Cholet

Researchers are evaluating the effectiveness of camizestrant compared to standard endocrine therapy in patients with early breast cancer that is estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-). These patients have an intermediate or high risk of cancer recurrence and have already completed local treatments such as surgery and possibly chemotherapy, alongside at least 2 years and up to 5 years of standard adjuvant endocrine therapy. The study is a Phase III, open-label trial designed to assess outcomes over a long term. Participants will be randomly assigned to receive either camizestrant, an oral selective estrogen receptor degrader, or one of several standard endocrine therapies including tamoxifen, anastrozole, letrozole, or exemestane, administered according to local approved guidelines. The treatment duration for both groups is planned to last 60 months. Eligible patients may have previously used CDK4/6 inhibitors, and the study will specifically include those with intermediate or high risk of recurrence as determined by clinical and biological markers. During the study, participants will be monitored for up to 10 years from the last patient's randomization to evaluate invasive breast cancer-free survival. Additional outcomes include invasive disease-free survival, distant relapse-free survival, overall survival, safety, and clinical outcome assessments. The study involves ongoing assessments of health status, treatment effects, and safety to determine the long-term benefits and risks of camizestrant compared to standard therapies.

Researchers are evaluating the safety and effectiveness of brenipatide at different doses compared with a placebo in adults with uncontrolled moderate to severe asthma. This Phase 2 study focuses on participants who have a history of asthma requiring controller medication and recent severe asthma exacerbations. The goal is to better understand how brenipatide impacts asthma control over an extended period. Participants will receive either brenipatide or a placebo, both administered by subcutaneous injection. The study includes a 52-week treatment period during which the effects of the drug on asthma exacerbations and symptoms will be monitored. This randomized, double-blind approach helps compare the responses between the treatment and placebo groups. Study involvement lasts about 65 weeks, covering screening, treatment, and follow-up phases. During the study, researchers will assess participants' asthma control using questionnaires and track the annual rate of asthma exacerbations. Safety and treatment responses will be closely monitored throughout the trial to evaluate the drug's impact and participant well-being.

Researchers are investigating treatments for adults with moderate to severe ulcerative colitis who have not responded well to steroids or other therapies. This Phase IV, randomized, open-label, multicenter trial aims to compare standard care with a treat-to-target approach using telemonitoring and patient education for those starting adalimumab (Humira4). The study will assess if home fecal calprotectin testing combined with e-monitoring and education improves patient outcomes by week 48. All participants will begin treatment with adalimumab at doses of 160 mg, then 80 mg, and 40 mg every other week until week 14, followed by 40 mg every other week until week 26. Based on patient and doctor preference, doses can be adjusted up to 80 mg every other week for two months and continued with azathioprine or methotrexate until week 38. Patients will also receive patient education sessions at weeks 0, 2, 14, 26, and 38, along with regular e-monitoring throughout the study. Participants will be followed for a total of 144 weeks across 20 sites in France. The main outcome is endoscopic remission at week 48, measured by an endoscopic Mayo score of 0. Additional assessments include clinical remission, steroid-free remission, healing rates, quality of life, patient satisfaction, safety, pharmacokinetics, hospitalizations, treatment adherence, and economic impact. Patients will report stool frequency, bleeding, and injection details via e-monitoring at multiple time points. This comprehensive monitoring aims to evaluate treatment effectiveness and patient engagement over time.

Critical Limb Ischaemia (CLI) is the final stage of arterial disease and a medical emergency where the outcome depends greatly on how quickly it is diagnosed. This condition is becoming more common and leads to high healthcare costs, making early diagnosis an important public health goal. Diagnosis usually combines symptoms like ischemic rest pain or necrotic wounds lasting more than two weeks with blood flow measurements such as ankle or toe systolic pressures or skin oxygen levels. Recent research emphasizes using pulsed Doppler ultrasound to analyze blood flow and measure the systolic rise time in foot arteries for better assessment of lower limb artery disease. The study evaluates a diagnostic method involving an arterial ultrasound scan of the lower limbs, including pulsed Doppler analysis of blood flow in the abdominal aorta, dorsal artery of the foot, and lateral plantar artery on both sides. This procedure aims to validate a reliable and accessible screening tool based on the maximum systolic rise time in foot arteries to identify patients with CLI early and refer them to specialized care centers. Participants will undergo ultrasound scans and measurements of systolic pressure at the toe as part of their evaluation. Researchers will monitor the diagnostic performance of the maximum systolic rise time over a 12-month period. The study focuses on patients with proven arterial disease, whether symptomatic or not, and includes follow-up assessments to confirm the tool's accuracy in detecting CLI and guiding timely treatment.

Cannabinoid hyperemesis syndrome (CHS) causes severe abdominal pain and vomiting in people who use cannabis regularly. It is often relieved by hot showers, which helps with diagnosis. The prevalence of CHS in France is not well known, but a previous study found a low rate among emergency patients with unexplained abdominal pain. Since cannabis is widely used in France, this study aims to estimate how common CHS is among patients visiting emergency departments in Maine et Loire for abdominal pain or vomiting. This is an observational, prospective, multicenter study enrolling adult patients aged 18 to 65 who come to emergency departments for abdominal pain or vomiting for the first time during the study period. Participants complete a questionnaire using a QR code or paper form while at the emergency department. Those who report regular cannabis use (at least weekly for 6 months) are followed up by phone three months later to check symptoms, recurrences, treatments, and cannabis use status. Researchers will measure how many patients are diagnosed with CHS after ruling out other causes. The inclusion period will last 12 months, with each CHS-positive patient followed for about 3 months. The study will also record medical treatments and symptom changes. The total study duration is 15 months, focusing on better understanding CHS incidence and patient outcomes in emergency settings.

