Study protocol for the HiLo-Trial published
Oxygen is a vital element in the care of preterm infants and has been given more often than any other drug over the past 80 years. Despite this, we know very little about how much or how little oxygen is safe particularly at birth. Preterm birth, or birth before 37 weeks’ gestation, is occurring in 8% of pregnancies in Canada. Preterm birth is associated with many health complications, particularly when the birth happens before 29 weeks’ gestation. At this gestational age, the lungs are not fully developed and it is not uncommon for infants to have problems breathing at the time of birth. One complication that can arise is when an infant stops breathing and needs to be resuscitated. When preterm babies need to be resuscitated doctors must take special care because of the immaturity of the brain and lungs. Oxygen is used to resuscitate babies who need it, but unfortunately there is disagreement about the best oxygen concentration to use. Oxygen concentration is important because both too much and too little oxygen can cause brain injury. In the HiLo-trial we compare the effects of resuscitating babies less than 29 weeks’ gestational age with either a low oxygen (30%) concentration or a high oxygen (60%) concentration. The oxygen concentrations have been selected using the best available knowledge at the time of the start of the trial. The trial design is a cluster cross over design, in which each sites recruits a certain number of infants in each arm. Once the target number in one arm has been reached, the site is changing over to the other arm. Once both targets (which are equal numbers) are recruited, the site is closed for recruitment. Thank you to everyone involved and being part of the HiLo-journey and thanks to all the parents who have consented for their babies to be part of this trial.
We just published the Study protocol for the HiLo-Trial in Trials:
check out the Abstract below:
Background: Immediately after birth the oxygen saturation is between 30-50%, which then increases to 85%-95% within the first 10 minutes. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (<0.3), up to moderate concentrations (0.3-0.65). This leaves clinicians in a challenging position and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence.
Methods: An international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 to 286/7 weeks’ gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months’ and then cross over to the other concentration for up to 12 months’. The intervention will be initial FiO2 of 0.6 and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a Type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35% to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18-24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity).
Discussion: The use of supplementary oxygen may be crucial, but also potentially detrimental to preterm infants at birth. The HiLo-trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18-24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice.
Trial registration
The trial was registeredon January 31, 2019atClinicalTrials.gov with the Identifier: NCT03825835.
