Baggiovara-modena, Italy

Study to Investigate Comparative Efficacy, Safety and Immunogenicity Between AVT16 and Entyvio

The study will consist of a screening period, a treatment and assessment period and an End of Study visit. Eligibility for the study will be determined during a screening period. Subjects who meet the eligibility criteria will be randomised to either AVT16 or Entyvio.

A Prospective Observational Study of Video Laryngoscopy Versus Direct Laryngoscopy for Insertion of a Thin Endotracheal Catheter for Surfactant Administration in Newborn Infants

Many newborn infants have breathing difficulty after birth, particularly when they are born prematurely. Many of these infants are supported with nasal continuous positive airway pressure (NCPAP). Some of the infants deteriorate despite treatment with NCPAP and have a thin catheter inserted into their trachea for the administration of surfactant, which is then immediately removed (often referred to as "less-invasive surfactant administration" or LISA). Insertion of a thin catheter is usually performed by doctors who are experienced at intubation (i.e. inserting endotracheal tubes, ETTs). They look directly into the the infants mouth using a standard laryngoscope to identify the opening of the airway (i.e. perform direct laryngoscopy). More recently video laryngoscopes have been developed. These devices display a magnified image of the airway on a screen that can be viewed indirectly by the doctor attempting to insert the ETT or thin catheter, and also by others. A single centre study reported that more infants were successfully intubated at the first attempt when doctors performed indirect video laryngoscopy compared to direct laryngoscopy. It is possible to independently verify when a doctor has correctly inserted and ETT, for example by detecting carbon dioxide coming out of the tube or seeing condensation in the tube during exhalation, or by hearing breath sounds by listening to the chest during positive pressure inflations. It is not possible to independently verify whether a doctor has correctly inserted a thin catheter under direct laryngoscopy, by these or other means. The standard (and to date only) way of confirming that a thin catheter has been correctly inserted is to rely on the report of the operator. Video laryngoscopy, in contrast, allows the independent verification of the tip of a thin catheter by one or more people observing the screen. The investigators are performing NEU-VODE, a stepped wedge cluster randomised study of the introduction of video laryngoscopy versus direct laryngoscopy for the intubation of newborn infants. Alongside this study, the investigators are performing a study of infants who have a thin endotracheal catheter inserted under video laryngoscopy versus direct laryngoscopy. As it is not possible to measure the outcome of successful insertion of the thin catheter equally in both groups, this is a prospective observational cohort study. The investigators will record information on infants who have a thin catheter inserted into the trachea for the purpose of surfactant administration at centres participating in the NEU-VODE study. The type of laryngoscope used for thin catheter insertion attempts will not be mandated; instead, the investigators will compare the information of groups within the cohort who have their first attempt made using the video laryngoscope to the group who have their first attempt made with direct laryngoscopy.

A Stepped Wedge Cluster Randomised Trial of Video Versus Direct Laryngoscopy for Intubation of Newborn Infants

