients' vital signs, perform clinical exams, monitor treatment adherence, and record any side effects. Patients will complete questionnaires to provide information about their condition. The main outcome measured is the effectiveness of Apremilast at 20 weeks. This careful monitoring ensures safety while assessing how well the treatment works over the entire study duration.

Researchers are studying adult acute lymphoblastic leukemia (ALL), including three groups: Ph-positive ALL, Ph-negative B-cell precursor ALL, and T-ALL/lymphoblastic lymphoma. The study aims to improve treatment outcomes by incorporating new antibody-based therapies such as blinatumomab and isatuximab and to better define when stem cell transplantation is needed for patients in first remission. This is a prospective, multicenter, randomized clinical trial with three separate patient cohorts. Participants will be assigned to one of three treatment groups based on their ALL subtype. Treatments include blinatumomab with chemotherapy, blinatumomab plus ponatinib with chemotherapy, standard chemotherapy alone, or isatuximab combined with standard chemotherapy. Blinatumomab is given as a continuous infusion for several cycles, ponatinib is taken orally with decreasing doses over time, and isatuximab is administered intravenously for up to 28 infusions. Some patients may also receive allogeneic stem cell transplantation as part of their treatment. During the study, participants will be closely monitored through clinical visits, laboratory tests, and assessments to track survival and disease progression over five years. Researchers will evaluate overall survival and event-free survival as the main outcomes. Patients will also report their experiences and adhere to scheduled treatments and follow-ups to help assess the safety and effectiveness of these new therapies in frontline ALL treatment.