Nancy

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 new treatments for advanced renal cell carcinoma RCC that has returned after prior therapy. The study aims to find out if the combination of belzutifan and zanzalintinib can help people with recurrent advanced RCC live longer without their cancer worsening compared to the drug cabozantinib. This is a phase 3 randomized trial evaluating these treatments in participants who have experienced recurrence during or after prior anti-PD-1L1 therapy. Participants are randomly assigned to receive either belzutifan plus zanzalintinib taken orally once daily or cabozantinib taken orally once daily. They continue their assigned treatment until certain reasons require stopping the study intervention. The study compares the effects of these treatments on cancer progression and survival among people with advanced RCC who have had disease recurrence after adjuvant therapy. During the study, participants will be regularly monitored for progression-free survival and overall survival for up to about 73 months. Researchers will also assess tumor response, duration of response, adverse events, and quality of life using questionnaires over approximately 25 months. The study involves ongoing evaluations to understand how these treatments affect symptoms, functioning, and overall health during long-term follow-up.

Food Protein Induced Enterocolitis Syndrome FPIES is a type of non-IgE mediated food allergy that usually occurs in infancy and is often not well known by clinicians. The study aims to collect clinical information and allergy test results from children diagnosed with the acute form of FPIES and to observe their condition over three years. It seeks to better understand the evolution of FPIES, including atypical forms, with no prior prospective data available from France. Children diagnosed with acute FPIES will be followed in this national prospective study conducted at sixteen French centers. Allergy tests such as oral food challenges, skin prick tests, and IgE blood tests will be used for diagnosis and monitoring. Patients will be seen at an initial visit and then annually for up to three years. If tolerance to the offending food is not acquired, an oral food challenge will be performed in the hospital for confirmation. Participants will undergo yearly allergist visits for evaluation of symptoms and allergy testing. Researchers will measure the rate of tolerance acquisition to foods over one, two, and three years post-inclusion, as well as the progression to IgE sensitization and clinical IgE-mediated allergy. Additional outcomes include the presence of multiple FPIES episodes and related atopic conditions. The study will provide insights into the natural history and management of FPIES in children.

Researchers are conducting a prospective, multicenter cohort study to follow children with idiopathic nephrotic syndrome INS, a rare kidney disease. The study aims to collect data on pediatric patients treated by pediatric nephrologists in France and its overseas territories to better understand the diseases characteristics and support future clinical trials. The study involves regularly recording medical, biological, psychological, and social data through routine clinical follow-ups, hospitalizations, and consultations. Additionally, annual telephone interviews will be conducted for patients in remission. Quality of life, treatment adherence, and treatment impact questionnaires will also be collected. A biobank is established to collect blood, urine, hair, and nail samples at the disease onset before immunosuppressive treatment begins. Participants will be followed from disease onset until age 18 or transfer to adult nephrology care. Data is collected via a secure website, medically validated and entered by clinical research staff. The main outcome is the number of cases included and their characteristics over two years. Participation involves routine care visits, interviews, and questionnaires, with continued monitoring planned through the study period ending in 2048.

Researchers are evaluating intravenous brincidofovir IV BCV compared to intravenous cidofovir IV CDV for treating adenovirus infection in children and adults who have received allogeneic hematopoietic cell transplants allo-HCT. This Phase 3, multi-center, randomized, open-label study focuses on patients with adenovirus viremia, aiming to assess the effectiveness of these treatments in clearing the virus. The study uses a virologic response-driven approach to determine treatment duration, following ECIL guidelines for high-risk patients. Participants will be randomly assigned to receive either IV BCV or IV CDV. Treatment will continue until adenovirus DNA in plasma is undetectable for two consecutive tests spaced 7 days apart or until a maximum of 12 weeks of therapy is reached, whichever occurs first. Subjects who clear the virus may stop treatment but can be retreated with their assigned drug if adenovirus viremia recurs at defined levels. The study prohibits switching between the two drugs. Safety will be monitored by an independent board during enrollment. Throughout the study, participants will be assessed weekly until the end of treatment, with additional evaluations at 4 weeks after the last dose and at 12 and 24 weeks post-randomization. Researchers will collect plasma samples to measure drug concentrations and monitor viral response and safety. All participants will be followed for a total of 24 weeks regardless of treatment duration, ensuring comprehensive monitoring of efficacy and safety during and after therapy.

Researchers are evaluating the use of stereotactic radiotherapy SRT as a treatment strategy for patients with oligoprogressive metastatic renal cell carcinoma RCC who are already undergoing systemic therapies. This phase II study focuses on patients whose cancer has progressed in a limited number of sites despite ongoing treatment, aiming to control local tumors and delay the need for additional systemic therapies. The study builds on evidence that SRT can effectively target RCC metastases and may also stimulate the immune system when combined with immunotherapy. The study involves delivering high-dose stereotactic radiotherapy to metastatic sites showing progression in patients receiving systemic therapies such as targeted drugs or immunotherapy. Eligible patients have 1 to 3 progressing metastases in up to 2 organs, with lesions measuring 4 cm or less, and will continue their current systemic treatment while receiving SRT either concurrently or sequentially. This approach aims to locally control progressing tumors and potentially extend the effectiveness of ongoing therapy. Participants will undergo imaging assessments to confirm disease progression and measure tumor response, with follow-up visits to monitor tumor control and treatment side effects. Researchers will evaluate progression-free survival six months after randomization as the primary outcome, along with local and overall control rates and treatment-related adverse events. The study includes monitoring for safety and effectiveness up to 12 months post-treatment, with participants involvement lasting until at least one month after treatment completion.

