Virovitica- Slatina, Croatia

MEN1703 (SEL24) to Treat Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma (JASPIS-01)

The study consists of 3 parts, to investigate MEN1703 (Dapolsertib hydrochloride) in combination with glofitamab in patients who are naïve to treatment with an anti-CD3xCD20 bispecific antibody (group 1) or MEN1703 alone in patients who have exhausted all standard treatment options (group 2). Part 1 (safety run-in) and Part 2 (enrichment): patients who are naïve to treatment with an anti-CD3xCD20 bispecific antibody (group 1) will receive either 150 mg or 125 mg of MEN1703 along with glofitamab. Patients who have exhausted all standard treatment options (group 2) will receive 125 mg of MEN1703 as a single-agent. Part 3 (optional randomized comparison): Patients who are naïve to treatment with an anti-CD3xCD20 bispecific antibody therapy will be randomized to receive either MEN1703 (Dapolsertib hydrochloride) at a dose selected from part 2 in combination with glofitamab or glofitamab alone.

A Clinical Study to Evaluate DNTH103 in Adults with Multifocal Motor Neuropathy

A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC in Adults With Ocular Myasthenia Gravis

A Trial Investigating Lu AG22515 in Adult Participants With Moderate-to-Severe Thyroid Eye Disease

A Study to Assess the Efficacy and Safety of Efgartigimod IV in Adult Participants With Primary Immune Thrombocytopenia

A Study on the Immune Response, Safety and the Occurrence of Respiratory Syncytial Virus (RSV)-Associated Respiratory Tract Illness After Administration of RSV OA Vaccine in Adults 60 Years and Older

A Phase 3, Placebo-controlled, Double-blind Study Assessing Rocatinlimab in Prurigo Nodularis

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

Use of Epoetin Alfa and Iron Derisomaltose in Treatment of Anemia in Patients With Sepsis or Septic Shock: a Randomized Controlled Trial

