Ranipet, India

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.

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.

Advancing Knowledge in Ischemic Stroke Patients on Oral Anticoagulants

High - Flow Nasal Cannula Versus Conventional Nasal Cannula During Endobronchial Ultrasound Procedure

Introduction 1. EBUS - bronchoscopy From a physiological point of view bronchoscopy is an introduction of a foreign body into the airway. Response mechanisms include laryngospasm, bronchospasm, cough, increased secretion of bronchial mucus and reduced depth of breathing. Sympathetic response with increased heart rate and blood pressure is common even before the procedure, while the patient is being prepared on the examination table. The bronchoscope occupies 10 to 15% of the cross-sectional area in the major airways and increases air flow resistance. Suction applied during the procedure causes air stealing through the working channel of the bronchoscope which reduces end inspiratory and expiratory volumes leading to alveolar de-recruitment with increased intrapulmonary shunting consequently. EBUS bronchoscopy is associated with prolonged procedure time, increased airway contact, a thicker instrument, and multiple needle punctures through the tracheal and/or bronchial wall. All these factors cause additional stress to the patient and require additional local anesthesia and deeper level of sedation. 2. Sedation Although topical anesthesia of the upper airways, vocal cords, trachea, and bronchi enables a tolerable bronchoscopic procedure, a moderate level of sedation during bronchoscopy is currently the golden standard. Use of sedation facilitates the passage through the vocal cords, inhibits airway protective reflexes and increases patient safety (2,3). In combination with physiological responses to bronchoscopy which increase oxygen demand, sedatives used during bronchoscopy reduce respiratory drive and further compromise patients, especially those with chronic diseases. When it occurs, hypoxemia can induce periprocedural arrythmias and ischemia therefore should be generally avoided and, if encountered, must be reverted quickly (4). An oxygenation strategy with appropriate oxygen supplementation is therefore required during most bronchoscopic procedures. 3. Oxygen supplementation Low flow oxygen up to 6 liters per minute applied through a nasal catheter is the most often used method for oxygen supplementation during flexible bronchoscopy. Inspired oxygen fraction (FiO2) can reach up to 45% but cannot be reliably predicted and may not be enough in all cases. High flow nasal cannula (HFNC), a device first introduced in neonates and pediatric care, is currently used in a wide range of indications in adult respiratory and critical care medicine (5-7). It is a relatively new method in bronchoscopy with several notable theoretical advantages over low flow oxygen via conventional nasal cannula (CNC): - High flow up to 60 liters per minute ensures a more stable FiO2 and better matches the increased patient's inspiratory flow - High flow generates a small positive expiratory airway pressure (up to 5 cm H2O) which could stabilize the upper airways during sedation and have a beneficial effect in the lower airways - High flow reduces dead space in the upper airways and increases alveolar ventilation. CPAP and NIV can provide similar beneficial effects, but their use is challenging because they require a close-fitting facial mask which limits the use of a bronchoscope, aspiration of secretions from the upper airways, pharynx, or oral cavity and expectoration of sputum. 4. Previous studies on HFNC A recent meta-analysis which included six randomized controlled trials found that patients who underwent bronchoscopy with the use of HFNC experienced less hypoxemic events and desaturations, had fewer procedural interruptions and pneumothorax compared to patients supplemented with CNC (10). The three studies which evaluated HFNC during EBUS all showed that HFNC is more effective than CNC during the procedure and that HFNC can be considered an alternative to CNC. However, the studies had several important limitations such as a low number of patients included with a historical control (Takakuwa O et al), a large difference in FiO2 between trial groups (2L/min in the CNC vs. 100% FiO2 and 70L/min flow rate in the HFNC group) (Irfan et al) and lack of assessment of CO2 levels during the procedure (Ulcar et al). Nevertheless, conclusions suggested that HFNC is sufficiently safe and provides adequate oxygenation for most of bronchoscopy examinations including EBUS (8,9). 