Saint Denis

Malignant hypertension is a very serious form of high blood pressure that can be fatal if untreated. This research aims to create the first large, multicenter database to better understand this disease, including its modern epidemiology, how patients are currently managed, and the diseases diagnostic criteria. The study will help improve knowledge and may lead to new treatment trials and evidence-based recommendations. The study is an observational registry enrolling patients diagnosed with malignant hypertension based on classic definitions, including severe blood pressure elevation and organ damage. It plans to recruit 500 patients and follow them for five years to study their prognosis and the impact of different patient characteristics and organ involvement. By collecting detailed data on disease features and care pathways, the study hopes to update definitions and management approaches. Participants will be observed over five years, with researchers collecting information on their health status, organ damage, and treatment. The main outcome measured is the five-year prognosis of patients. This long-term follow-up will provide detailed knowledge about the disease course and help identify factors influencing outcomes, without any study treatments or interventions being assigned.

Researchers are studying the impact and burden of three skin conditions moderate or severe alopecia areata, non-segmental vitiligo, and moderate to severe hidradenitis suppurativa. The study includes adolescents and adults and aims to understand how these conditions affect quality of life and daily functioning in a large global population. This is an observational study where participants with each condition will have a single visit for data collection following routine clinical practice. No experimental treatments are given instead, the study gathers information during this one visit to assess disease characteristics and impact. During the visit, participants will complete questionnaires and clinical assessments specific to their condition. These include tools measuring symptom impact, hair loss severity, skin depigmentation, and quality of life related to each disease. This helps researchers better understand the real-world burden of these conditions. Participation involves only this one visit, with no long-term follow-up or additional procedures.

Researchers are investigating the treatment outcomes of subcutaneous anifrolumab 120 mg given once weekly as add-on therapy to antimalarials, with or without glucocorticoids GCs, in patients with systemic lupus erythematosus SLE who have not previously received immunosuppressants or biologic therapies and are not in low disease activity status at enrollment. This Phase 3, multinational, open-label study aims to better understand remission rates, including DORIS remission, and the ability to taper and withdraw chronic GCs in this patient group. Participants will receive anifrolumab administered subcutaneously once weekly for 52 weeks using an autoinjector pen. The study includes a screening period of up to 35 days before treatment starts. For patients on higher doses of GCs at baseline, a structured tapering protocol will be followed from week 5 to week 40, aiming to reduce GC doses to 5 mgday and potentially withdraw GCs completely after sustained remission. After week 40, no further GC dose reductions will occur. An additional 12-week safety follow-up is planned for participants who discontinue anifrolumab after week 52. During the study, participants will undergo regular assessments including clinical evaluations, quality of life and fatigue questionnaires, and laboratory tests to monitor disease activity and remission status. Researchers will measure outcomes such as attainment and duration of DORIS remission, low disease activity, flare incidence, and changes in GC use. Safety will be monitored throughout treatment and in the follow-up period. The total study duration for participants is approximately 69 weeks, including screening, treatment, and safety follow-up.

This research aims to improve treatment and survival quality for infants, children, and young adults aged 0 to 45 years with acute lymphoblastic leukaemia ALL. It combines experiences from multiple European study groups into a master protocol that offers comprehensive risk stratification and treatment plans. The study includes randomized and interventional trials to identify therapies that may be less toxic and more effective, particularly focusing on reducing relapse and treatment-related side effects. Participants receive treatment based on a master protocol considered standard care, with additional randomized interventions testing modifications like reducing or omitting specific chemotherapy drugs such as Doxorubicin, Vincristine, and Dexamethasone. Some patients receive experimental treatments including Inotuzumab ozogamicin, Imatinib, 6-tioguanine, and Blinatumomab. Specific sub-studies also examine pharmacokinetics, neurocognitive outcomes, and cerebrospinal fluid diagnostics. The study design allows modular addition or stopping of sub-protocols and interventions. Throughout the study, participants undergo various assessments including monitoring of disease progression, side effects, and drug activity. Researchers evaluate event-free survival, disease-free survival, minimal residual disease response, and overall survival over multiple years, with follow-up periods extending up to 8 years. Participants cognitive functions and treatment toxicities are also assessed using specialized tests and questionnaires. Safety and adverse events are closely monitored to better understand treatment impacts over time.

Researchers are conducting an international clinical program to improve diagnosis, treatment, and understanding of childhood ependymoma in patients under 22 years old. The study aims to harmonize staging and care standards, assess biological markers, and develop treatment recommendations based on age, tumor location, and surgical outcomes. Patients are categorized into three groups based on residual disease and eligibility for radiotherapy to test different therapeutic strategies. The study includes three treatment strata Stratum 1 evaluates the impact of a 16-week chemotherapy regimen with VEC-CDDP after surgery and conformal radiotherapy in patients aged over 12 months to under 22 years with completely removed tumors. Stratum 2 examines the addition of high-dose methotrexate to VEC chemotherapy in patients with residual disease, followed by conformal radiotherapy and possibly an 8 Gy radiotherapy boost for inoperable residual tumors. Stratum 3 studies dose-dense chemotherapy with or without valproate in children under 12 months or those ineligible for radiotherapy. Patients not meeting these criteria enter an observational registry. Participants undergo centralized pathology and imaging reviews to confirm diagnosis and tumor resection status. Assessments include MRI scans, biological marker evaluations, and response to treatments. Researchers monitor progression-free survival, gross total resection rates, treatment response, neuropsychological and neuroendocrine effects, and safety over several years. The study involves scheduled visits, laboratory tests, and follow-up for up to five years to evaluate long-term outcomes.

