Lyon

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 evaluating the combination of CGT9486 and sunitinib compared to sunitinib alone in patients with locally advanced, unresectable, or metastatic Gastrointestinal Stromal Tumors GIST. This Phase 3, open-label international trial involves multiple parts, including dose confirmation, drug interaction assessments, and efficacy comparisons. The study also includes substudies focusing on drug-drug interaction potential and first-line treatment in patients with specific genetic mutations KIT exon 9. Approximately 482 patients will participate across these parts.

Researchers are investigating new treatment options for meningiomas that continue to grow despite local therapies like surgery or radiotherapy. This trial focuses on evaluating a precision medicine approach that combines PET-based imaging to select patients with tumors expressing somatostatin receptors and a targeted radioligand therapy called 177Lu-DOTATATE. This is the first randomized clinical trial studying this therapy in patients with meningiomas that have not responded to other treatments. Participants will be randomly assigned to one of two groups. One group receives 177Lu-DOTATATE through intravenous infusions every four weeks for a total of four cycles. The other group receives local standard care, which may include treatments like hydroxyurea, bevacizumab, sunitinib, octreotide, everolimus, or observation with supportive care, based on the investigators choice. This study is designed to compare the effects of 177Lu-DOTATATE against various standard treatments in this patient population. During the study, participants will undergo regular MRI scans to measure tumor size and progression. Researchers will also assess overall survival, neurological function, quality of life, and treatment side effects over a period extending up to two years after enrollment. Monitoring includes imaging, laboratory tests, and health questionnaires to evaluate how the disease and treatments affect participants over time.

Researchers are monitoring the use of the Virtue4 Male Sling System in men with stress urinary incontinence following prostate surgery. This observational study aims to collect medical data on the devices effectiveness and safety over 12 and 36 months after implantation. The study is conducted in multiple centers across Europe and focuses on real-world use by experienced urologists. The Virtue4 Male Sling is an implantable device made of polypropylene mesh designed to support the urethra and help manage urinary incontinence caused by intrinsic sphincter deficiency. This study involves men who have already received the sling during routine clinical care. Follow-up includes visits at baseline before implantation, between 1 and 3 months post-operation, and at 12 months, with additional annual questionnaires sent out at 24 and 36 months. Participants will undergo routine clinical assessments, including questionnaires about their urinary symptoms and quality of life, pad weight testing, uroflowmetry, and measurement of urine remaining after voiding at several points during the study. Researchers will monitor patient-reported improvement and any adverse events at 12 months. The study extends to 36 months with ongoing questionnaires to track long-term outcomes and satisfaction. Participation involves regular clinical visits and mailed surveys over three years.

Researchers are collecting detailed clinical and biological information from patients starting anticancer immunotherapy to better understand immune-related side effects that can affect various organs. The study aims to identify factors that increase the risk of these toxicities and to develop ways to prevent or manage them effectively. This observational study will help personalize future immunotherapy treatments by balancing benefits and risks for each patient. Participants receive immunotherapy drugs such as checkpoint inhibitors including PD-1, PD-L1, CTLA4, and others either alone or with other cancer treatments. Patients are enrolled before their first immunotherapy treatment and followed for up to 5 years or until they stop treatment permanently. The study also collects blood, plasma, serum, and immune cells samples before, during, and at the onset of immune-related side effects. During the study, participants will be regularly monitored through clinical evaluations and biological sample collections to track any immune-related toxicities. Researchers will estimate the incidence of these side effects over 10 years. Data collected will include clinical details and biological markers to support further research on mechanisms causing toxicity. This long-term follow-up helps improve understanding of immunotherapy safety and guides future patient care.

Researchers are evaluating new treatment options for people living with HIV-1 Human Immunodeficiency Virus Type 1 who have not been treated before. The current standard treatment, antiretroviral therapy ART, involves taking multiple medicines daily and may cause other health problems. This study aims to compare a new study ART combining two medicines, islatravir and ulonivirine, taken once a week, against the standard daily ART to see if it works as well and is safe and tolerable. Participants will receive one of several treatments for 96 weeks the study ART with islatravir and ulonivirine taken once weekly, the standard ART with bictegraviremtricitabinetenofovir alafenamide BICFTCTAF taken once daily, or combinations involving placebos matching these treatments. The study includes two phases Phase 2 which is open-label, and Phase 3 which is double-blind and randomized. During the study, participants will have regular assessments including measuring the amount of HIV-1 RNA in their blood and monitoring for adverse events and medication tolerance. Researchers will evaluate how well the treatments control the virus and affect immune cells over 24, 48, and 96 weeks. Safety monitoring will continue for about 102 weeks. The total study duration for participants is up to 96 weeks of treatment plus follow-up.