5. Study questions Our hypothesis is that HFNC provides better control over hypoxemia during EBUS-TBNA procedure than CNC. The primary outcome of the study is therefore proportion of patients with successfully controlled hypoxemia during EBUS TBNA in each arm. Secondary outcomes are incidence of complications in each arm (number of hypoxemic events, mean lowest oxygen saturation during procedure, average saturation, drop in saturation, pulse rate, blood pressure, incidence of arrhythmia), number of patients who experienced mild, moderate, or severe hypoxemia, number of patients who required escalation of the support and which support is effective, what are risk factors for desaturation. Methods 1. Study design and study population The study is designed as multicenter randomized controlled prospective trial. Study will enroll patients who need EBUS -TBNA procedure with sampling of mediastinal lymph nodes for diagnosis and/or staging. Patients will be recruited from four university hospitals in Slovenia, Croatia, Portugal and Greece. Study was approved by The National Medical Ethics Committee of the Republic of Slovenia and registered as 0120-294/2023/3. 2. Recruitment, consensus, and randomization Bronchoscopy coordinator will screen the scheduled patients and notify study investigator about eligible patients. Study investigator will explain the study to eligible patients and obtain informed consents. Inclusion and exclusion criteria will be checked on the day of examination from the data routinely obtained before procedure, including laboratory data. Patients will be randomized in bronchoscopy suite according to allocation group written in sequentially numbered, sealed and opaque envelopes. Envelopes will be prepared by independent statistician on the basis of block randomization with the block size of 4. 3. Bronchoscopy and sedation Topical anesthesia with lidocaine will be provided routinely before insertion of the bronchoscope. Patients will be sedated by bedside anesthesiologist by combination of midazolam, fentanyl and propofol. The depth of sedation will be assessed using Modified Observer's Assessment of Alertness / Sedation scale (MOAA/S). The level of sedation will be maintained between 1 and 2 throughout the procedure. Patients will be monitored by BIS monitor for further analysis and comparison. The standard group of patients will receive oxygen through double-prong nasal cannula with the oxygen flow set to 6 liters per minute, which corresponds to FiO2 45%. The HFNC group will receive mixture of oxygen and air at FiO2 45% with initial flow of 60 liters per minute pre-warmed to 37 degrees of Celsius. Nasal cannula will be chosen according to the patient's face size. Before procedure, patients from both groups will be tested with HFNC with the flow of 60 l/min if they are able tolerate it. EBUS bronchoscope will be inserted through the oral bite block by experienced bronchoscopist and the whole procedure will be conducted according to ERS recommendations. After systematical evaluation of mediastinal and hilar lymph nodes, EBUS TBNA's will be performed according to the individual procedure plan. Patients will be monitored by continuous pulse oximetry, periodical blood pressure measurements, ECG and BIS. 4. Hypoxemia escalation protocol, complications, and termination criteria Oxygen will be delivered to the patient according to the allocation group (6l/min O2 CNC or 45% FiO2 60 l/min HFNC). If desaturation occurs, defined as SpO2<90% for more than 10s the patients will be approached according to the escalation protocol (Figure 1): 1. jaw thrust maneuver 2. patients in CNC group will be switched to 45% FiO2 60 l/min HFNC 3. patients with 45% FiO2 60 l/min HFNC will be switched to 100% FiO2 4. patients with HFNC failure will be switched to advanced respiratory support (balloon ventilation, laryngeal mask, intubation, reversal of sedation) In the case of moderate hypoxemia there will be temporal suspension of the bronchoscopy but in the case of severe hypoxemia the termination of the procedure will be considered if there is no immediate improvement after escalation of ventilatory support. Procedure will be terminated also in the case of other severe adverse events as are hemodynamic instability, myocardial ischemia, or pneumothorax. Resuscitation equipment will be prepared on dedicated medical cart inside the bronchoscopy suite. Any patient with adverse event will be monitored until complete recovery (Alderete score 9 or more). Complications, relevant to the decisions and study outcomes are defined as (1): - Desaturation <90% for more than 10s - Moderate desaturation 75%<= SpO2 <90% less than 60s - Severe