Researchers are studying advanced non-small cell lung cancer NSCLC with ALK gene rearrangement treated with next-generation tyrosine kinase inhibitors TKIs as first-line therapy. This prospective study, part of the national EXPLORE ALK cohort, aims to understand the biological characteristics and resistance mechanisms of this cancer type. It involves patients with stage IIIB or IV NSCLC who are not eligible for curative locoregional treatment and have confirmed ALK rearrangement. The study collects tumor tissue samples at diagnosis and at disease progression, if available, to analyze ALK fusion partners, variants, and co-mutations using RNA sequencing. Blood samples are taken at diagnosis, first tumor evaluation, and disease progression to analyze circulating tumor DNA ctDNA with next-generation sequencing. Treatments studied include alectinib, brigatinib, lorlatinib, and entrectinib, either marketed or under early access programs. Participants provide blood samples and allow use of tumor tissue for centralized biological analyses. Researchers measure progression-free survival up to 72 months as the primary outcome, along with overall survival, response rates, duration of response, ctDNA clearance, and resistance mechanisms associated with treatment and ALK fusion partners. The study involves regular evaluations over several years to monitor treatment outcomes and biological changes.

Researchers are evaluating different antibiotic treatments for patients in intensive care units who have pneumonia caused by the bacteria Stenotrophomonas maltophilia. The study compares the effects of using one antibiotic monotherapy versus a combination of two antibiotics, as well as shorter 7 days versus longer 14 days treatment durations. This research also looks at how resistant the bacteria are to antibiotics and how often pneumonia recurs in these patients. The study involves observing patients who meet specific criteria without assigning new treatments directly. It focuses on the antibiotic strategies already being used, comparing their impact on patient survival. The main measurement is survival within 28 days based on the treatment strategy applied. There are no additional experimental interventions since this is an observational study. Participants will be adult patients who were hospitalized in a medical intensive care unit between January 1, 2018, and December 31, 2023, who were intubated and mechanically ventilated with ventilator-associated pneumonia caused by Stenotrophomonas maltophilia. The research team collects data on patient outcomes, antibiotic resistance, and pneumonia recurrence. The study aims to understand which antibiotic approaches may support better survival in this group.

Philadelphia-negative myeloproliferative neoplasms MPNs such as Polycythemia Vera, Essential Thrombocythemia, and Prefibrotic Myelofibrosis are chronic blood cancers caused by mutations affecting blood cell growth. These diseases carry a high risk of blood clots, which can cause serious complications and death. Current treatments include low-dose aspirin, but blood clots still occur in some patients despite therapy. This trial aims to study whether direct oral anticoagulants DOACs, which have shown benefits in other cancer patients, might help prevent blood clots in MPN patients with a specific mutation called JAK2V617F. Participants will be randomly assigned to receive either a direct oral anticoagulanteither Apixaban 2.5 mg twice daily or Rivaroxaban 10 mg once dailyor low-dose aspirin 100 mg once daily. The choice of DOAC is up to the investigator. The treatments will be given to high-risk patients for up to 24 months to compare their effects on clot prevention. Throughout the study, participants will be closely monitored for any thrombotic or bleeding events. During the trial, researchers will track the time until any arterial or venous blood clots occur, as well as any major or clinically relevant bleeding events. They will also evaluate survival, adherence to therapy, quality of life, and healthcare costs related to these treatments. Participants will have regular follow-ups over 24 months, including assessments for heart rhythm problems and safety monitoring. This comprehensive approach aims to better understand the benefits and risks of DOACs compared to aspirin in preventing clots in MPN patients.

This research focuses on adults hospitalized in the ICU with hospital-acquired sepsis caused by multidrug-resistant Gram-negative bacteria. It aims to compare different methods of giving beta-lactam antibiotics and the use of combination versus single antibiotic therapy. The study uses a 2x2 factorial design to evaluate these approaches for their impact on patient outcomes. Participants are randomly assigned to one of four groups that combine two antibiotic infusion strategies and two aminoglycoside dosing durations. The groups include continuous infusion of beta-lactam antibiotics with either a 5-day aminoglycoside infusion or a single dose, and intermittent beta-lactam infusion with the same aminoglycoside options. Treatment is administered according to the assigned group during the ICU stay. Throughout the study, researchers monitor patients for 30 days to assess mortality rates and kidney-related adverse events. Participants undergo bacteriological sampling before treatment and are followed with several clinical and microbiological evaluations, including infection status and organ function. The study tracks outcomes such as survival, kidney events, infection resolution, and length of ICU and hospital stay, with follow-up extending up to 180 days after inclusion.

Researchers are investigating treatment options for Diffuse Intrinsic Pontine Glioma DIPG and related diffuse midline gliomas with H3K28M mutation or similar molecular features. This phase 3, randomized, open-label trial compares the effects of ONC201 versus everolimus on progression-free survival. The study aims to determine whether ONC201 provides better outcomes than everolimus, focusing on patients including newly diagnosed DIPG and non-DIPG diffuse midline glioma cases. Participants are assigned to one of two treatment groups one takes everolimus tablets daily at a dose capped at 10 mg, and the other takes ONC201 capsules twice a week with dose limits. Both treatments continue until tumor progression, unacceptable side effects, or withdrawal of consent. Patients experiencing disease relapse may switch to the other treatment after a 7-day washout period. All patients also receive radiotherapy over six weeks, starting within weeks of biopsy or surgery, with options for reirradiation at progression. During the study, participants undergo central reviews of disease status, and treatment effects are monitored through clinical, radiological, and pathological assessments. Outcome measures include progression-free survival up to two years after the last patient joins, overall survival, complications from biopsy procedures, and safety profiles of the drugs monitored for up to five years. Participants health status and responses to treatments are regularly evaluated, ensuring careful observation throughout the trial period.