Project Description: Project Title: The use of epoetin alfa and iron derisomaltose in treating anemia in patients with sepsis or septic shock in the ICU: a randomized controlled clinical trial. Project Acronym: EpoAid Theoretical Background and Rationale: Up to 66% of patients have anemia at admission to the intensive care unit. Additionally, many patients develop anemia during hospitalization in the intensive care unit due to illness and iatrogenic blood loss for laboratory diagnostics. After 72 hours 95% of intensive care unit patients are anemic. Anemia increases the risk of tissue oxygen deficiency, which is particularly important in sepsis or septic shock patients who may have peripheral perfusion disorders due to infection. Anemia should be treated causally because red blood cell transfusions can lead to adverse effects, including immunomodulation leading to innate immunity suppression, which is particularly significant in critically ill sepsis or septic shock patients. Anemia caused by sepsis is known as inflammatory anemia (AI). Sepsis patients often have mixed anemia, combining features of AI and iron deficiency anemia (IDA) - AI+IDA. Currently available treatments for mixed anemia include erythropoiesis-stimulating agents (ESA) and intravenous iron supplements (e.g., iron derisomaltose). Manufacturers of intravenous iron products contraindicate their use in infections since intravenous iron could theoretically exacerbate infections by stimulating pathogen growth. However, there is no conclusive data on this. Considering that stored red blood cells are also a source of iron that pathogens can use, it seems that fractional doses of intravenous iron could benefit sepsis patients with diagnosed iron deficiency. Additionally, ESA administration could cause functional iron deficiency, where small doses of intravenous iron might also be beneficial. Attempts to use ESA and intravenous iron in the general ICU population have yielded inconclusive results due to methodological errors. In the IRONMAN study comparing iron carboxymaltose with placebo, no difference in transfusion rates (primary endpoint) was found, but higher Hb levels were observed at hospital discharge in the intervention group (107 vs. 100 g/L). This trial had some methodological flaws: intravenous iron was administered regardless of anemia etiology, red blood cell transfusion decisions were made by clinicians - there was no transfusion algorithm, and the average hospital stay was 11 days - maximal effect of intravenous iron is seen after 3-4 weeks, at least 2 weeks. Iron deficiency diagnostics in sepsis patients must rely on parameters independent of the systemic inflammatory response since standard iron metabolism parameters (ferritin, transferrin saturation) are not useful here. Severe sepsis was an exclusion criterion in the IRONMAN study. Given the limitations of previous studies and the lack of research on the use of intravenous iron in sepsis patients, it is warranted to conduct a study evaluating the effect of epoetin alfa ± iron derisomaltose on Hb levels in sepsis or septic shock patients. Hypothesis and Research Aim: Causal treatment of anemia in sepsis or septic shock patients may lead to increased Hb levels and reduced transfusion rates, potentially improving patient outcomes. This study aims to evaluate the effect of epoetin alfa ± iron derisomaltose on one primary and several secondary outcomes. Materials and Methods: A randomized controlled clinical trial is planned. Blinding will be single due to the color (rusty) of the intervention drug (iron derisomaltose) and problems with complete blinding of the intervention. Randomization will be done using a computer generator of randomized numbers using block of 4. Two hundred patients will be recruited (100 in the experimental group, 100 in the control group). If a study subject starts bleeding or requires surgery (affects Hb levels and transfusion necessity - primary endpoints), the time until this event will be evaluated. Data collected: demographics (gender, age), infection site, length of stay (ICU, hospital), mortality (ICU, hospital, 30 days, 90 days). Blood loss for laboratory diagnostics will be monitored (calculation based on laboratory parameters ordered and test tube used). Pharmacological venous thromboembolism prophylaxis will be used in the experimental and contorol groups: enoxaparin 40 mg x 1 sc in patients with creatinine clearance ≥30 mL/min or dalteparin 5000 IU x 1 sc in patients with creatinine clearance <30 mL/min, and a red blood cell transfusion decision algorithm will be employed. Experimental group: 1. epoetin alfa (Binocrit, Sandoz, Poland) given intravenously when Hb <120 g/L, dosed by a study subject weight: - 2000 IU (<60 kg) - 3000 IU (60-79 kg) - 4000 IU (80-99 kg) - 5000 IU (>100 kg) administered on days 1, 3, 5, 8, 10, 12 2. iron derisomaltose (Monover, Pharmacosmos, Denmark) given intravenously at a dose of 0.2g when Hb <120 g/L and RET-He <29.3 pg, administered on days 1, 3, 5, 8, 10, 12 3. red blood cell transfusion decision based on a proprietary decision algorithm. Binocrit will be stored at 2-8 °C. Before use, the drug will be stored at room temperature for 15 minutes. The drug is packaged in prefilled syringes; it will be mixed with 0.9% sodium chloride to a volume of 20 mL, then injected intravenously as a bolus, followed by a 20 mL 0.9% NaCl sodium chloride bolus to ensure immediate drug entry into the bloodstream. It is crucial to administer the entire dose without loss, as it is the primary intervention drug in this study. Monover is provided in 0.1g ampoules. The drug will be administered at a fixed dose of 0.2g when RET-HE <29.3 pg on the scheduled administration day. The drug will be diluted with 0.9% NaCl to a volume of 50mL and administered in a brown 50mL syringe using an infusion pump at a rate of 60mL/h. Control Group: red blood cell transfusion decision based on a proprietary decision algorithm. Monitored parameters: - initial lab parameters (extended): interleukin-6, procalcitonin, C-reactive protein, creatinine, ammonia, blood urea nitrogen, aspartate aminotransferase (AspAT), alanine aminotransferase, total bilirubin, complete blood count (CBC), reticulocytes (RET), ferritin, iron, transferrin. - serial measurements: Hb and hemoglobin equivalent in reticulocytes (RET-He) on the day of epoetin alfa ± iron derisomaltose administration. Timeline: November 2024 - December 2026 Feasibility: given the number of ICU hospitalizations (approximately 400 per year) and the prevalence of sepsis/septic shock, it will be possible to enroll about 100 patients per year.