desaturation <75% or 75%<= SpO2 <90% more than 60s - Tachycardia >100 or +25% - Bradycardia <50 or -25% - Hypertension +25% - Hypotension <90mmHg or -25% 5. Data collection Demographic data of patients (age, gender, height, weight, BMI, STOP-BANG score, ASA score) and laboratory results (lung function testing) relevant for the study will be collected before the procedure. During and after the procedure, there will be continuous (SpO2, pulse rate, ECG) or periodical (blood pressure) monitoring of vital signs and depth of the sedation (BIS, MOAA/S). The starting point of the procedure T0 is defined as the time immediately prior sedatives are given to the patient. T1 is the time point, where bronchoscope is inserted and Tend is the end of the procedure, when bronchoscope is withdrawn. Venous blood for pCO2 analysis will be drawn at T0 (on the procedure table before sedation) and at Tend (withdrawal of the bronchoscope). Timing and duration of desaturation, the lowest SpO2 and all treatment escalations will be recorded as well as other possible complications. 6. Sample size The protocol is designed to show a superiority of HFNC over CNC. According to pulled data in recently published meta-analysis we expect a 12% desaturation rate in the HFNC group and a 34% desaturation rate in CNC group. The sample size should be 112 with a confidence level (alpha) of 95%, power (1-beta) of 80%. With expected drop out of 25% the final number of included participants is set to 150. A web-based application was used for sample size calculation (https://clincalc.com/stats/samplesize.aspx). 7. Statistical analysis Data will be collected in specially designed case report formulars (CRF) and analyzed by GraphPad Prism 9.5. software (Boston, MA). Categorical variables will be presented as percentages and analyzed by chi-square test. Numerical variables will be presented as mean and standard deviation or median and ranges. Distribution will be tested by the Kolmogorov - Smirnov test and further analysis performed by t-test or Mann Whitney test depending on normality of distribution. Two-sided p-value will be regarded as statistically significant if < 0,05. 8. Patient and public involvement Patients and public were not involved in the study design. References: 1. Mason KP, Green SM, Piacevoli Q; International Sedation Task Force. Adverse event reporting tool to standardize the reporting and tracking of adverse events during procedural sedation: a consensus document from the World SIVA International Sedation Task Force. Br J Anaesth. 2012 Jan;108(1):13-20. doi: 10.1093/bja/aer407. PMID: 22157446. 2. Sazak H, Tunç M, Alagöz A, Pehlivanoğ Lu P, Demirci NY, Alıcı İO, et al. Assessment of perianesthesic data in subjects undergoing endobronchial ultrasound-guided transbronchial needle aspiration. Respir Care. 2015;60(4):567-76. 3. Douglas N, Ng I, Nazeem F, Lee K, Mezzavia P, Krieser R, et al. A randomised controlled trial comparing high-flow nasal oxygen with standard management for conscious sedation during bronchoscopy. Anaesthesia. 2018;73(2):169-76. 4. Du Rand IA, Blaikley J, Booton R, Chaudhuri N, Gupta V, Khalid S, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. Thorax. 2013 Aug;68 Suppl 1:i1-44. 5. Sreenan C, Lemke RP, Hudson-Mason A, Osiovich H. High-Flow Nasal Cannulae in the Management of Apnea of Prematurity: A Comparison With Conventional Nasal Continuous Positive Airway Pressure. Pediatrics [Internet]. 2001 May 1;107(5):1081-3. Available from: https://doi.org/10.1542/peds.107.5.1081 6. Roca O, Riera J, Torres F, Masclans JR. High-Flow Oxygen Therapy in Acute Respiratory Failure. Respir Care [Internet]. 2010 Apr 1;55(4):408 LP - 413. Available from: http://rc.rcjournal.com/content/55/4/408.abstract 7. Nishimura M. High-Flow Nasal Cannula Oxygen Therapy Devices. Respir Care [Internet]. 2019 Jun 1;64(6):735 LP - 742. Available from: http://rc.rcjournal.com/content/64/6/735.abstract 8. Takakuwa O, Oguri T, Asano T, Fukuda S, Kanemitsu Y, Uemura T, et al. Prevention of hypoxemia during endobronchial ultrasound-guided transbronchial needle aspiration: Usefulness of high-flow nasal cannula. Respir Investig. 2018;56(5):418-23. 9. Irfan M, Ahmed M, Breen D. Assessment of High Flow Nasal Cannula Oxygenation in Endobronchial Ultrasound Bronchoscopy: A Randomized Controlled Trial. J Bronchol Interv Pulmonol. 2021;28(2):130-7. 10. Su C-L, Chiang L-L, Tam K-W, Chen T-T, Hu M-C (2021) High-flow nasal cannula for reducing hypoxemic events in patients undergoing bronchoscopy: A systematic review and meta- analysis of randomized trials. PLoS ONE 16(12): e0260716. https://doi.org/10.1371/journal. pone.0260716

