There are about 36633 clinical studies being (or have been) conducted in France. The country of the clinical trial is determined by the location of where the clinical research is being studied. Most studies are often held in multiple locations & countries.
Head trauma is a frequent reason for consultation in the emergency room. The CT scan is the reference examination allowing rapid management of the patient. However, CT examinations are among the diagnostic examinations with the highest exposure to ionizing radiation. The study investigators have previously implemented "ultra-low dose" (ULD) acquisitions for several pathologies with an effective dose level similar to that of a standard radiographic examination. These ULD acquisitions are now routinely used in our clinical practice for explorations of the thorax, spine, pelvis and proximal femurs, extremities. This study expands these ULD acquisitions to skull CT for detecting traumatic intracranial lesions. The study investigators hypothesize that it would be possible to search for intracranial lesions in patients with head trauma using ULD protocols, thereby reducing the doses delivered to the patient while maintaining sufficient image quality for the diagnosis.
The study is designed to evaluate the safety and efficacy of rusfertide in subjects with polycythemia vera (PV) in maintaining hematocrit control and in improving symptoms of PV.
The study duration of 4 years was considered to be sufficient to show a reliable and relevant effect of ocrelizumab on disability progression in the main study (CONSONANCE). However, given the potential long-term use of ocrelizumab in patients with progressive MS, it is critical that additional effectiveness and safety data are accrued in this patient population. In particular, understanding how ocrelizumab can prevent or delay time to major disability milestones such as the need to use an assisting device (Expanded Disability Status Scale [EDSS] 6.0) or a wheelchair (EDSS ≥7.0) is of significant relevance, given that progression to such milestones is associated with a significant reduction in patients' quality of life and an increase in cost of treatment (Kobelt et al. 2017). In the ORATORIO trial, ocrelizumab reduced the risk of 24-week confirmed EDSS ≥7.0 by 46% (hazard ratio [HR]: 0.54, 95% CI 0.31-0.92; p = 0.022) in patients with primary progressive multiple sclerosis (PPMS). To further characterize the potential long-term impact of ocrelizumab treatment on time to 24-week confirmed EDSS ≥7.0, an analysis was used to extrapolate the observed data into the future, estimating the time at which 50% of patients were expected to have reached EDSS ≥7.0. Extrapolated median time to confirmed EDSS ≥7.0 was 12.1 years for placebo, which was similar to the actual median time observed in MSBase (12.4 years), and 19.2 years for ocrelizumab, representing a 7.1-year delay (95% CI: -4.3 to 18.4) [Butzkueven et al 2021]. A recent MSBase analysis also showed that in a cohort of patients with secondary progressive MS (SPMS), 17.9% reached a confirmed EDSS score of 7.0 from the diagnosis of SPMS, over a period of approximately 12 years (Lizak et al. 2020). Therefore, following patients who complete CONSONANCE beyond the 4-year study period is justified, to better assess the impact of ocrelizumab on these long-term disability milestones. Another important therapeutic clinical goal in patients with progressive MS is preserving upper limb function. Patients with progressive MS with high EDSS scores, including those who are wheelchair-restricted, experience a devastating reduction in quality of life if they lose any residual function in their arms and/or hands, as this affects the level of independence and significantly limits the ability to perform activities of daily living (Kraft et al. 2014). The Nine-Hole Peg Test (9-HPT) has become one of the most frequently used measures of upper extremity function in MS (Earhart et al. 2011). A 20% worsening in test time is commonly used to define clinically meaningful worsening, as it corresponds to predefined clinically significant changes of established clinician- and patient-reported measures (Feys et al. 2017). Progression rates are lower for 9-HPT compared to EDSS or the Timed 25-Foot Walk Test (25FWT; Goldman et al. 2019). Therefore, following patients who complete CONSONANCE beyond the 4 year study period is justified, to better assess the long-term impact of ocrelizumab on preserving upper limb function. Patients with MS who have completed the CONSONANCE study, and have a favorable benefit risk ratio, as determined by the treating neurologist, can be included in this study if they meet the inclusion and exclusion criteria. 1.1. Study design This is a 4-year, single-arm, open-label, multicenter study for patients who have completed 192 weeks of treatment with ocrelizumab in the CONSONANCE study (NCT03523858), and enrolled under the protocol version 1 of CONSONANCE. It is estimated that the study will enroll approximately 90 patients with progressive MS. The study will consist of the following periods: 1. Screening period: The screening visit should be scheduled up to two weeks before the first infusion of ocrelizumab, and always after the last visit of CONSONANCE at Week 192. This period should not be exceeded. 2. Treatment period: The first visit of the treatment period (first infusion of ocrelizumab) will occur at the baseline visit, which should be 24 weeks (+14 days) after the last infusion of ocrelizumab in CONSONANCE. Ocrelizumab will be administered every 24 weeks up to Week 168 of this study. The last visit in the treatment period will be conducted 24 weeks after the last dose of ocrelizumab (i.e., at Week 192).
