Paris

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.

This multicenter interventional study evaluates the progression of coronary artery disease over 5 years in adults aged 30 to 60 years with genetically confirmed heterozygous familial hypercholesterolemia HeFH. The study addresses challenges in cardiovascular risk assessment for HeFH patients, focusing on both calcified and non-calcified plaques using advanced imaging techniques. It aims to better understand plaque burden changes and classify coronary stenosis using the CAD-RADS v2.0 system, comparing baseline data from 2018-2022 with current findings. Participants undergo coronary computed tomography angiography CCTA with iodinated contrast to visualize coronary arteries. The study includes 300 patients divided into protected and non-protected groups based on their clinical characteristics. Individual participation lasts from one day up to one week, with the overall study period spanning 2 years. Extended follow-up for up to 10 years will use routinely collected medical data to monitor cardiovascular events and disease progression. During the study visit, participants receive detailed imaging assessments, clinical exams, and questionnaires measuring health status and cardiovascular risk factors. Researchers measure coronary plaque volume, lesion types, calcium scores, arterial dimensions, and other biomarkers. They also evaluate quality of life and symptoms using validated surveys. Safety and cardiovascular events are tracked through long-term medical record review. This comprehensive evaluation helps identify changes in coronary artery disease and related health outcomes over time.

This research aims to improve early diagnosis and classification of rheumatic diseases, which affect bones and joints. Rheumatic diseases are typically diagnosed using clinical signs, biological tests, and imaging, but in about 20% of cases, the diagnosis remains unclear, delaying treatment. Conventional methods may lack sensitivity and specificity for early detection, so the study explores novel biomarkers from biological samples to assist diagnosis and patient classification. The study collects biological samples such as synovial fluid via joint aspiration, blood through venous puncture, and tissue samples during surgery, which are part of routine patient care. These samples will be analyzed using both conventional laboratory tests like histology, immunodetection, and PCR, as well as innovative techniques such as Raman spectroscopy and nanospectroscopy. The investigators aim to detect new biomarkers that can better characterize rheumatic diseases and their progression. Participants provide samples during their routine care procedures, and researchers analyze the chemical, biological, and protein changes in these samples using advanced laboratory methods. The primary outcomes include spectral analysis of tissues and biofluids with surface-enhanced Raman spectroscopy, and protein and RNA expression using immunodetection and PCR techniques. This observational study involves ongoing data collection until 2029, with no direct intervention beyond sample collection during standard medical procedures.

Researchers are investigating CGT9486, also known as bezuclastinib, in an open-label Phase 2 study for patients with Advanced Systemic Mastocytosis AdvSM. This includes those diagnosed with 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, pharmacokinetics, and pharmacodynamics of bezuclastinib in this patient population. Participants will receive bezuclastinib tablets orally, taken continuously in 28-day cycles. The study is divided into two parts Part I focuses on identifying effective and tolerable dosing exposures over 18 months, while Part II evaluates the drugs efficacy by measuring objective response rates and confirming the exposure-response relationship, also over 18 months. Additional assessments include effects on mutation allele burden, serum tryptase levels, histopathologic changes, spleen and liver volume, and safety monitoring. During the study, participants will undergo various clinical evaluations, including laboratory tests, imaging to monitor organ size changes, and assessments of disease response and progression. Researchers will track adverse events and pharmacokinetic profiles throughout the 18 months. The study involves continuous monitoring of participants to understand the treatments impact on survival and disease progression over this period.

Researchers are evaluating the safety and effectiveness of elenestinib BLU-263 combined with symptom directed therapy SDT compared to placebo plus SDT in adults with indolent systemic mastocytosis ISM whose symptoms are not well controlled by SDT alone. This randomized, double-blind, placebo-controlled Phase 23 study includes multiple parts to assess different doses and durations of elenestinib treatment, including an open-label extension for participants finishing earlier phases. The study also enrolls participants who have previously received an approved selective KIT inhibitor and includes pharmacokinetic groups. Participants receive oral elenestinib or placebo once daily alongside SDT, which is personalized based on individual symptom management needs. Part 1 focuses on short-term treatment lasting up to 12 weeks, while Part 2 extends treatment to approximately 48 weeks. Part 3 and other parts allow treatment for up to about 5 years. The study monitors participants through these phases to evaluate how elenestinib affects symptoms, disease markers, and safety over time. During the study, participants undergo regular assessments of symptoms using the ISM-Symptom Assessment Form ISM-SAF, laboratory tests including serum tryptase and KIT D816V allele levels, bone marrow evaluations, and quality of life measures. Researchers track adverse events and changes in disease-related factors at various points up to 5 years. This thorough monitoring helps measure treatment effects and safety over both short and long-term periods, with total participation lasting several years depending on the study part.