Researchers are evaluating the effectiveness, safety, and tolerability of camizestrant combined with ribociclib in patients with advanced ER-positive, HER2-negative breast cancer who have not received any prior systemic treatment for their advanced disease. This Phase IIIb global, multicenter, single-arm study aims to provide insight into this combination therapy as a first-line treatment option. Participants will receive daily oral tablets of camizestrant 75 mg and ribociclib 600 mg at standard doses continuously until they choose to stop treatment or it is discontinued for any reason. Approximately 150 participants will be enrolled and treated within this trial. During the study, participants will be monitored for treatment effectiveness using time to next treatment, time to discontinuation, and progression-free survival over a two-year period. Safety will be assessed by tracking adverse events, including any severe toxicities within the first six months. Participants will undergo regular assessments related to organ function and performance status throughout the treatment period, which may last until discontinuation.

Barrett Esophagus is a condition where the esophageal lining changes, increasing the risk of developing precancerous tissue and adenocarcinoma. This study compares two treatment methods for Barrett Esophagus complicated by dysplasia the new EndoRotor system versus the established Radiofrequency ablation. The aim is to evaluate the effectiveness of these treatments in eradicating Barrett Esophagus and associated dysplasia. The study is randomized and controlled, conducted by the University Hospital, Angers. The EndoRotor system mechanically removes the esophageal mucosa in one session through a device that cuts and aspirates tissue, allowing for histological analysis after treatment. Radiofrequency ablation uses thermal energy to destroy the abnormal mucosa, typically requiring multiple sessions with a debridement step using acetylcysteine spray before ablation. Participants are randomly assigned to receive either EndoRotor or Radiofrequency treatment. Both methods aim to fully eradicate Barrett Esophagus tissue but differ in technique and potential costs. Participants will undergo endoscopic evaluations before and after treatment, with biopsies taken to assess the presence of Barrett Esophagus and dysplasia at 3 and 12 months post-treatment. Safety assessments include monitoring discomfort, pain, and adverse events for up to 3 months. The study also evaluates the quality of tissue samples for pathological analysis, treatment cost-effectiveness, and the number of additional treatment sessions needed. Total participation may last up to a year, with multiple follow-up visits to monitor treatment success and safety.

This trial is a Phase 2 study evaluating axatilimab, an antibody targeting the colony stimulating factor 1 receptor, in participants aged 2 years and older with recurrent or refractory active chronic graft versus host disease cGVHD. These participants have previously received at least two lines of systemic therapy but still have active disease requiring further treatment. The study aims to assess the efficacy, safety, and tolerability of axatilimab at different dose levels in this population. Participants will be randomly assigned to one of three axatilimab dosing regimens administered intravenously. The doses include 0.3 mgkg every two weeks, 1 mgkg every two weeks, or 3 mgkg every four weeks. Treatment cycles last 28 days and may continue for up to two years. This open-label, multicenter study allows participants to receive axatilimab while being closely monitored. During the study, participants will have regular assessments to evaluate treatment response based on established NIH criteria for cGVHD. Researchers will measure overall response rates in the first six cycles as well as throughout the study period of up to two years. Other evaluations include symptom scales, organ-specific responses, medication use changes, laboratory biomarkers, and safety monitoring. Participants are followed for efficacy, tolerability, and adverse events during treatment and for the full study duration.

Researchers are evaluating BHV-7000 as a treatment for adults with refractory focal onset epilepsy, a form of epilepsy that does not respond to standard anti-seizure medications. The study aims to determine if BHV-7000 can reduce seizure frequency and assess its safety and tolerability. This Phase 23 clinical trial is sponsored by Biohaven Therapeutics Ltd. and involves participants aged 18 to 75 years with a diagnosis of focal epilepsy lasting at least one year and resistant to previous treatments. The trial consists of two parts. In Part A, participants are randomly assigned to receive either 25 mg or 50 mg of BHV-7000 once daily or a matching placebo. After completing Part A, participants may enter Part B, which involves randomization to either 75 mg of BHV-7000 once daily or placebo. Both parts are blinded, meaning neither participants nor researchers know who receives the active drug or placebo during the treatment periods. Participants will keep accurate seizure diaries throughout the study to track seizure frequency. Researchers will monitor safety by recording adverse events and laboratory abnormalities from Week 8 to Week 20 in both parts. The main outcome measured in Part B is the change in average seizure frequency over 28 days compared to baseline. Secondary outcomes include the percentage of participants with significant seizure reduction and seizure freedom during the study. The total participation duration includes treatment and follow-up assessments over several weeks.