Dax

Myeloproliferative Neoplasms (MPN) are blood cancers linked with a higher risk of blood clots, involving platelets, red blood cells, white blood cells, and blood vessel cells. Some studies have looked at the JAK2V617F gene mutation in white blood cells to predict clot risk, but results have been mixed. This research aims to study the amount of this mutation in different blood cell types and blood vessel cells to find patterns that may relate to clot risk in MPN patients. The study will include 120 patients with polycythemia vera (PV) or essential thrombocythemia (ET) who have the JAK2V617F mutation. Blood samples will be taken to isolate platelets, red blood cells, granulocytes, and endothelial cells. The mutation level will be measured in these cells using digital PCR technology. Researchers will explore how these patterns connect to clot history at diagnosis, MPN type, clot risk scores, and clot types. Participants will undergo a special blood draw alongside routine tests. The study will analyze the mutation levels in different cells and their association with clot risk and disease characteristics. The main measurement is the history of thrombosis when the disease is diagnosed. Safety and consent procedures are followed, and patients will be included at diagnosis or within one year without prior cytoreductive treatment, with consent and registry inclusion.

Researchers are evaluating the effect of early sitting out of bed in an arm-chair position on the functional recovery of patients in intensive care who are on mechanical ventilation. The study focuses on patients with ICU-acquired weakness and aims to determine if this early mobilization technique improves functional and muscular recovery compared to a conservative strategy of sitting in bed. The research hypothesis is that early armchair positioning enhances functional recovery. Participants will be placed in a chair once awake with a Richmond Agitation-Sedation Scale (RASS) score between -1 and +1 for more than 12 hours. They will be seated daily for at least 30 minutes until discharge from intensive care or day 28, whichever comes first, unless there are temporary contraindications. If patients cannot communicate their wish to stop, their tolerance will be checked, and the chair session will not exceed 4 hours. During the study, researchers will assess participants' functional levels at discharge from intensive care or day 28, whichever occurs first. Patients will be monitored throughout their stay, and adherence to the intervention will be tracked. The total participation duration varies depending on the length of stay in intensive care, with functional recovery as the primary outcome measure.

Ventilator-associated pneumonia (VAP) is a common and serious infection in intensive care units, often leading to prolonged mechanical ventilation and excessive antibiotic use. This trial evaluates two strategies for starting antibiotic therapy in patients with suspected non-severe VAP: immediate antibiotic treatment after sampling versus waiting for microbiological confirmation before starting treatment. The study aims to balance the risks of unnecessary antibiotic exposure against the dangers of delaying therapy in infected patients, considering concerns about antibiotic resistance and patient outcomes. Participants are randomly assigned to one of two groups. The control group receives immediate empiric antibiotic therapy within one hour of randomization, based on clinical judgment and local protocols; treatment is stopped if respiratory samples are negative or continued for seven days if VAP is confirmed. The conservative strategy group waits for respiratory sample culture and/or PCR results before starting antibiotics; if results are negative, no antibiotics are given, and if positive, treatment is started promptly and continued for seven days without waiting for susceptibility testing. Throughout the study, participants are monitored for death or continued use of invasive mechanical ventilation up to 28 days. Researchers record the proportion of patients who die or remain on ventilation at 28 days as the primary outcome. The study involves patients who have been mechanically ventilated for more than 48 hours and meet specific clinical criteria for suspected VAP without signs of severe illness, with informed consent obtained from patients or their representatives.

