There are about 93 clinical studies being (or have been) conducted in Monaco. 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.
The investigators hypothesize that patients with mild TBI and normal TCD can be safely discharged home immediately after the ED. The targeted population is the category of patients eligible for early discharge: 1) patients with mild lesions on the initial CT scan and a GCS 15 after CT scan completion and, 2) patients with no lesion on the initial cerebral CT scan with at least one of the following risk factors: GCS 14 after CT scan completion, persisting post-traumatic nausea/vomiting/headaches, concomitant alcoholic intoxication or patients treated with aspirin. The study will not include mild TBI patients who are not eligible for early discharge: patients with no possibility of home supervision, those with a GCS lower than 14 after the CT scan or those treated with anticoagulant/antiplatelet drugs other than aspirin. The investigators expect the TCD-based strategy to be non-inferior compared to the standard strategy according to French recommendations in terms of the 3-months neurological outcome. From a public health standpoint, the use of TCD as a triage tool may change current guidelines regarding mild TBI management.
Overall survival (OS) of patients with advanced (stage IIIB/IV) non-small-cell lung cancer (NSCLC) remains short after the first line of treatment with a median OS of 12.2 months in non squamous NSCLC and 9.2 months in squamous NSCLC . In this setting the programmed death 1/ligand 1 (PD-1/-L1) were targeted with nivolumab (IgG4) in advanced squamous and nonsquamous NSCLC leading to an increase of the 1-year OS rate of approximately 10-15% in both histologies. Nivolumab, pembrolizumab and atezolizumab are now considered a standard of care in 2nd line advanced NSCLC and in 1st line for pembrolizumab but but prognosis still remains poor in advanced NSCLC. Overall survival (OS) of patients with advanced (stage III/IV) NSCLC remains limited with a median OS of 12.2 months in non-squamous NSCLC and 9.2 months in squamous NSCLC if anti-PD1 alone. It is of around 16 months if pembrolizumab is combined with chemotherapy. Preclinical data indicates that anti-tumor efficacy is increased when anti-PD-1/-L1 are combined with irradiation (IR). Radiotherapy alone can elicit tumor cell death which can increase tumor antigen in the blood stream, favoring recognition by the immune system and its activation against tumor cells outside of the radiation field (="abscopal effect"). IR may also reverse acquired resistance to PD-1 blockade immunotherapy by limiting T-cell exhaustion. Because of these preclinical and clinical data several studies analysing the combination of IR and anti-PD1 in NSCLC are ongoing. Among them, two studies are testing the administration of IR and nivolumab in stage III NSCLC: the NCT02768558 phase III trial (RTOG), and the NCT02434081 phase II trial (ETOP). Antonia et al [2017] tested the use of anti-PD-L1 after chemoradiotherapy in unresectable stage III NSCLC. Median time to distant metastasis was increased (23.2 months vs. 14.6 months, p<0.001). An increase of OS is consequently expected. However, no study involving concurrent RT and pembrolizumab combined with chemotherapy in advanced NSCLC is ongoing, which is the purpose of the present study, NIRVANA-Lung.
To obtain data for the Rhythmia™ Mapping System in conjunction with Boston Scientific Open-Irrigated (OI) Catheters for ablation of Paroxysmal Atrial Fibrillation (PAF) according to current international and local guidelines. Primary objective: To assess acute and long-term outcomes for the Rhythmia Mapping System in conjunction with Boston Scientific Open-Irrigated Ablation Catheters to treat de novo Paroxysmal Atrial Fibrillation. De Novo PAF is defined as subjects undergoing first ablation procedure for PAF with no prior left atrial ablation (RF, Cryo, Surgical).
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterized by inflammatory arthritis and enthesitis involving the spine. AxSpA prevalence is around 0.17% of the French population. Tumor necrosis factor (TNF) was the first target defined in axSpA. Since one third of axSpA patients failed to the first TNF blocker, many axSpA patients received a second biological Disease-Modifying AntiRheumatic Drugs (bDMARDs). Until few months, the only choice was to use a second TNF blocker.Since 2003, pharmaceutical companies investigated efficacy of TNF blockers already used in rheumatoid arthritis. Etanercept is a fusion protein with TNF receptor type II p75 and IgG1 Fc fragment, whereas adalimumab, infliximab, and golimumab are monoclonal antibodies. Certolizumab is a fusion between a fab fragment targeting TNF and a Peg fraction. All demonstrated efficacy versus placebo in a randomized double blinded study In case of failure to the first TNF blockers, rheumatologists will follow the "Treat-to-Target" principle. This approach already demonstrated its benefit in rheumatoid arthritis or in psoriatic arthritis. This concept was also suggested for axSpA with low levels of evidence and recommendation. So rheumatologist will provide the best treatment in case of failure to the first TNF blockers, which is a daily clinical situation. Since few months, rheumatologists have the choice between targeting IL-23/17 axis compared to a second TNF blocker.