INTRODUCTION Many newborn infants have difficulty breathing after birth. Some of these babies have a tube inserted into their "windpipe" (trachea) - an endotracheal tube (ETT) - through which they are given breathing support (ventilation). When clinicians attempt to intubate (insert an ETT), they use an instrument called a laryngoscope to view the airway in order to identify the entrance to the trachea (larynx). Standard laryngoscopes have a "blade" (which, despite its name, is not sharp) with a light at the tip. Doctors insert the blade into the baby's mouth to view the larynx. Traditionally, clinicians used a standard laryngoscope to look directly into the baby's mouth to view the larynx (direct laryngoscopy, DL). When clinicians attempt to intubate newborns with DL, less than half of first attempts are successful. Also adverse effects - such as falls in the blood oxygen levels (fall in oxygen saturation (SpO2), or "desaturation"), slowing down of the heart rate (bradycardia), oral trauma - are relatively common. In recent years, video laryngoscopes (VL) have been developed. In addition to a light, VL have a video camera at the tip of the blade. This camera acquires a view of the larynx and displays it on a screen that the clinician views when attempting intubation (indirect laryngoscopy). In a randomised study performed at the National Maternity Hospital, Dublin, Ireland, more infants were successfully intubated at the first attempt when clinicians used VL compared to DL [79/107 (74%) versus 48/107 (45%), P<0.001]. While this study was large enough to show that VL resulted infants being successfully intubated at the first attempt in one hospital, it couldn't give information about how it might work in a range of hospitals, and it wasn't large enough to see what effect VL had on adverse events. There is a large difference in cost between a standard laryngoscope (approx. €300) and a video laryngoscope (approx. €21,000). This is a matter of concern for all hospitals, particularly in settings where resources are more limited. The investigators aim to assess whether VL compared to DL results in more infants being intubated at the first attempt without physiological instability. STUDY DESIGN A recent single centre study reported that that more newborn infants were successfully intubated at the first attempt when VL was used to indirectly view the airway compared to DL. This study was not large enough to determine the effect of VL on adverse effects that are seen commonly (e.g. desaturation) or more rarely (e.g. bradycardia, receipt of chest compressions or adrenaline, oral trauma) during intubation attempts. For the current study, the investigators chose a stepped-wedge cluster randomised controlled design, where the participating centre, rather than the individual infant, will be the unit of randomisation. This design has been found appropriate to test the effects of an intervention that encompasses a behavioural aspect and to implement interventions while studying them at the same time. In this study, all centres will begin in the "control group"; where clinicians will routinely attempt intubation with DL, as is their usual practice. At specified intervals, centres will be randomly assigned to cross over to the "intervention group", where clinicians will routinely attempt intubation with VL. All participating centers will have included patients in both arms by the end of the study. SAMPLE SIZE ESTIMATION To determine the intra-cluster correlation (that means the correlation between two observations from the same centre), the investigators used the dataset of the MONITOR trial that included infants from 7 delivery rooms worldwide. In this trial, the intra-cluster correlation for intubation in the delivery room was reported as 0.1. This complete stepped-wedge cluster-randomized design includes 21 time periods (including the baseline) and 20 centres that will be including patients, with each randomised to a unique sequence. Each time period lasts a fortnight. Each time period, 1 centre will switch their treatment from DL to VL. With all centres including 2 patients each time period, 42 patients will be included per centre which will provide a total sample size of 840 patients. Assuming a control proportion of 0.4, this sample will achieve 90% power (0.9091) to detect a treatment proportion of 0.55, assuming a conservative ICC of 0.05. The power is not very sensitive to ICC values up to 0.1 (power of >90% to detect difference 40% versus 56%). The test statistic used is the two-sided Wald Z-Test. TREATMENT OF SUBJECTS DIRECT LARYNGOSCOPY (DL, control period) At the start of the study, clinicians at participating centres will attempt intubation using a standard laryngoscope to perform DL as is their normal practice. VIDEO LARYNGOSCOPY (VL, intervention period) For each centre, a lot will be drawn which indicates the month in which endotracheal intubation will be routinely attempted with VL rather than DL. In the month before the switch, centres will be provided with a C-MAC VL by the manufacturers, Karl Storz-Endoskop (Tuttlingen, Germany). The system will be provided on loan for the duration of the study and will consist of an 8" high-definition monitor with connecting cable and reusable straight Miller type blades size 0 and size 1. The equipment will be demonstrated by representatives from Karl Storz, and clinicians who intubate babies at participating hospitals will be encouraged to practice with the equipment on mannequins. We will have an virtual meeting with each centre in the week before they are due to switch to review the protocol, data collection and to answer any queries that they may have. All other procedures in the delivery room and NICU will be performed according to international and local guidelines. All other aspects of the approach to intubation at the participating centre are at the discretion of the local clinicians and should remain the same for the duration of the study; e.g.: - The drugs used before intubation attempts (e.g. opiate, atropine, curare-like drug) - The route by which intubation is usually attempted (i.e. oral or nasal) - Whether they use a stylet is routinely used - Whether supplemental oxygen is given during attempts

Southeastern Europe Microcirculation Registry

The study will include adults of both sexes older than 18 years with angina symptoms or angina equivalent referred to cath lab for evaluation of coronary artery disease (CAD) that underwent invasive physiology testing performed (microcirculation testing +/- vasospasm testing) using Coroflow Coroventis Cardiovascular system (Abbott Vascular, Abbott Park, IL, USA) The study will exclude persons under the age of 18, pregnant of nursing ant the ones where no coronary physiology measurements performed . The following data will be collected at enrollment: - De-identified demographic data - Cardiovascular risk factors and significant co-morbidities - Laboratory investigations of interest - Prior cardiovascular events - Pre-procedure medications - Echocardiogram within 3 months of invasive coronary procedure - Non-invasive ischemia testing within 3 months of invasive coronary procedure - Seattle Angina Questionnaire (SAQ) - EQ-5D-5L - Details of the coronary angiography and invasive physiology procedure including procedural complications - Post-procedure medications Data that will be collected during invasive coronary physiology testing: Vasospastic angina testing (which artery, what test, result) Microvascular angina testing (which artery, CFR, IMR, RRR, FFR, Pd, Pa and all transit times) Patients will be seen at follow up visits and the following data will be collected every 6 months for up to 5 years: - Major adverse cardiovascular events including repeat invasive coronary angiography since last follow up - Current medications - SAQ - EQ-5D-5L - Non-invasive ischemia testing since last follow up Outcomes will be evaluated every 6 months for 5 years via direct patient contact by research staff or at follow up visits. Outcomes will be collected based on existing medical documentation. Primary outcomes: - all-cause death and non-fatal MI - composite MACE: all-cause death, non-fatal MI, coronary revascularization, hospitalization for cardiovascular causes (acute coronary syndrome, heart failure, angina, repeated coronary angiography) Secondary outcomes: all-cause death, cardiovascular death, MI, coronary revascularization, stroke, hospitalization for heart failure, hospitalization for acute coronary syndrome, repeated coronary angiography Patient-centered outcomes: - Freedom from angina (SAQ questionnaire) - Quality of life using EQ-5D-5L questionnaire - Follow up non-invasive ischemia testing (if performed)