This research aims to evaluate antibiotic treatments for acute pyelonephritis AP in children aged 1 month to 3 years. It compares a shorter intravenous IV antibiotic course of 3 days alone to a longer treatment consisting of 3 days IV followed by 7 days of oral antibiotics. The goal is to see if the shorter IV treatment is as effective in curing AP and preventing recurrence and renal scarring, while reducing the risk of antibiotic resistance and preserving gut microbiota diversity. Participants are randomly assigned to one of two groups. The experimental group receives only 3 days of IV antibiotics with ceftriaxone andor amikacin, after which treatment is stopped. The control group receives the usual care of 3 days IV antibiotics followed by 7 days of oral antibiotics, either cotrimoxazole or cefixime. The study includes collection of fecal or rectal swabs and blood tests to assess microbiota and resistance. Treatment effectiveness and safety are compared between groups. During the study, children are monitored for fever, symptoms, and urine cultures to confirm infection clearance. Researchers measure recurrence of febrile urinary tract infections within 28 days after treatment ends and follow clinical cure at 10 or 17 days depending on the group. Additional assessments include monitoring recurrence at 90 days, antimicrobial resistance in gut bacteria, and intestinal microbiota diversity over about a month. Participation lasts through treatment and follow-up visits up to several weeks.

Researchers are investigating the relationship between left ventricular LV myocardial stiffness and myocardial interstitial fibrosis in people with primary mitral regurgitation MR, a common heart valve disease that can lead to heart failure. The study aims to evaluate how 3D ultrasound measurements of mechanical wave velocity MWV in the heart muscle relate to fibrosis measured by cardiac magnetic resonance imaging CMR. Participants will undergo routine tests including 2D and 3D echocardiography with MWV imaging, CMR scans, 24-hour electrocardiogram monitoring, blood tests including brain natriuretic peptide levels, and symptom-limited exercise echocardiography with oxygen uptake measurements. This observational study involves no treatment but collects detailed imaging and clinical data to better understand myocardial stiffness and fibrosis. During the study, patients will have comprehensive heart imaging and monitoring to assess heart function and stiffness. Researchers will measure correlations between LV stiffness and myocardial fibrosis, as well as links to clinical stages of MR, LV mass, and heart strain. The primary outcome is the correlation between LV stiffness assessed by 3D MWV and fibrosis measured by CMR extracellular volume. The study starts in October 2024 and continues through November 2027.

Researchers are evaluating the neurodevelopmental outcomes at age 6 of children born to women who experienced preterm prelabor rupture of membranes PPROM between 22 and 33 weeks of pregnancy. This study compares antenatal exposure to nifedipine versus placebo to understand potential effects on child development after early membrane rupture, a condition linked to preterm birth and associated risks for both mother and child. The trial includes two groups one exposed to oral nifedipine with a loading dose followed by maintenance doses over 48 hours, and the other exposed to a matching oral placebo. The original TOCOPROM trial assessed short-term tocolysis effects, and this follow-up, called TOCOKIDS, aims to assess longer-term developmental effects at school age. Participants will complete a self-administered parental questionnaire online or on paper, and children will undergo a brief remote psychological assessment by video conference. Researchers will collect health data from medical records and assess multiple developmental domains including cerebral palsy, coordination, language, behavior, and executive functions. The study monitors neurodevelopmental and health outcomes up to 6 months after inclusion, with a total follow-up period reaching 6 years of age.

Researchers are evaluating how well a special imaging scan called 68Ga-FAPI-46 PETCT can predict the response of early-stage high-risk triple-negative breast cancer TNBC to treatment before starting therapy. This study focuses on patients receiving a combination of pembrolizumab, a type of immunotherapy, with chemotherapy as a standard care approach. The study is prospective and involves multiple centers collaborating to understand treatment outcomes better. Patients will receive pembrolizumab at a dose of 200 mg every three weeks alongside 4 cycles of paclitaxel plus carboplatin chemotherapy, followed by 4 cycles of either doxorubicin or epirubicin plus cyclophosphamide. After surgery to remove the tumor, participants will continue with up to 9 cycles of pembrolizumab as adjuvant therapy or until cancer returns or unacceptable side effects occur. Before treatment begins, each patient will have a 68Ga-FAPI-46 PETCT scan performed within 14 days, using the same machine as the standard 18F-FDG PETCT scan. During the study, researchers will collect imaging data and monitor patients throughout the entire treatment and follow-up period. They will assess how well the imaging scan predicts the tumors histological response to therapy by measuring outcomes such as the area under the ROC curve at 6 months. The study will also compare the predictive and prognostic performance of the 68Ga-FAPI-46 PETCT scan against the standard 18F-FDG PETCT scan. Participants will be followed closely for safety and treatment response during the neoadjuvant, surgical, and adjuvant phases of care, with the study ending by November 2032.

Researchers are evaluating the efficacy and safety of Apremilast in patients aged 6 years and older with Epidermolysis Bullosa Simplex generalized, a genetic skin condition. This phase 2 open-label study aims to describe how well Apremilast works in reducing symptoms, particularly the occurrence of new blisters, over a 20-week period. Participants will undergo three distinct periods an initial 8-week treatment phase called challenge, followed by a 4-week period without treatment called dechallenge, and a second 8-week treatment phase called rechallenge. During these periods, patients will take Apremilast and have regular visits to the hospital where doctors will perform study procedures and monitor progress. Throughout the study, participants will have seven visits where doctors will check vital signs, perform clinical examinations, review treatment adherence, and monitor for any side effects. Patients will also complete various questionnaires about their condition. The main measure of success is the efficacy of Apremilast at 20 weeks, along with safety assessments. The total study duration for each participant is 20 weeks.