Clinical trial NCT06757543: A Stepped Wedge Cluster Randomised Trial of Video Versus Direct Laryngoscopy for Intubation of Newborn Infants
Official title: A Stepped Wedge Cluster Randomised Trial of Video Versus Direct Laryngoscopy for Intubation of Newborn Infants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Intubation
Intubation Complications
Infant, Newborn
Infant Respiratory Distress Syndrome
Video Laryngoscopy
Keywords: infant, newborn
video laryngoscopy
intubation
stepped wedge cluster randomised trial
Lead sponsor: University College Dublin
Sponsor class: OTHER
Collaborators: name: National Maternity Hospital, Ireland
name: Leiden University Medical Center
First posted: 2025-01-03
Enrollment: 840
Sex: ALL
Minimum age (years): 0
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Stepped wedge cluster randomised study
Primary purpose: TREATMENT

Brief summary: Many newborn babies have difficulty breathing. When babies need a lot of help, a doctor will intubate them - i.e. put a tube into their windpipe (trachea) - so that they can be given support with a breathing machine. Intubation is a difficult procedure, during which many babies have falls in their blood oxygen levels and heart rate. When doctors intubate babies, they use a device called a laryngoscope to identify the entrance to the windpipe. A standard laryngoscope has a light at its tip. When doctors use this device, they insert it into the baby's mouth and then look directly into the mouth to find the entrance (direct laryngoscopy). Less than half of first attempts to insert a tube are successful using this device. More recently, video laryngoscopes have been developed. These devices also have a camera at the tip and display a magnified view of the entrance to the windpipe on a screen. A study at one hospital showed that the doctors there inserted the tube at the first attempt more often when they used a video laryngoscope instead of a standard laryngoscope. This study was not large enough to see whether fewer babies had low oxygen levels or heart rate during the procedure.

The goal of this clinical trial is to see whether more newborn babies are intubated at the first attempt without falls in their blood oxygen levels or heart rate when the doctors use video laryngoscopy compared to direct laryngoscopy.

Hospitals where doctors routinely intubate babies by looking directly into the mouth will take part in the NEU-VODE study. From the start of the study, the doctors at each hospital will continue with their usual approach to intubation and collect information about intubation attempts. As the study progresses, the doctors at each participating hospital will switch one--by-one to routinely attempting intubation with a video laryngoscope. The date on which they switch will be determined by chance. By the end of the study, each hospital will have had a study period where babies were routinely intubated using direct laryngoscopy and video laryngoscopy.

At the end of the study, the information collected from all the babies intubated during the study will be compared to see if more babies were successfully intubated at the first attempt without falls in their blood oxygen levels or heart rate in the video laryngoscopy group.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* Infants of any gestational age in whom endotracheal intubation is attempted can be included in this study once there is parental consent to the use their infant's data.

Exclusion Criteria:

* Infants will be excluded if parents do not consent for their infants' data to be used.