Researchers are investigating treatments for locally advanced anal squamous cell carcinoma, a rare but increasing cancer often linked to human papillomavirus (HPV). The study compares standard chemoradiotherapy, which combines radiation and chemotherapy with 5FU and mitomycin-C, to a new approach adding induction chemotherapy (modified DCF protocol) before the standard chemoradiotherapy. This randomized phase 3 trial aims to improve disease-related event-free survival and other outcomes such as overall survival, colostomy-free survival, treatment tolerability, response rate, and quality of life in patients with T3-T4 or N1 stage anal cancer without metastasis. Participants in the experimental group receive four cycles of induction chemotherapy (docetaxel, cisplatin, and 5-FU given every two weeks), followed by standard chemoradiotherapy consisting of 33 sessions of radiation over 6.5 weeks combined with mitomycin during weeks 1 and 5 and capecitabine taken on radiation days. The control group receives only the standard chemoradiotherapy. Radiation is delivered using intensity-modulated external irradiation (IMRT-SIB) targeting the pelvis and tumor area with specified doses. During the study, patients undergo follow-up visits starting 8 weeks after treatment, then every 4 months for two years, and every 6 months for a final year. Follow-up includes clinical exams and imaging tests such as CT and MRI. The study measures disease-related event-free survival at 2 years after treatment completion as the primary outcome. Participants must be adults aged 18 or older with measurable tumors on MRI and able to receive chemotherapy and radiotherapy, with additional health criteria assessed before enrollment.

Colorectal cancer mainly affects elderly patients, with over half of new cases in France occurring in those aged 70 or older. Adjuvant chemotherapy has shown benefits in disease-free and overall survival after stage III colon cancer surgery, but its use in elderly patients remains limited. This phase III randomized study explores whether adjuvant chemotherapy improves disease-free survival in elderly patients and which chemotherapy regimen is most effective, addressing concerns about benefits for both unfit and fit elderly patients. Participants will be divided into two groups based on a multidisciplinary evaluation including a geriatrician. One group will receive fluoropyrimidine-based chemotherapy (LV5FU2 or capecitabine), and the other will receive oxaliplatin-based chemotherapy (FOLFOX4 or XELOX). Some patients may be assigned to observation only. Treatments will begin within 12 weeks after surgery. The study also evaluates specific biological markers common in elderly tumors, such as mismatch repair deficiency. During the study, participants will undergo assessments including geriatric questionnaires and medical monitoring. Researchers will track disease-free survival over three years following the last patient's enrollment. Safety and treatment effects will be monitored, with exclusion of patients expected to live less than four years or those unable to comply with follow-up. The study aims to better understand chemotherapy benefits in an elderly population after colon cancer surgery.

Researchers are evaluating a range of treatments to improve outcomes for adults admitted to intensive care units (ICUs) with severe community-acquired pneumonia (CAP), including cases caused by influenza and COVID-19. This Phase 3 adaptive platform trial, REMAP-CAP, is designed to test multiple treatment strategies simultaneously and adapt over time, allowing new treatments to be added as questions are answered. The trial also serves as a platform to quickly evaluate treatments during respiratory pandemics, such as COVID-19, through a sub-study called REMAP-COVID in the United States. Participants receive various interventions including antibiotics like ceftriaxone, moxifloxacin, or piperacillin-tazobactam, as well as macrolide therapies given for different durations. Other treatments assessed include corticosteroids such as hydrocortisone and dexamethasone, antiviral agents like oseltamivir and remdesivir, immune modulators including tocilizumab and baricitinib, and supportive care strategies such as mechanical ventilation methods. Dosing and duration vary for each treatment, with some interventions now closed. Treatments are administered according to local guidelines and clinical decisions, with some requiring intravenous or enteral routes. Participants are closely monitored with assessments focusing on survival and organ support status in the ICU up to 90 days after enrollment. The main outcomes measured include all-cause mortality by day 90 and the number of days alive without needing organ support in the ICU by day 21. The study collects data continuously to adapt treatment assignments for new participants, aiming to identify the most effective therapies. Follow-up and safety monitoring continue throughout hospitalization and up to 90 days after admission.

