Athies, France

Product Surveillance Registry

Product Performance Report: Evaluate Long-term Reliability & Performance of Medtronic Marketed Cardiac Therapy Products

All Medtronic market-released leads and all market-released IPG, ICD and CRT devices are eligible to be included in this study.

Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG

This is a prospective, multicenter, open-label, randomized trial comparing OAC with no OAC (1:1 ratio) in patients who develop new-onset POAF after CABG. The primary effectiveness endpoint is the composite of death, ischemic stroke, transient ischemic attack (TIA), myocardial infarction (MI), systemic arterial thromboembolism or venous thromboembolism (VTE) at 90 days after randomization. The primary safety endpoint is BARC (Bleeding Academic Research Consortium) grade 3 or 5 bleeding at 90 days after randomization. The overall intent is to evaluate the trade-off in prevention of thromboembolic events versus an increase in bleeding. Patients will be randomly assigned to the following treatment strategies: - OAC-based strategy (experimental arm): OAC with vitamin K antagonist (VKA) with international normalized ratio (INR) target 2-3 or any approved direct oral anticoagulant (apixaban, rivaroxaban, edoxaban or dabigatran) in addition to background antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor) - Antiplatelet-only strategy (control arm): single antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor) The protocol-specified duration of anticoagulation is 90 days. Patients, who are randomized to the control arm and develop recurrent AF after 30 days, may be crossed-over to an OAC. Accrual is expected to take 60 months. Study follow-up visits will be performed at 90 days and phone follow-up at days 30, 60, and 180 days. Data for patients enrolled in the registry will be ascertained from the local clinical site via a review of medical records. The baseline risk profile of registry patients (i.e., patients eligible but unwilling to be randomized) will be analyzed and compared to that of patients randomized in the trial. The usage of anticoagulant and antiplatelet therapies in the registry population overall and baseline CHA2DS2-VASC ischemic stroke risk score will also be determined. Up to 500 patients will also be offered the option to participate in a digital health substudy which includes a wearable heart rhythm monitor device for 30 days post discharge.

Detection and Delineation of Necrotizing Fasciitis Via a Vascular Perfusion Fluorophore

Necrotizing fasciitis (NF)-commonly known as 'flesh-eating bacteria'-is an aggressive soft-tissue infection that has a high mortality rate (30-50%). NF is generally associated with traumatic inoculation of extremely aggressive bacteria into the soft-tissues surrounding the fascial layer of connective tissue, just deep to the subcutaneous fat. This tissue layer provides an ideal environment for bacterial growth and also facilitates rapid advancement of the bacteria along the fascia. The result is a soft-tissue infection that often spreads centrally prior to detection and/or adequate management, leading to systemic sepsis, multi-organ failure, and death. Further complicating NF management is that there is no definitive diagnostic test. Patients with NF present generally with pain, fever, and elevated inflammatory labs (white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)), other lab abnormalities (elevated glucose and creatinine; reduced sodium and hemoglobin); however, these are non-specific findings that are associated with numerous other-nonfatal-conditions. For this reason, a diagnosis of NF is often missed until the condition has progressed too far. Medical fluorescence is a nascent form of medical imaging that seeks to improve the recognition of important anatomical structures and disease processes through machine-assisted, visual identification using fluorescent probes called fluorophores. Several types of fluorophores exist: targeted fluorophores, enzyme-activated fluorophores, and simple intravascular fluorophores. Intravascular fluorophores, primarily indocyanine green (ICG), have been available for ~100 years. ICG is FDA approved and has an excellent safety record with no demonstrable toxicity. When injected intravenously and viewed with an appropriate fluorescence imager, ICG effectively maps out the local vasculature, enabling the viewer to distinguish perfused and non-perfused tissues. ICG's FDA-approved indications and uses include angiography to determine cardiac output, hepatic function, liver blood flow, and ophthalmic anatomy. Upon histological examination of tissues affected by NF, there exist four commonly observed features: 1) the presence of bacteria; 2) robust neutrophil infiltration; 3) tissue necrosis; 4) vascular thrombosis. DH-H Department of Pathology currently reviews tissue biopsies with respect to these criteria when evaluating tissue for the presence of necrotizing fasciitis (Soloman et al, Modern Pathology, 2018, pp 546-552). While useful to guide clinical decision-making, histological review is not considered to be a definitive diagnostic finding, but these observations do have moderate sensitivity and specificity with culture data, which is considered to be the ultimate determinant of an NF diagnosis. Because of the profound pro-thrombotic effects of necrotizing fasciitis within the subcutaneous tissues, we hypothesize that the administration of ICG and subsequent imaging of a bodily region affected with NF will demonstrate substantially reduced fluorescence compared to the patient's unaffected tissues. If we can demonstrate that ICG fluorescence voids are characteristic of NF, this could potentially lead to a more rapid, and potentially more accurate, diagnosis of NF that would lead to more rapid definitive management and-likely-improved outcomes. The goal of this pilot study is to evaluate whether ICG fluorescence may be used as a non-invasive method of identifying the presence of NF.

