Seneffe, Belgium

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

Comparison of Clinical Value in the Use of the Fascia Lata and Temporal Muscle Fascia in the Reconstruction of the Dura in the Sellar Region

Study Title: Assessing the Clinical Significance of Using Fascia Lata versus Temporalis Muscle Fascia for Skull Base Reconstruction in Sellar Region Study Objective: The primary objective of this prospective randomized controlled study is to evaluate and compare the effectiveness and safety of using fascia lata and temporal muscle fascia for skull base reconstruction in the sellar region following endoscopic endonasal surgery. The study aims to determine the level of donor site pain using Visual Analogue Scales (VAS) and to identify the optimal reconstruction method with the lowest complication rates. Background: Tumors in the sellar region, such as pituitary adenomas, craniopharyngiomas, meningiomas, and chordomas, present significant surgical challenges due to their location. Advances in endoscopic techniques have improved surgical outcomes for these tumors, but complications, particularly cerebrospinal fluid (CSF) leaks, remain common. Reconstruction of skull base defects is critical to prevent CSF leaks and associated infections. Autologous grafts, including fascia lata and temporal muscle fascia, are commonly used for this purpose. This study seeks to compare these two graft materials in terms of effectiveness, safety, and patient quality of life post-surgery. Study Design: Type: Prospective randomized controlled trial. Enrollment: 68 adult patients. Randomization: Participants will be randomly assigned to one of two groups: Group 1: Skull base reconstruction using fascia lata. Group 2: Skull base reconstruction using temporal muscle fascia. Blinding: Single-blind (patients will not know which type of fascia is used for their reconstruction). Duration: The study will commence in August 2023 and is expected to last for 2-3 years. Inclusion Criteria: Adult patients (18 years and older) undergoing endoscopic endonasal surgery for sellar region tumors. Patients requiring reconstruction of the sellar floor to prevent postoperative CSF leaks. Exclusion Criteria: Pathology at the donor site (trauma, previous surgery). Absence of intraoperative CSF leak. Use of alternative reconstruction materials. Prior radiation therapy to the operative or donor site. Interventions: Group 1 (Fascia Lata): Grafts harvested from the thigh. Group 2 (Temporal Fascia): Grafts harvested from the temporal muscle area. All surgeries will be performed by a standardized surgical team comprising a neurosurgeon and an otolaryngologist. The techniques for incision, hemostasis, and reconstruction will be consistent across all procedures. Outcome Measures: Primary Outcome: Donor site pain assessed using Visual Analogue Scales (VAS) at the following time points: preoperative, postoperative days 1, 2, and 3, and at 1 and 3 months post-surgery. Secondary Outcomes: Incidence of postoperative complications such as meningitis, CSF leak, donor site infection, wound dehiscence, seroma, facial nerve palsy, hypoesthesia of the donor site skin, and diabetes insipidus (temporary or permanent). Quality of life measured using the EQ-5D-5L questionnaire before surgery and at 1 and 3 months postoperatively. Duration of surgical procedures. Length of hospital stay. Statistical Analysis: Power Analysis: A sample size of 34 participants per group is required to achieve 80% power to detect a 30% difference in the incidence of mild versus moderate/severe pain (VAS > 3.5), with a significance level of α = 0.05. Power analysis was conducted using MedCalc® Statistical Software version 22.003. Data Analysis: Normality of data distribution will be tested using histograms and the Kolmogorov-Smirnov test. Continuous variables will be presented as mean (95% confidence interval) or median (interquartile range), depending on distribution. Categorical variables will be presented as absolute frequencies and percentages. Differences in continuous variables between groups will be analyzed using one-way ANOVA with post-hoc tests for parametric data or Kruskal-Wallis test with Dunn's post-hoc test for non-parametric data. Differences in categorical variables will be analyzed using Fisher-Freeman-Halton test for independent samples or McNemar's test for paired samples. A significance level of p < 0.05 will be considered statistically significant. Data analysis will be performed using IBM SPSS Statistics version 29.0.1. Ethical Considerations: The study has been approved by the Ethics Committee of KBC Zagreb. Informed consent will be obtained from all participants prior to their inclusion in the study. Participant privacy will be protected by anonymizing personal data and using unique coded identifiers. Access to anonymized data will be strictly controlled, and any de-anonymization will occur only under the supervision of the Ethics Committee. Funding: The study is funded through clinical research funds dedicated to scientific investigations at KBC Zagreb. Expected Contributions: The study aims to provide empirical evidence on the comparative effectiveness and safety of fascia lata versus temporal muscle fascia for skull base reconstruction. Results will guide clinical decision-making, potentially reducing perioperative morbidity, enhancing patient recovery, and improving quality of life post-surgery.

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 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

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.

Quizartinib or Placebo Plus Chemotherapy in Newly Diagnosed Patients With FLT3-ITD Negative AML

This is a clinical trial to compare the effect of quizartinib versus placebo (administered with standard induction and consolidation chemotherapy, then administered as maintenance therapy for up to 36 cycles) on the primary endpoint of overall survival (OS) in adult patients with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) negative acute myeloid leukemia (AML). Participants will be tested for FLT3-ITD mutation status in a central laboratory using a validated assay.

A Study of Belrestotug Plus Dostarlimab Compared With Placebo Plus Pembrolizumab in Previously Untreated Participants With Programmed Death Ligand 1 (PD-L1) High Non-small-cell Lung Cancer (NSCLC)

Advancing Knowledge in Ischemic Stroke Patients on Oral Anticoagulants

Development and Validation of a New Paediatric Inflammatory Bowel Disease NUTrition Risk Score (PIBD-NUTS)

SELECT-LIFE: A Research Study Looking at Long-term Effects of Semaglutide in People Who Took Part in the SELECT Cardiovascular Outcomes Trial