Immunotherapies have revolutionized medical oncology following the remarkable and, in some cases, unprecedented outcomes observed in certain groups of patients with cancer. However results in adults and mainly in pediatric cancer are still disappointing. Modulators of angiogenesis, such as VEGF, have a broad range of diverse effects on the immune system and the tumor micro-environment that are mainly immunosuppressive. In patients with early-stage disease, anti-VEGF therapy can lead to antitumor effects by modulating immune mechanisms - provided that therapy is maintained for an adequate length and tumors are sufficiently immunogenic. Nevertheless, blocking angiogenic molecules using a strategy based on a single therapeutic approach is likely insufficient to generate a complete or robust immune response against cancer, especially in patients with advanced-stage disease. Based on the results of previous studies which evaluated the safety profile of spartalizumab, of pazopanib and the combination of antiangiogenic agents with checkpoint inhibitors, a study combining spartalizumab and low-dose pazopanib in refractory or relapsed solid tumors of pediatric and adults is proposed. This study will include 2 separate cohorts: - the pediatric cohort will consist of a phase I study (dose-finding and expansion phases) combining pazopanib at a fixed dose of 225 mg/m2 and spartalizumab with four potential candidate doses (2, 3, 4 and 6 mg/kg). - the adult cohort will consist of a phase II study combining pazopanib at a fixed dose of 400 mg and spartalizumab at the RP2D of 400 mg every 4 weeks.
By inducing endogenous neuroprotection, hypoxic post-conditioning following stroke may represent a harmless and efficient non-pharmacological innovative neuro-therapeutic modality aiming at inducing neuroplasticity and brain repair, as supported by many preclinical studies. The investigators thus hypothesize that hypoxic post-conditioning represents a safe therapeutic strategy post-stroke. The investigators further hypothesize that hypoxic conditioning could enhance neuroplasticity and function in combination with conventional rehabilitative care. The primary study endpoint will be safety. Safety will be assessed through the clinical review of the adverse events over the duration of the study, every 48 hours by a trained evaluator, blinded for the therapeutic intervention. The investigators will further investigate the potential functional benefits of such a therapeutic approach on motor function, gait, balance, and cognition. The neurophysiological substrates of hypoxic conditioning-triggered neuroplasticity at a subacute delay post-stroke will also be investigated, based on biological and imagery markers.
Acute per-anesthetic hypersensitivity reaction (HSA-PA) is a rapidly occurring systemic reaction following injection of a drug during anesthesia (mortality between 3 and 9%). The substances responsible for these reactions in France are Neuro-Muscular Blocking Agents (NMBA) in 60% of cases. The main mechanism mentioned is an immediate systemic hypersensitivity immune reaction (anaphylaxis). The mechanism of immunization to NMBA is not yet understood. Electroconvulsive therapy (ECT) is a long-standing therapeutic approach still widely used today, for its high efficiency, particularly in depressive syndromes resistant to antidepressants. It has an efficacy comparable (or even superior) to pharmacological treatments and improves the mortality associated with this disease. Treatment with iterative ECT sessions includes an attack phase with an average of 12 sessions over 4 weeks, with secondary spacing of sessions before switching to antidepressant treatment. These sessions are carried out in the operating room under general anesthesia, thanks to a hypnotic and a NMBA, suxamethonium, as recently recommended by the French Anesthesiology Society in 2020. ECT therefore represent an interesting model of iterative exposure of a relatively homogeneous population to a single highly sensitizing substance, which could make it possible to study the evolution of sensitization as a function of various factors, in particular cumulative exposure, for which no data is currently available.