Study of INBRX-109 in Conventional Chondrosarcoma

This is a randomized, blinded, placebo-controlled, Phase 2 study of INBRX-109 in unresectable or metastatic conventional chondrosarcoma patients. INBRX-109 is a recombinant humanized tetravalent antibody targeting the human death receptor 5 (DR5).

Quantification of Visually Evoked Cortical Potentials in Individuals With Hearing Loss

Participants will schedule two appointments, at times convenient to the participant, to come to the testing clinic to complete the Visual Evoked Potential testing as well as the auditory test, cognitive/mood assessment battery, and sound quality survey included in this study. The first research appointment will include a test of the participant's vision that involves looking at a chart on a wall and identifying appropriate letters. After this brief visual test, the participant will complete VEP testing. For the VEP portion of the testing, participants will sit in a comfortable chair and have electrodes placed at several locations on their scalp. Electrodes are stickers that connect to a wire that connects to a computer. Electrodes do not break the skin or commonly cause any discomfort or harm. Participants will sit for approximately 1 hour and watch images presented to them on a computer screen while the participant's brain's response is measured using a computer. A picture of the electrodes on the participant's head will be taken for precise electrode localization. The second research appointment will consist of an auditory test, a cognitive/mood assessment, and a cochlear implant sound quality survey. The survey will only be completed by participants with a cochlear implant. The auditory testing portion will take place in the Audiology clinic and requires participants to listen and respond to different patterns of sound. While participants are at the clinic for testing, they will be asked to complete several questionnaires that ask about participant's mood and thought processing. Participants with cochlear implants will also be asked to complete a questionnaire about their perceived sound quality with their implant(s). The Visual Evoked Potential measure, auditory test results, cognitive/mood assessment, and cochlear implant sound quality survey responses will be compared between "hearing loss" and "normal hearing" groups to determine if VEP testing can be used in a new way to predict successful use of a cochlear implant or hearing aid.

Evaluation of a New Strategy for Protocolized Antibiotic Care for Severe Open Fractures: SEXTANT

Specific Aim 1: To compare the surgical site infection (SSI) rates of the current severe open fracture antibiotic strategy to a revised SEXTANT treatment strategy designed to address the modern wound bioburden at the time of wound closure or coverage. Specific Aim 2: To compare the terminal bioburden of the wounds at the time of definitive closure or coverage as sampled by standard tissue microbiology. Specific Aim 3: To compare rates of antibiotic-related serious adverse events (SAEs) of the two treatment groups. Exploratory Aim 4: To pilot the use of available and emerging rapid PCR platforms for wound pathogen identification in a sub-cohort of patients.

Topical Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures At High Risk of Infection: TOBRA

Specific Aim 1: Compare the proportion of deep surgical site infections (SSI) of the study injury within 182 days of definitive fracture fixation surgery in patients allocated to receive a combination of local Vancomycin and Tobramycin powders compared to patients allocated to local Vancomycin powder. Sensitivity Analyses: A series of sensitivity analyses will be conducted to look at alternative measures of deep SSI under Specific Aim 1. These sensitivity analyses will consider the following alternative end points of deep SSI: infection by gram-negative bacteria, infection by gram-positive bacteria, polymicrobial pathogenic infections, culture negative infections, and cellulitis/skin infections. Specific Aim 2: To compare the safety of treatment with a combination of local Vancomycin and Tobramycin versus Vancomycin powder alone as measured by the proportion of antibiotic resistance in each arm.

Study of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in the First-line Treatment of Subjects With Advanced or Metastatic NSCLC Without Actionable Genomic Alterations

The primary objective of the study is to compare the efficacy of Dato-DXd and pembrolizumab with pembrolizumab alone in terms of either Progression Free Survival (PFS) by BICR or Overall Survival (OS) for participants with advanced or metastatic NSCLC with non-squamous histology without actionable genomic alterations whose tumor has high programmed death-ligand 1 (PD-L1) expression (tumor proportion score; TPS ≥50%) and who have not previously received systemic therapy for advanced or metastatic NSCLC. Eligible participants will be randomized in a 1:1 ratio to the control arm (pembrolizumab alone) or the experimental arm (Dato-DXd and pembrolizumab). The study will be divided into 4 periods: Tissue Screening Period, Screening Period, Treatment Period, and Follow-up Period.

ABTECT - Maintenance

All eligible subjects who have completed either one of the induction studies above mentioned, will be given the opportunity to take part in the present ABX464-107 study which consists of 2 treatment phases. This study consists of a 44-week maintenance treatment phase (Part 1 and Part 2), followed by a 4-year Long Term Extension (LTE) treatment phase and a 28-days follow-up period consisting in the End of Study (EOS) visit. The maintenance phase is a 44-week double blind, placebo-controlled, phase. Subjects who are clinical responders after 8 weeks induction will be randomized to Part 1, and those who are non-clinical responders will be randomized to Part 2. At the end of the 44-week maintenance phase, subjects will continue their allocated treatment until the maintenance phase is unblinded. Once the study is unblinded, all subjects receiving obefazimod will continue their allocated treatment. Subjects receiving placebo will be allocated to obefazimod 25 mg or can terminate the study.