Researchers are evaluating a new way to set mechanical ventilators for patients with acute respiratory distress syndrome (ARDS) to reduce death rates within 60 days. This trial includes adults with moderate to severe ARDS, whether caused by COVID-19 or other reasons, and compares a ventilation method based on lung mechanics to standard care. ARDS affects lung function severely, making ventilation challenging, and this study aims to find the best bedside ventilation approach to avoid further lung injury. The study has two groups: one where ventilator settings are personalized using bedside respiratory mechanics measurements like recruitability and airway closure, adjusting pressures to protect the lungs; and a control group receiving standard ventilation based on oxygen levels and standard protocols. Ventilation settings are carefully adjusted during the study, including volume control at specific levels and monitoring spontaneous breathing efforts. The design includes two sub-studies with shared procedures for both COVID-19 and non-COVID-19 ARDS patients. Participants will be monitored for 60 days to measure overall mortality. During the study, patients receive detailed assessments including breathing mechanics, oxygen levels, and ventilator parameters. Researchers track lung function and adjust treatments accordingly while ensuring safety limits. The trial collects data on how well the ventilation strategies protect the lungs and support recovery over this period.

Researchers are exploring a treatment approach for women with early-stage hormone receptor-positive, HER2-negative breast cancer who face an intermediate risk of cancer recurrence. This phase III trial builds on previous findings that adding the drug ribociclib, a CDK4/6 inhibitor, to standard hormone therapy after surgery can extend the time patients remain free from invasive disease. The study aims to see if using ribociclib allows some patients to avoid chemotherapy and its side effects without compromising treatment effectiveness. Participants will either receive chemotherapy followed by hormone therapy combined with ribociclib or a de-escalated treatment plan that reduces or omits chemotherapy while still using ribociclib and hormone therapy. Ribociclib will be administered for three years as part of the adjuvant treatment after surgery. The study is designed to reflect routine clinical practices for deciding chemotherapy eligibility, using standard pathological assessments and genomic tests. Throughout the trial, women will undergo regular monitoring, including clinical visits, laboratory tests, and heart function assessments, to ensure safety and treatment adherence. Researchers will measure invasive breast cancer-free survival over a period of up to 12 years from randomization. The study also tracks patients' ability to comply with treatment schedules and evaluates long-term outcomes to confirm if chemotherapy can be safely reduced or avoided in this group.

Researchers are investigating the clonal architecture of ASXL1-mutated primary and secondary myelofibrosis to better understand its impact on prognosis. This study addresses inconsistent findings in previous research regarding the prognostic value of ASXL1 mutations by analyzing clonal patterns in affected patients. The study plans to include a multicenter cohort of 50 patients diagnosed within the past 18 months. Participants will have their blood collected to determine clonal architecture using methods such as sorting circulating CD34 positive cells, cell culture, colony genotyping, and possibly single-cell DNA sequencing. A secondary analysis involves transcriptomic studies through RNA sequencing. This biological evaluation aims to provide detailed genetic insights related to ASXL1 mutations in myelofibrosis. During a 4-year follow-up as part of usual care, researchers will gather data on patient survival and any leukemic transformation. The primary outcome is to identify subgroups of ASXL1-mutated myelofibrosis based on clonal architecture over 24 months. The study will monitor disease progression and outcomes within the national clinical-biological database context.

Researchers are evaluating Trastuzumab deruxtecan (T-DXd) in adult patients with unresectable or metastatic HER2-low expressing breast cancer. This non-interventional study aims to assess the effectiveness of T-DXd, patients' demographic and clinical characteristics, treatment patterns, tolerability, management of adverse drug reactions, and patient experience. The study also collects data on conventional chemotherapy treatments in a disease registry to better understand treatment outcomes in this population. Participants will receive treatment with Trastuzumab deruxtecan or conventional chemotherapy drugs such as capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel according to the Summary of Product Characteristics and routine clinical practice. No study drug will be administered by the researchers, as treatments follow physicians' standard care decisions. This approach allows observation of real-world treatment use and outcomes. During the study, patients' treatment timelines and responses will be followed, focusing on the time to next treatment up to 31 months. Researchers will monitor tolerability, adverse drug reactions, and patient-reported experiences. Data collection includes clinical and demographic information, treatment patterns, and outcomes to provide a comprehensive understanding of T-DXd and conventional chemotherapy use in this patient group.

Researchers are evaluating the effectiveness of cotrimoxazole compared to the best standard antibiotic treatment for ventilator-associated pneumonia (VAP) caused by Enterobacteriaceae in adult patients admitted to intensive care units (ICU). This is a multicenter, randomized, non-inferiority Phase 3 trial aiming to show that cotrimoxazole is not worse than standard care in terms of patient survival 28 days after treatment begins. Participants must have a confirmed diagnosis of VAP with bacteria susceptible to cotrimoxazole. Patients are randomly assigned to receive either cotrimoxazole or the best standard antibiotic therapy, which may include beta-lactam or fluoroquinolone antibiotics. Treatment lasts for seven days, starting with an initial appropriate empiric antibiotic therapy. The dosing and administration of antibiotics are tailored according to current ICU guidelines. The trial is open-label due to variable antibiotic regimens in the control group. During the study, patients are closely monitored daily until death, ICU discharge, or 28 days after inclusion. Assessments include vital status, antibiotic use, new infections, and Clostridium difficile infections. Clinical signs and chest X-rays are reviewed on day 7 to evaluate cure. Weekly screenings for multidrug-resistant bacteria are performed until ICU discharge. The vital status is also checked at day 90, with follow-up contact for patients discharged before this time. An independent committee reviews the clinical and radiological outcomes without knowing the treatment assignments.