Brain injury is a frequent purpose for consultation in emergency services. Management of brain injury is time and resource consuming, combining clinical monitoring and imaging. The stage prior to the management of the victims of brain injury is stratification of the severity, potential or proven. Severe brain injury requires emergent brain CT-scan, ideally within one hour of the first medical contact. Patients requiring this strategy present with focused neurological deficit, Glasgow score <15 to 2 hours after the trauma, suspicion of open fracture of the skull or dish pan fracture, any signs of fracture of the skull base (hemotympanum, bilateral peri-orbital ecchymosis), otorrhea or rhinorrhea of cerebrospinal fluid, more than one episode of vomiting in adults, and posttraumatic convulsion. Patients benefiting from anticoagulant therapy are included in this category. Victims of brain injury that do not fall into this category are considered less critical. By definition, mild traumatic brain injury : - a trauma of the cephalic extremity : - whose Glasgow score (30 min after the trauma or during the consultation) is 13-15, - associated with one or more of the following: confusion; disorientation; loss of consciousness of 30 min or less; post-traumatic amnesia of less than 24 hours; other transient neurological abnormalities (focal signs, epileptic seizures, non-surgical intracranial lesion). Among these patients, some are considered at risk of developing intracerebral lesions. Nevertheless, it should be noted that the prevalence of hemorrhagic complications is radically different between patients with a Glasgow score of 13 and those with a score of 15. Thus, the recommendations suggest a brain scan without injection of contrast media within 4 to 8 hours for patients with the following characteristics : - a retrograde amnesia of more than 30 minutes, - a loss of consciousness or amnesia associated with: - either a risk mechanism (pedestrian overturned by a motor vehicle, ejection of a vehicle, falling by more than one meter), - or an age> 65 years, - or coagulation disorders, including the use of platelet aggregation therapy. Patients who fall outside this definition are considered low risk of complication and should not benefit of imaging. Data from the scientific literature show that an early brain CT-scan allows identification of post-traumatic lesions in this population. Nevertheless, organizational problems, including the availability of the imaging, radiation, and disruption of surveillance related to patient displacement, are limitations to this strategy. In contrast, the low cost-effectiveness of CT scan is often advocated in patients with mild traumatic brain injury. For example, in the Octopus study, 52 of 1316 patients who received CT scan after mild head trauma had an intracerebral lesion. Among these patients, 39 (3%) had intracerebral lesion related to trauma; for 13 (1%) patients, the link with the trauma was uncertain. In fact, the search of alternatives for a safer, more conservative, more efficient practice, one of the objectives of which is to limit the undue use of cerebral scanning. Thus, many teams have been interested in the use of biological variables to guide the decision to use imagery. Among candidate biomarkers, the S100B protein has been the subject of many evaluations which allow it to be used in current practice. Indeed, the increase of the S100B protein carried out within 3 hours following a mild head trauma makes it possible to identify the patients at risk of intracerebral lesion and to target the indications of imaging. The purpose of the registry is to describe the use, interpretation and performance of the S100B protein in its use at bedside in emergency medicine.
The objective of the study is to demonstrate the non-inferiority for clinical efficacy of an endovascular treatment strategy with the MitraClip® in comparison with a surgical treatment strategy in patients with severe primary mitral regurgitation judged eligible for anatomical repair with the MitraClip® or mitral valve surgery with high surgical risk. This trial is a French and Monegasque, multicenter and randomized trial. Patients enrolled will be clinically followed for 2 years ( clinical visit at 1 month, at 6 months and 12 months, phone call at 18 months and clincial visit at 24 months).
The objective of the RHAPSODY study is to evaluate the performance of new software features in subjects undergoing standard of care catheter-based endocardial mapping for atrial or ventricular tachyarrhythmias using a commercial Rhythmia Mapping System. Results from this study will be used to guide development and refinement of new software features that may be implemented in future commercial software releases.