A Trial to Evaluate the Efficacy and Safety of Tralokinumab in Combination With Topical Corticosteroids in Children and Infants With Moderate-to-severe Atopic Dermatitis

Study of Navtemadlin Add-on to Ruxolitinib in JAK Inhibitor-Naïve Patients with Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib

H. Pylori Screen-and-treat Study in a Population of Young Adults

The main objective of this study is to assess the feasibility of population-based H. pylori test-and-treat strategy for gastric cancer prevention in Europe. The study will allow to assess the feasibility of implementing H. pylori test-and-treat program in an early 30's age group at the population level, which will be carried out for the first time in Europe. This will come with scientifically valid assessment of programme processes, acceptance, effectiveness and possible adverse consequences. The assessment of predefined quality indicators and achievements of each project task will consequently allow us to scale up the project to the national level, for example, by instituting a national program for gastric cancer prevention with population-based H. pylori test-and-treat program in the asymptomatic population around 30 years of age in different EU countries. The implementation of this strategy as a national program could result in significantly reduced gastric cancer incidence, disease burden and costs of other H. pylori-related diseases in the medium and long term in Slovenia and other participating countries, thus serving as a model for the implementation of this strategy in Europe. The results of the study can help to guide other EU countries with intermediate and high gastric cancer incidence when implementing similar strategies. The results can also help to guide EU countries with low gastric cancer incidence when implementing similar programs for their subpopulations at risk (e.g. family members of patients with gastric cancer and immigrants from countries with high H. pylori infection and gastric cancer incidence). If implemented in a young adult population, the program can prevent further spread of H. pylori infection by curing the infection before or when they have just started their own families, therefore reducing the risk of intrafamilial transmission. As shown in previously published economic evaluations of the strategy, the program is not only cost-effective in gastric cancer prevention but also in other high-risk areas. Besides that, H. pylori eradication will also prevent other serious clinical complications, such as peptic ulcers, dyspepsia, primary immune thrombocytopenia and anaemia caused by H. pylori infection. In total, seven research centers from different European countries participate in the study - Croatia, Ireland, Latvia, Poland, Romania, and Slovenia. A predefined population of young people between 30 to 34 years of age will be invited to participate in the study. Based on signed informed consent they will be offered testing for H. pylori infection. Acceptability and participation rate of the H. pylori test-and-treat strategy, the prevalence of H. pylori infection in the population of young adults, compliance with the 14-days treatment scheme, the eradication rate, and any adverse effects of the treatment in the population will be thoroughly assessed. Testing and treatment procedure will be substantiated with data about early childhood risk factors for H. pylori infection and the use of tobacco and alcohol consumption. Method used for capturing the participants' self-reported data will be a questionnaire administered by a health professional or self-administered by the patient. Each center has its own specific research design: 1. Clinical Hospital Center Rijeka (KBC Rijeka), Croatia: 13C-urea breath test (UBT) confirmatory testing combined with H. pylori serology will be determined. H. pylori positive patients will be treated by bismuth-based quadruple therapy (Protocol I): • Protocol I with penicillin includes the following medications: Antibiotic 1 - Amoxicillin 4 x 500 mg or Clarithromycin 2 x 400 mg, Antibiotic 2 - Metronidazole 4 x 400 mg, Proton pump inhibitor - Esomeprazole 2 x 40 mg, Colloidal bismuth - Bismuth oxide 4 x 120 mg. In case there will be a treatment failure after Protocol I is completed, the remaining patients with a positive infection will be referred to a secondary treatment (Protocol II): • Protocol II includes the following medications: Antibiotic 1 - Levofloxacin 1 x 500 mg, Antibiotic 2 - Metronidazole 4 x 400 mg, Proton pump inhibitor - Esomeprazole 2 x 40 mg, Colloidal bismuth - Bismuth oxide 4 x 120 mg. All medications included in Protocol I or Protocol II will be taken orally for 14 consecutive days. After Protocol II is completed, the remaining patients with persisting infection will be treated by gastroenterologist according clinical practice guidelines. 