Ste Clotilde, France

Cardioverter DefIbriIlator PlacEMent for priMary Prevention of Sudden cArdiac Death in Patients Older Than 70 Years

Rationale Although not recognized by guidelines, there is no available data demonstrating the benefit of Implantable Cardioverter Defibrillator (ICD) for primary prevention strategy of Sudden Cardiac Death (SCD) in elderly. Nevertheless, ICD are currently implanted in this population by extending the results obtained in randomized trials involving younger subjects to the elderly. Finally, if the absence of implantation in the elderly was not inferior to the implantation of such a device, the non-implantation would avoid the device-related complications and decrease the health costs. Main objective The primary objective of DILEMMA study is to assess whether the "heart failure optimal therapy alone (HFOT)" strategy is non inferior to the "HFOT+ICD" strategy in terms of overall survival 48 months after randomization, in patients ≥ 70 years with an ICD indication for primary prevention of SCD whether there is an indication for cardiac resynchronization therapy or not. Design This is a 2-arm parallel non-inferiority, randomized, open label, multicenter trial. 730 patients will be included over 4 years. Follow up will last 4 years.

Pulmonary Vein Isolation Alone or in Combination With Substrate Modulation After Electric Cardioversion Failure

Atrial fibrillation (AF) is the most common heart rhythm disorder. It is the result of uncoordinated action of the atrial myocardial cells, causing rapid and irregular contraction of the heart's atria. The AF prevalence in adults is currently estimated to be between 2% and 4% and is expected to increase by a factor of 2.3 in the next few years, due to the increased longevity of the general population and the increased search for undiagnosed AF. Increased age is an important risk factor for AF, but other increased comorbidities, including hypertension, diabetes, heart failure, coronary artery disease, chronic renal failure, obesity, and obstructive sleep apnoea syndrome, are also important; modifiable risk factors contribute strongly to the development and progression of AF (ESC Guideline, 2020). The European Society of Cardiology (ESC) recommended pulmonary vein isolation (PVI) (Class IA) as first-line ablative strategy for persistent AF (Class IA) (ESC Guideline, 2020). However, PVI alone is only effective in treating about 40% to 60% of patients with persistent AF in the general population (unselected). If we apply this strategy to all patients (PVI alone), we accept to re-do ablative procedure in up to 60% of patients. The second feasible strategy is to treat patients with persistent AF by PVI combined with substrate modulation (ESC Class IIb). This strategy, when done well, by creating irreversible lesions (Marshall-PLAN) can effectively treat 70% to 80% of AF patients. But this implies that the investigator will be doing unnecessary substrate modulation in up to 40% of patients, which can lead to increased risks associated with the ablative procedure, longer procedure times, multiple lesions, etc… In addition, incorrect or incomplete substrate modulation is pro-arrhythmic and leads to recurrences in the form of left atrial flutters, tolerance of which, is generally poor. Both ablative strategies have been widely validated in large numbers of published studies. The problem is to know when and for which patients to apply one or the other of the two strategies. Electric cardioversion could help in selecting the most appropriate strategy.

Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare

This is a multi-center Phase 2/3 randomized, double-blind, placebo-controlled, parallel-group safety and efficacy study of dapansutrile (OLT1177®), a specific NLRP3 inhibitor, conducted in subjects with acute gout flare. Up to 300 eligible subjects will be randomized 2:1 to one of two treatment arms to receive either dapansutrile tablets or matching placebo twice daily for 7 days. An initial loading dose on Study Day 1 will be followed by a twice daily maintenance dosing regimen. Subjects presenting with acute gout flare that began within 96 hours prior to the Screening/Baseline/Day 1 visit will be evaluated for eligibility. Subjects who are determined to be eligible will be randomized into either an active treatment arm (2/3 of the subjects enrolled) or the placebo arm (1/3 of the subjects enrolled). Eligible subjects who are randomized into the study will also be provided with rescue medication at the Baseline/Day 1 Visit. No other pain medications, anti-inflammatory drugs (e.g., steroids or nonsteroidal anti-inflammatory drugs), or treatments for gout flare are allowed during the Treatment Period. During the Treatment Period, subjects will return to the clinic trial site on Day 4 and, following the 7-day Treatment Period, subjects will return to the clinical trial site on Day 8, and then Day 15 with safety data collected through Day 36.

CRYSTALILLE Cohort: Getting the Whole Picture of Crystal-related Arthropathies

All patients already included in another observational study set up in 2016 and meeting the eligibility criteria may be included in this study. An information letter will be sent to them by mail. If they wish to oppose to the use of their data, they can then return the objection form. This sample will be supplemented by new patients who are recruited during a classic rheumatology consultation. The investigator will propose the study to all patients meeting the inclusion and non-inclusion criteria. They will be informed of the objectives of the study and their rights. For patients who agree to participate in the study, sociodemographic and clinical characteristics will be collected. Depending on the usual care, they will benefit from an ultrasound and/or a dual energy scanner (M0). Imaging data will be collected. Routine clinical follow-up is then carried out in consultation, with collection of clinical and biological evolution data, and morphological data if necessary if imaging is rechecked, until the patient is lost to follow-up or the follow-up is interrupted at the GHICL for any reason. Available quarterly or semi-annual data will be collected.