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

Therapeutic Options for CRAB

The primary goal will be to negativize positive samples (surveillance or diagnostic) after 10 days of therapy. In addition to the control samples with the same name, samples will be taken on the 4th, 7th, and 10th day after starting treatment. The secondary objectives will include 30-day survival, discharge from the ICU, discharge from the hospital, reduction in SOFA score, rate of reinfection, and frequency of complications (deterioration of renal function). Reduction of CRP, PCT, and leukocytes, improvement of the clinical picture, improvement of radiological findings (such as X-ray of the lungs), and reduction of elevated body temperature will also be included. Patients who require treatment in the ICU with a positive sample (surveillance or diagnostic) for A. baumannii, with clinical signs of infection (temperature >38.5, CPR >50, L >10000) (in which no infection can be explained by another cause) will be included. Three groups will be formed: 1. colistin + fosfomycin 2. colistin + ampicilin/sulbactam 3. colistin + eravacyclin The outcomes will include a negative sample, length of stay in the ICU, length of stay in the hospital, and reduction of SOFA score. The hypothesis will be that the combination of fosfomycin with colistin and eravacyclin with colistin will lead to faster negative samples than the combination of ampicillin/sulbactam with colistin in intensive care unit patients diagnosed with carbapenem-resistant A. baumannii. After obtaining approval from the ethics committee of KBC Zagreb, this study will be conducted at the UHC Zagreb, Department of Anesthesiology and ICU. Patients will be randomly divided according to a predetermined randomization table. Upon arrival of a positive microbiological finding on A. baumannii, the Fosfomycin group will receive fosfomycin 8 g every 8 h, together with a colistin bolus of 6 million IJ, followed by 3 million IJ every 8 h. After the first day, the dose will be adjusted according to kidney and liver function. Therapy will be administered for 10 days. Upon arrival of a positive microbiological finding on A. baumannii, the Ampicilin/sulbactam group will receive a bolus dose of ampicillin/sulbactam 2 g + 1 g and a continuous infusion of 8 g + 4 g over 24 h together (maximum daily dose 12 g/day) with a colistin bolus of 6 million IJ, followed by 3 million IJ every 8 h. After the first day, the dose will be adjusted according to kidney and liver function. Therapy will be performed for 10 days. Upon arrival of a positive microbiological finding for A. baumannii, the Eravacyclin group will receive eravacycline at a dose of 1 mg/kg every 12 h for 60 min together with a colistin bolus of 6 million IU, and then 3 million IU every 8 h. After the first day, the dose will be adjusted according to kidney and liver function. Therapy will be administered for 10 days. After the first positive microbiological finding for A. baumannii, the test will be repeated on the 4th, 7th, and 10th days from the start of therapy. The Charlson Comorbidity Index will be calculated for each patient upon inclusion in the study. The SOFA score will be calculated daily for each patient over 10 days. Patient data from a hospital information system will be used in this study. Demographic data, comorbidities, habits (alcohol and cigarettes), Charlson comorbidity index, SOFA score, allergies, and the type of positive sample will be recorded. The Charlson Comorbidity Index will be calculated for each patient upon inclusion in the study. The SOFA score will be calculated daily for each patient over 10 days. Patients will be included in the study after the arrival of a microbiological test positive for A. baumannii. A routine antimicrobial susceptibility test will be performed when the microbiological findings are positive for A. baumannii. The sensitivity of all A. baumannii strains included in the study, regardless of the group to which they belonged (fosfomycin, ampicilin/sulbactam, and eravacyclin), will be determined during the microbiological analysis of all A. baumannii strains included in the study. After the first positive microbiological finding for A. baumannii, the test will be repeated on the 3th, 7th, and 10th days from the start of therapy. For each patient included in the study, inflammatory parameters (leukocytes, CRP, procalcitonin, IL6) and the number of days and discharge from the ICU and hospital as well as 30-day mortality and cause of death, complications (AKI and ALF), and reinfection will be monitored. For a test power of 80% and the use of an independent t-test for the primary objective and a chi-square test for the secondary objective with a statistical significance of 0.05, it will be necessary to include 108 patients, divided into three groups, with 36 subjects per group. The test for power calculation will be conducted using G Power Version 3.1.9.6. The results will be processed using IBM SPSS Statistics v27.

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.

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)

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.