Biological markers of depressive states have been studied, but their usefulness to predict the therapeutic response is unknown. This issue is major in all depressive states which have not remitted after several lines of treatment. rTMS (repetitive transcranial magnetic stimulation) is a non-pharmacological alternative in the treatment of depression, but its effects on cerebral functioning are not known in episodes which have resist to conventional treatments. The investigators will include 50 depressive patients who have failed to respond to two successive antidepressant medication, and propose them a treatment with low frequency rTMS during 3 to 6 weeks. Cerebral functional imaging with 18FDG-PET (positon emission tomography) with be assessed at the beginning and at the end of rTMS acute treatment, in order to measure induced metabolic changes and their correlation with clinical states. Patients who have responded to rTMS acute treatment may continue this therapeutic for six months, and the investigators will assess if efficacy maintenance is related with cerebral metabolic variations
This project aims to provide the proof of concept for transcranial direct-current stimulation (tDCS) in the treatment of resistant/persistent Schizophrenia symptoms. The purpose is to investigate the effect of tDCS on symptoms in schizophrenic patients demonstrating a partial response to a first frequently prescribed antipsychotic medication. An early optimization of the therapeutic strategy must constitute an important factor for prognosis. Hypothesize is that tDCS should alleviate symptoms in patients depending on the clinical characteristics. In this study, stimulation is an add-on treatment to antipsychotic medication, and will be used in a broad variety of patients, i.e. in patients with varied durations of illness, various symptoms profiles, and various levels of treatment response. This in turn will allow the determination of the extent to which results can be generalized to varied patient populations, as well as the extent to which various therapeutic targets (e.g. different symptom dimensions, cognitive performance and brain connectivity) may be improved with tDCS. Despite interesting preliminary results, our team is unable to describe optimal non-invasive brain stimulation (NIBS) response markers. This study is a randomized, double blind, controlled, French multicenter study (11 centers). The investigators plan to include 144 patients with persistent symptoms in schizophrenia. Seventy two subjects will receive active tDCS and 72 subjects will receive sham tDCS (placebo). Hypothesize is a lasting effect of active tDCS on the schizophrenic symptoms as measured by the number of responders, defined as a decrease of at least 25% of symptoms as measured by a standardized clinical scale score (PANSS) between baseline and after the 10-session tDCS regimen. Furthermore, the participants believe that an in depth understanding of the cortical effects of tDCS could constitute an important step towards improving the technique and developing treatment response markers. An analysis of the effects on cortical activity and plasticity markers could be an interesting approach.
Sepsis is a constant concern in ICU, frequent and severe, it requires early diagnosis and prompt implementation of the etiological treatment. The bacterial infections are the most common and are associated with high morbidity and mortality. Diagnosis is based on the detection of micro-organisms (bacteria) that can confirm the diagnosis and to tailor antibiotic treatments. Blood cultures are positive in 30-35% of cases and diagnosis is often based on a body of evidence that the use of biomarkers. No biomarkers (or even a combination of biomarkers) no evidence to confirm or refute the diagnosis of sepsis alone. During sepsis, gram + and gram - are circulating and often present in small amounts; they can be detected by sensitive and specific tools following a pretreatment of the blood sample (innovative technology Bacti-DIAG). The main objective of the multicentre study Bacti-DIAG-Rea is testing in prospectively, in a suspicious population resuscitation of sepsis, this new bacterial biomarker. Secondary objectives will assess whether Bacti-DIAG provides time and precision gain (gram + vs grams) in the patient's care including diagnosis and treatment. All ICU patients and with clinical criteria of Systemic Inflammatory Response Syndrome (SIRS) sepsis suspects will be included: in addition to the samples taken for routine care of the patient 4 tubes of whole blood will be collected 5mL. The definitive diagnosis of sepsis or SIRS be confirmed retrospectively by two independent experts blinded to Bacti-DIAG. The areas under the ROC curves for the detection of gram + and gram will be calculated and associated detection limits will be determined to meet the objectives of the study. It is planned to include 400 consecutive patients with SIRS criteria for sepsis 300-360 and analyze biometric and biological data based on the subsequent evolution of the patients. The care of patients will be blinded to the results of the new biomarker Bacti-DIAG