One Day Implantation Program for Heart Failure Patients Implanted With CRT-P

The objective of the study is to show in the French centers selected for the same-day organization that a same-day CRT-P implantation is safe, feasible, and associated with significant cost-saving and a minimum conversion rate to full hospitalization by comparing outcomes with patients routinely hospitalized for at least one night. The medical economic evaluation will be based on the SNDS (National Health Data System) analysis.

BoStOn SCientific Rhythm MAnagemenT REgiStry (SOCRATES)

SOCRATES is a non-randomized, multisite, single-arm, open-label, global post-market observational data collection per standard of care. While generally of prospective design, a limited retrospective element is allowed for the inclusion of patients for a short period of 10 days after their index procedure. SOCRATES intends to enroll a number of subjects that will support the analysis of all the individual Post Market Clinical Follow-Up (PMCF) Plans. An average of approximately 100 subjects per year and site on a continuous basis is expected but may vary depending on the needs of individual PMCF Plans. As long as SOCRATES is active, there is no upper limit to the total number of subjects that may be enrolled, and enrollment will be driven by the need to support sample sizes of individual PMCF plans for given products/product groupings supported by SOCRATES. SOCRATES is designed to be a continuous effort after the data collection commences without a predefined closure timepoint. Data collection and enrollment may be stopped, restarted or finalized per Sponsor discretion. The expected duration of SOCRATES participation for a subject is dependent on - the specific lifetime of the device (e.g. the battery usage for pulse generators or continued active use of leads for CRM devices) or - the necessary timeframe to adequately assess safety and performance of the device based on the residual risk assessed for each device in the associated PMCF plan. Timeframes might e.g. spread from 7 days to one year post procedure for EP. The maximum duration per enrolled subject will consequently vary. For BSC implantable devices subjects are intended to be followed for the entire time of being implanted with a BSC device to allow data collection over the lifetime of the device(s) as required by applicable regulations. A maximum duration per enrolled subject is not defined, unless locally required. In case a local maximum duration is enforced subjects may be consented again and re-enrolled for continued participation if they are still in scope for SOCRATES. Sites shall ensure continuous data collection without any gaps in case a re-enrollment becomes applicable. Data sets for re-enrolled subjects will be handled as if the subject was continuously enrolled. This process will ensure to meet the requirement of MDR for device manufacturers to collect data over the lifetime of the devices.

Impact of Neuropsychological Disorders in Multiple Sclerosis

Therapeutic Adherence of Multiple Sclerosis Patients

Multiple sclerosis is a chronic and progressive disease that affects young adults (between 20 and 40 years old), impacting significantly the patients quality of life. The adherence to therapy affects the long-term functional clinical course (lower risk of relapses, reduction in disability progression and quality of life). The non-adherence rate to therapy in multiple sclerosis is estimated at 40%. The main identified causes of non-adherence are: forgetting to take treatment and adverse effects of drugs. Sociocognitive models as the Theory of Planned Behaviour (TPB) have been developed to help to understand and predict health-related behaviours. This model postulates that the intention to adopt a behaviour is one of the major determinants in the context of health. This intention comes from three independent elements : - Personal positive or negative attitudes towards the behaviour, - Social expectations or entourage perception (subjective norms), - Difficulty in accomplishing this behaviour (perceived control) Multiple sclerosis adherence to therapy studies have mainly focused on somatic variables (physical disability, illness duration, type of treatment) and some clinical variables (cognitive impairment, fatigue, depression). The few studies that have examined the multiple sclerosis therapeutic adherence determinants have mainly taken a one-dimensional perspective, such as perceived control. In the FELSA-SEP study, the role of sociocognitive factors (norms and beliefs, perceived threat to disease and health behaviours) and interpersonal factors (social support, patient-doctor relationship) will be explored.

Combination of Baricitinib and Anti-TNF in Rheumatoid Arthritis

Intensive combination therapies have revolutionised the management of solid neoplasms, hematologic malignancies, and acquired-immune-deficiency syndrome. These intensive strategies are based on the need to obtain rapid control of disease activity to afford the chance of stable full remission and avoid irreversible complications. The same goal applies to management of RA. Because current therapeutic strategies may fall short of these target goals and fail to improve quality of life in some patients, novel approaches are needed to improve outcomes. RA is a complex disease involving numerous cell types and inflammatory mediators of innate and adaptive immune systems. The investigators are aware that most of combination bDMARD strategies have been associated with little or no incremental benefit in efficacy compared to single-biologic therapy. However, our study will target mechanisms that differ from those in previous studies. Strategies that simultaneously target different pathways involved in the pathogenesis of RA may enhance treatment responses in patients with RA. Of note, baricitinib does not directly block signalling downstream of TNF, even if an indirect effect on TNF production is likely to occur. Targeting multiple inflammatory cytokines in combination may lead to more effective treatment and enhanced clinical responses in patients with RA compared to the current second-line strategies. The different mechanisms of action of baricitinib and anti-TNF, should ensure the efficacy of the combination. No concurrent trial evaluating similar strategies is registered at ClinicalTrial.gov.

Observation of Clinical Routine Care for Heart Failure Patients Implanted With BIOTRONIK CRT Devices