Randomized Phase III Clinical Trial Assessing a Supraglottic Device Versus Face-mask Ventilation in Neonatal Resuscitation in Africa

Every year about 1 million newborns die globally due to insufficient oxygen supply during birth and shortly after. Efficient ventilation is the cornerstone of initial respiratory support to newborns. A laryngeal mask airway (LMA), i.e. an airway tube that is inserted through the baby's mouth down to larynx, and once deployed forms an airtight seal on top the glottis allowing a secure airway to be managed by the health care provider. The "i-gel" is a new generation of LMA that permits even novice users to establish an open airway. Our previous pilot study concluded that LMA was safe to use even for midwives. We aimed to investigate whether the use of a cuffless laryngeal mask airway (LMA) compared to FM during neonatal resuscitation could reduce mortality and morbidity in asphyxiated neonates. In this phase III open-label superiority randomized controlled trial in mainly severely depressed neonates in Uganda (median 5-minute Apgar; 5 (interquartile range 4-6)), 563 non-breathing neonates (gestational age over 34 weeks and/or expected birth weight above 2000 g) were assigned to receive positive pressure ventilation (PPV) performed by midwives using LMA, and 591 were assigned to receive PPV using FM (control group). The primary outcome was a composite of 7-day mortality and hypoxic-ischemic encephalopathy (HIE), Thompson score 11 or higher. Safety of midwives´ LMA use was assessed. The primary outcome occurred in 154 (27.4%) neonates in the LMA arm and 144 (24.4%) in the control arm (risk ratio 1.16; 95% confidence interval 0.90 to 1.51; P=0.26). The follow-up rate was 99.2%. Four short-term adverse events occurred, equally distributed between arms. In asphyxiated neonates, LMA was not superior to FM in reducing early neonatal mortality and moderate/severe morbidity. However, the LMA was safe in the hands of midwives. Two PhD candidates will be defending their theses based on this trial.

- The NeoSupra trial successfully completed with 1154 inclusions - 2 PhDs successfully completed (1 submitted, 1 to be submitted later this year) - A large amount of knowledge on neonatal resuscitation that will contribute to further development in this field

Perinatal mortality remains high in Sub-Saharan Africa. The estimated global number of annual deaths due to birth asphyxia is 1 million and the burden of neurological disability in survivors is high. The majority (98%) of these deaths occur in low-resource settings were midwifes are providing initial respiratory support to newborns. Efficient ventilation is the cornerstone of neonatal resuscitation. Ambitious programs focus on training midwifes to improve ventilation skills using conventional face masks (FM), i.e. put over the mouth and nose of the baby. However, a number of studies show that even experienced health providers using FM may deliver inadequate pressure and volume to the lungs of a newborn at the detriment of the infant. A supraglottic device (SD), i.e. an airway tube that is inserted through the baby's mouth down to larynx, and once deployed forms an airtight seal on top the glottis allowing a secure airway to be managed by the health care provider. The I-gel is a new generation of SD that permits even novice users to establish a patent airway. Our phase II trial concluded that resuscitation with I-gel had no adverse events and could safely be task-shifted to midwives. The Neonatal Supraglottic Device Trial is a multi-center facility-based intervention in Uganda and Mozambique. Midwives at the labour ward will undergo a resuscitation refresher course, including a module on SD use. Asphyxiated newborns will be randomized to ventilation with FM or SD and resuscitation will be monitored by closed-circuit video cameras. A research assistant will secure real-time data collection. The primary outcome is death or hospitalization within 7 days of life of the infant. This trial builds on established partnerships and earlier trials in newborn resuscitation by the research group. The study may become a game changer on a global scale by providing evidence for an innovative change in resuscitation practices for improved perinatal health.