Researchers are studying the long-term health outcomes of people living with HIV who are treated with antiretroviral therapy (ART). While ART has helped make HIV a chronic condition with survival rates close to the general population, those living with HIV still face higher risks of other health problems, including immune system issues, cardiovascular disease, cancer, and complications from aging. The study also looks at psychiatric, neurological, and social factors affecting these individuals, aiming to better understand overall health beyond just physical symptoms. Participants in this study receive follow-up care based on national guidelines, where demographic, clinical, biological, and treatment data are collected at each hospital visit using a standardized questionnaire. All health events are recorded according to the International Classification of Diseases (ICD-10). Additionally, a biobank of samples is collected from consenting participants at entry and every two years thereafter to support further research. People in the study will be monitored for up to four years, with annual assessments of socio-demographic characteristics and health status. The study tracks the development of new health problems, monitors the effectiveness and side effects of ART regimens, and gathers comprehensive data on participants’ clinical management. This long-term observation aims to provide a detailed understanding of morbidity and mortality risks in treated HIV patients.

This research aims to evaluate the safety and effectiveness of itacitinib for treating systemic sclerosis (SSc) in adults. SSc is a rare autoimmune disease causing skin fibrosis, inflammation, and blood vessel problems, which can lead to serious organ involvement and disability. The study focuses on the diffuse form of SSc, which is linked to more severe symptoms and shares similarities with graft versus host disease. The trial builds on evidence showing that blocking the JAK-STAT pathway, involved in fibrosis, may help reduce disease activity. Participants will receive either itacitinib or a placebo, both given as 200 mg oral doses daily for 360 days. Itacitinib is a Janus kinase inhibitor targeting JAK1 to reduce fibrosis-related signaling. The trial is a Phase II, randomized, controlled study comparing the effects of itacitinib to placebo over one year. Treatment begins after screening and continues for the full 360 days. During the study, participants will be regularly monitored through clinical assessments, including the modified Rodnan skin score (mRSS) to measure skin fibrosis changes over 360 days. Safety and disease activity will be tracked with laboratory tests and evaluations. Participants must give informed consent and meet strict eligibility criteria. The total involvement spans the entire treatment period with ongoing follow-up to assess outcomes and safety.

Researchers are evaluating the safety and quality of outpatient care compared to conventional hospital care for patients with acute uncomplicated appendicitis who undergo laparoscopic appendectomy. The study focuses on whether same-day discharge is as safe and effective as staying overnight in the hospital. This approach aims to improve patient satisfaction, reduce hospital stays, lower healthcare costs, and limit exposure risks during situations like the COVID-19 pandemic. The trial compares two treatments: ambulatory appendectomy, where the surgery is done in an outpatient unit and patients leave the hospital the same day, and conventional appendectomy, where patients stay overnight under observation after surgery in a digestive surgery department. Patients included are those with confirmed uncomplicated appendicitis and meet specific health and monitoring criteria, such as having a relative available for monitoring after discharge and living close to a hospital. Participants will be followed for 30 days after surgery to monitor overall safety and recovery. Researchers will assess complications, health status, and any morbi-mortality events during this period. The study includes careful screening before surgery, ongoing safety monitoring, and uses imaging and laboratory tests to confirm eligibility and health status. The total participation period covers the surgery day and 30 days of postoperative follow-up.

Researchers are evaluating strategies to manage the withdrawal of denosumab treatment in women with postmenopausal osteoporosis. Denosumab withdrawal may cause a rebound effect, leading to increased bone turnover, loss of bone density, and a higher risk of vertebral fractures. This Phase 4 study aims to compare two approaches using zoledronate (ZOL) infusions to reduce this rebound effect and protect bone health after stopping denosumab. Participants receive an initial infusion of ZOL 5 mg six months after stopping denosumab. One group receives a second ZOL infusion only if a bone turnover marker called crosslaps reaches a certain level, indicating insufficient bone resorption control. The other group receives a standard treatment with a possible rescue second infusion at month 12 if there are signs of fractures or high risk. This open-label, randomized trial compares the effectiveness of these two zoledronate strategies over one year. During the study, participants have their lumbar bone mineral density measured after one year to assess bone health. Researchers monitor bone turnover markers like crosslaps to guide treatment in the biomarker-driven group. Safety and treatment outcomes, including fracture occurrence, are tracked throughout. Participants are involved in regular assessments to understand how well the strategies maintain bone density and reduce fracture risk after denosumab discontinuation.