Primary outcomes:
measure: Successful intubation at the first attempt without physiologic instability
timeFrame: At 5 minutes from the start of the intubation attempt
Secondary outcomes:
measure: Successful intubation at the first attempt
timeFrame: At 5 minutes from the start of the intubation attempt
measure: Physiologic instability during the first intubation attempt
timeFrame: At 5 minutes from the start of the intubation attempt
measure: Lowest SpO2 (%) measured with pulse oximetry during the procedure
timeFrame: At 5 minutes from the start of the intubation attempt
measure: Lowest heart rate (HR) during the procedure
timeFrame: At 5 minutes from the start of the intubation attempt
measure: Number of intubation attempts taken to intubate successfully
timeFrame: At 30 minutes from the start of the intubation attempt
measure: Total laryngoscopy time to successful intubation
timeFrame: At 30 minutes from the start of the intubation attempt
measure: Number of participants successful intubated with assigned device
timeFrame: At 30 minutes from the start of the intubation attempt
measure: Number of participants reported by clinicians to have oral trauma within 1 hour of the intubation attempt
timeFrame: At 1 hour from the start of the intubation attempt
measure: Number of participants given adrenaline (IV or via ETT) within an hour of the intubation attempt
timeFrame: At 1 hour from the start of the intubation attempt
measure: Number of participants given chest compressions within one hour of the intubation attempt
timeFrame: At 1 hour from the start of the intubation attempt
Other outcomes:
Locations:
city: Rijeka
country: Croatia
facility: Clinical Hospital Centre
city: Zagreb
country: Croatia
facility: Clinical Hospital "Holy Spirit"
city: Brno
country: Czech Republic
facility: University Hospital Brno
city: Prague
country: Czech Republic
facility: General University Hospital
city: Prague
country: Czech Republic
facility: Institute for Mother and Child Care
city: Thessaloniki
country: Greece
facility: Aristotle University of Thessaloniki
city: Budapest
country: Hungary
facility: Second Semmelweiss University
city: Padova
country: Italy
facility: University of Padova
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Gdańsk
country: Poland
facility: Medical University of Gdańsk
city: Katowice
country: Poland
facility: Medical University of Silesia
city: Poznań
country: Poland
facility: Poznań University of Medical Sciences
city: Rzeszów
country: Poland
facility: Provincial Hospital No. 2
city: Wrocław
country: Poland
facility: Wrocław Medical University
city: Sibiu
country: Romania
facility: Clinical County Emergency Hospital
city: Tărgu Mures
country: Romania
facility: George Emil Palade University
city: Valencia
country: Spain
facility: University and Polytechnic Hospital La Fe
city: Chernivtsi
country: Ukraine
facility: Bukovinian State Medical University
Study officials:
References:
citation: Geraghty LE, Dunne EA, Ni Chathasaigh CM, Vellinga A, Adams NC, O'Currain EM, McCarthy LK, O'Donnell CPF. Video versus Direct Laryngoscopy for Urgent Intubation of Newborn Infants. N Engl J Med. 2024 May 30;390(20):1885-1894. doi: 10.1056/NEJMoa2402785. Epub 2024 May 5.
citation: Sawyer T, Foglia EE, Ades A, Moussa A, Napolitano N, Glass K, Johnston L, Jung P, Singh N, Quek BH, Barry J, Zenge J, DeMeo SD, Brei B, Krick J, Kim JH, Nadkarni V, Nishisaki A; National Emergency Airway Registry for Neonates (NEAR4NEOS) investigators. Incidence, impact and indicators of difficult intubations in the neonatal intensive care unit: a report from the National Emergency Airway Registry for Neonates. Arch Dis Child Fetal Neonatal Ed. 2019 Sep;104(5):F461-F466. doi: 10.1136/archdischild-2018-316336. Epub 2019 Feb 22.
citation: Singh N, Sawyer T, Johnston LC, Herrick HM, Moussa A, Zenge J, Jung P, DeMeo S, Glass K, Howlett A, Shults J, Barry J, Brei BK, Kim JH, Quek BH, Tingay D, Mehrem AA, Napolitano N, Nishisaki A, Foglia EE; National Emergency Airway Registry for Neonates (NEAR4NEOS). Impact of multiple intubation attempts on adverse tracheal intubation associated events in neonates: a report from the NEAR4NEOS. J Perinatol. 2022 Sep;42(9):1221-1227. doi: 10.1038/s41372-022-01484-5. Epub 2022 Aug 18.
citation: Foglia EE, Ades A, Sawyer T, Glass KM, Singh N, Jung P, Quek BH, Johnston LC, Barry J, Zenge J, Moussa A, Kim JH, DeMeo SD, Napolitano N, Nadkarni V, Nishisaki A; NEAR4NEOS Investigators. Neonatal Intubation Practice and Outcomes: An International Registry Study. Pediatrics. 2019 Jan;143(1):e20180902. doi: 10.1542/peds.2018-0902. Epub 2018 Dec 11.
citation: American Academy of Pediatrics/American Heart Association. Textbook of Neonatal Resuscitation (8th ed, June 2021), editors Weiner GM, Zaichkin J. AAP, Elk Grove, IL USA.