Researchers are investigating new treatment options for breast cancer that is hormone receptor-positive HR and human epidermal growth factor receptor 2-negative HER2-, specifically for cases that are unresectable locally advanced or metastatic. This type of breast cancer involves cancer cells that depend on hormones like estrogen or progesterone and have low HER2 protein levels. The study focuses on comparing the effects of patritumab deruxtecan against chemotherapy or trastuzumab deruxtecan in patients whose cancer has progressed despite prior treatments. Participants receive either patritumab deruxtecan through intravenous infusions every three weeks for about 13 months or a treatment chosen by their physician, which may include various chemotherapy drugs or trastuzumab deruxtecan, administered according to specific schedules for up to 13 months. The study is randomized and open-label, meaning participants are randomly assigned to one of the treatment groups, and both the patients and researchers know which treatment is given. Throughout the study, participants undergo regular assessments to monitor cancer progression and overall survival for up to approximately 85 months. Researchers evaluate tumor response, duration of response, and changes in quality of life using standardized questionnaires. Safety is carefully monitored by recording adverse events and treatment discontinuations. The goal is to understand if patritumab deruxtecan can improve outcomes compared to current treatment options.

Researchers are studying pulmonary arterial hypertension PAH, a condition where lung blood vessels become thick and narrow, causing high blood pressure in the lungs and making it hard for the heart to work. PAH can cause difficulty breathing and limit activity. While standard treatments help symptoms, they do not stop the disease from worsening. This research focuses on sotatercept, a targeted therapy aimed at specific proteins involved in PAH, to learn about its long-term safety and tolerability when added to usual PAH treatments. Participants in this long-term follow-up study, who previously took part in certain sotatercept trials, may continue receiving sotatercept by subcutaneous injection every three weeks. Those coming from blinded studies start at 0.3 mgkg with possible increases up to 0.7 mgkg, while those from unblinded studies continue their current dose with possible titration to 0.7 mgkg. The study monitors participants over an extended period to assess continued effects alongside their usual PAH therapy. During the study, participants will have regular assessments including monitoring for adverse events, blood tests for blood components and chemistry, body weight, blood pressure, and ECG readings. Researchers will also evaluate exercise capacity, heart function markers, and risk scores related to PAH. The study aims to follow participants for up to approximately 7 to 8 years to understand long-term safety, treatment tolerability, and health changes while using sotatercept with standard PAH care.

Researchers are evaluating the efficacy and safety of enicepatide, a dual GLP-1GIP receptor agonist, at multiple doses compared with placebo for weight management in adults with obesity or overweight and type 2 diabetes mellitus T2DM. This Phase III study aims to better understand how enicepatide affects body weight and other health measures in this population. Participants will be randomly assigned to receive either placebo or one of three dosing regimens of enicepatide, administered once weekly using an integrated drug-device combination product. The study lasts for 72 weeks, during which participants will self-administer the study drug or receive injections from a trained individual if needed. Throughout the study, participants will undergo various assessments including body weight, hemoglobin A1c, waist circumference, fasting glucose and insulin, cholesterol levels, blood pressure, and quality of life questionnaires. Safety will be monitored through adverse event reporting and specific rating scales. This comprehensive evaluation will help determine the effects of enicepatide on weight and diabetes management over the study period.

Researchers are evaluating new treatments for advanced ovarian cancer in women who have completed initial surgery and chemotherapy. The study focuses on non-HRD positive ovarian cancer, comparing a targeted therapy called sacituzumab tirumotecan sac-TMT given alone or with bevacizumab, against standard care options such as bevacizumab maintenance or observation. The goal is to see if sac-TMT with or without bevacizumab can help patients live longer without their cancer worsening. Participants in the experimental group will receive sac-TMT through intravenous infusion on days 1, 15, and 29 of every 6-week cycle until the cancer progresses, side effects become prohibitive, or other reasons for stopping arise. They may optionally receive bevacizumab on days 1 and 22 of each cycle. The comparator group will either receive bevacizumab alone every 3 weeks for up to 22 courses or be monitored without active treatment. Supportive medications like steroid mouthwash and other rescue drugs are recommended before sac-TMT infusions. Throughout the study, participants will be regularly monitored for how long they live without their disease progressing, overall survival, side effects, and quality of life using specialized questionnaires. These assessments will continue for up to approximately 78 months. The study is randomized, with single masking, and led by Merck Sharp & Dohme LLC. Participants can expect regular visits for treatment and monitoring during this period.