Seventy-eight percent of the population declares being concerned by pain, directly or indirectly. Chronic pain, defined as pain that has lasted for more than three months, affects more than one third of the French population. The national survey of the French Society for the Study and Treatment of Pain (SFETD), conducted in 2009, reveals that the most widespread chronic pain is low back pain (20%). Pain not only affects the body, but also destroys the person who endures it. A comparative study by Attal et al. carried out on a sample of 1,591 chronic pain sufferers and 1,237 non pain sufferers shows a major impact of pain on the individual's quality of life (SF12), sleep (MOS sleep) and anxiety and depression (HADS). The 2009 report of the French National Authority for Health (HAS) shows that chronic pain generates a significant societal cost. Low back pain is the leading cause of activity limitation in people aged 45 to 65, and the third leading cause of chronic disability. It is the leading cause of disability in people under 45 years of age, and the leading cause of work stoppage and occupational disease. The reference tool for assessing pain is currently the Visual Analogue Scale (VAS). However, several factors considerably limit the relevance of an exclusive use of this tool: - For the patient: the intensity of pain is objectively influenced by many parameters such as the time of day, stress, position, duration of evolution, mechanical or "neuropathic" character, paroxysms, etc. These are all elements that objectively disrupt the evaluation performed by the VAS. When the subjective and emotional dimension is included in these elements, the cloudiness of "true" perception of such a sensation increases even more. - Difficulties of evaluation for the carer: carers are therefore confronted with a lack of relevance of objective pain evaluation tools, and researchers have to deal with data that are often not very reproducible. A fortiori, the second problem arising from this concerns the difficulty of comparing the effectiveness of different therapeutic strategies. The VAS cannot, for example, take into account the pain dominance in the case of multi-site pain, nor the surface area of the pain zone or even less its typology or topology. This information is however essential to determine the choice of the most appropriate therapeutic strategy. - The difficulties of evaluation for the health care system: in fact, beyond the therapeutic wandering imposed on certain patients on a "micro" scale, it must be considered that this randomness of evaluation has an impact on the entire health care system. When a decision has to be made to reimburse a particular expensive drug or implantable medical device for pain relief, this reflection has to be extended to the "macro" level. This review thus reveals a threefold need for innovation in pain assessment: for the patient, for the caregiver and for the healthcare system.
Multiple sclerosis (MS) preferentially affects young adults with a female predominance. MS is not associated with an increased risk of complications or abnormal pregnancy outcomes. Nevertheless, disease-modifying therapies can have a teratogenic effect. Discussions about discontinuation should be made with a view to or upon discovery of pregnancy, taking into account the risk of untreated relapses and the risk of toxicity to the fetus. Natalizumab (NTZ) is a humanized anti-alpha4-integrin monoclonal antibody used as a treatment for highly active relapsing-remitting MS (RRMS). When it is stopped, there is frequent reactivation of the disease with possible relapses and a rebound effect could occur. At present, depending on the center, attitudes of neurologist may vary and 3 main scenarios can be observed: Pregnancy and postpartum under NTZ (group1), Pregnancy partially under NTZ (with or without immunomodulator (IM) supplementation, group 2), or NTZ stopped before pregnancy (with or without IM supplementation, group3). The first part of the BABYZUMAB study, a retrospective study of Natalizumab exposure during pregnancy, analysed the comparison the clinical activity of the disease (annualized relapse rate) according to these 3 scenarios of NTZ treatment The investigators analyzed the annual relapse rate (ARR) during a two-year period (9 months before and 15 months after the beginning of the pregnancy) in 117 patients identified in the OFSEP database. The investigators showed that the risk of relapses was four times higher in Group 2 versus Group 1 (p=0,014) and six times higher in Group 3 versus Group 1 (p=0,001). In the literature, there are few studies of newborns from NTZ-exposed pregnancies. No specific pattern of birth defects has been found, but mild to moderate transient thrombocytopenia and anemia have been reported in infants born to NTZ-exposed mothers in the third trimester of pregnancy.
Postpartum depression (PPD) may impair the mother-infant relationship and lead to both short and long-term suboptimal development of the baby. This study aims to evaluate the effectiveness of a targeted intervention (HUGS: Happiness Understanding Giving and Sharing) for enhancing the mother-infant relationship.
The understanding of ARVC pathophysiology remains incomplete. Several clues indicate that disease progression is mediated through inflammation. The present study aim to document the feasibility of detecting the potential presence of intracardiac local inflammatory components in patients with ARVC.