2. University Hospital Centre Zagreb (KBC Zagreb), Croatia: 13C-urea breath test (UBT) confirmatory testing will be determined. In case of positive results participants will be treated with bismuth-based quadruple therapy (Protocol I). One month following the treatment a control UBT will be performed in order to confirm eradication. In case of treatment failure participants will be treated with second-line treatment (Protocol II). 3. Beacon Hospital, Ireland: H. pylori serology with high sensitivity will be offered to participants. For participants with positive serology test results, an additional UBT confirmatory testing will be the second step to confirm an active infection. H. pylori positive patients will be treated by bismuth-based quadruple therapy (Protocol I). One month after conclusion of the treatment a control UBT will be used to confirm eradication. Patients with treatment failure will be treated with an additional second protocol (Protocol II) according to local recommendations. 4. University of Latvia, Latvia: participants will be tested for H. pylori infection by UBT. H. pylori positive participants will be offered standard triple therapy for 14 days as the first-line therapy: Antibiotic 1 - Amoxicillin 2 x 1000 mg, Antibiotic 2 - Clarithromycin 2 x 500 mg, Proton pump inhibitor - Esomeprazole 2 x 40 mg. At least 30 days after the treatment participants will be retested for H. pylori by UBT to confirm eradication. Participants with treatment failure will be recommended second line treatment - levofloxacin-based: Antibiotic 1 - Levofloxacin 2 x 500 mg, Antibiotic 2 - Amoxicillin 2 x 1000 mg, Proton pump inhibitor - Esomeprazole 2 x 40 mg Or Pylera based: Antibiotic 1 - Metronidazole 4 x 125 mg Antibiotic 2 - Tetracycline 4 x 125 mg Colloidal bismuth - Bismuth Subcitrate Potassium 4 x 140 mg Proton pump inhibitor - Esomeprazole 2 x 40 mg 5. Uniwersytet medyczny we Wrocławiu, Poland: participants will be tested for H. pylori infection by locally validated H. pylori serology test. In case of a positive result the UBT will be performed for confirmation. Positive patients will be treated with bismuth-based quadruple therapy (Protocol I) followed by control UBT in order to confirm eradication. Treatment failure participants will be treated with second line treatment (Protocol II). 6. Iuliu Hațieganu University of Medicine and Pharmacy (UMF), Romania: Locally validated H. pylori serology with high sensitivity will be offered to participants. For participants with positive serology test results, additional UBT confirmatory testing will be the second step to confirm an active infection. H. pylori positive patients with be treated by bismuth-based quadruple therapy (Protocol I). One month after conclusion of the treatment a control UBT will be used to confirm eradication. Patients with treatment failure will be treated with additional second protocol (Protocol II) according to local recommendations. 7. National Institute of Public Health (NIJZ), Slovenia: Locally validated H. pylori serology with high sensitivity will be offered to participants. For participants with positive serology test results, additional UBT confirmatory testing will be the second step to confirm an active infection. H. pylori positive patients with be treated by bismuth-based quadruple therapy (Protocol I). One month after the conclusion of the treatment a control UBT will be used to confirm eradication. Patients with treatment failure will be treated with an additional second protocol (Protocol II) according to local recommendations. The study will be conducted, commencing in 2024 and concluding in 2026. This timeframe has been chosen to allow for participant recruitment, conducting the study and data analysis for a thorough assessment of the feasibility of the proposed screening strategy.

A Study of Vedolizumab With and Without Upadacitinib in Adults With Crohn's Disease

The drug being tested in this study is vedolizumab. Vedolizumab is being tested to treat people with moderately to severely active CD. The study will look at the efficacy and safety of vedolizumab with and without upadacitinib. The study will enroll approximately 396 patients. Participants will be assigned in a 1:1 ratio to one of the two treatment groups in the 12-weeks Induction Phase: - Induction Phase: Vedolizumab + Upadacitinib - Induction Phase: Vedolizumab + Placebo Participants who achieve a Crohn's disease activity index (CDAI) reduction of greater than or equal to (>=)70 points from baseline at Week 12 will enter the main study Maintenance Phase (40 weeks) of the study to receive vedolizumab monotherapy. Participants will be followed for a further 18-week safety follow-up period up to Week 70. This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 70 weeks.

A Study to Determine if BHV-7000 is Effective and Safe in Adults With Refractory Focal Onset Epilepsy

A Study of Efficacy and Safety of Rosnilimab in Subjects with Moderate to Severe Ulcerative Colitis (ROSETTA)

This is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of rosnilimab in subjects with moderate to severe ulcerative colitis (UC).