BOOST-II trials


Higher oxygen saturation levels for extremely preterm infants improve disability-free survival in the BOOST-II trials

The risk of death or disability at the age of two years among infants born before 28 weeks' gestation was 5% higher if they had been allocated a lower targeted oxygen saturation (range 85-89 per cent) than a higher targeted oxygen saturation (range 91-95 per cent), in the results of the BOOST-II study published in the New England Journal of Medicine

The BOOST-II Australia (conducted by CTC) and BOOST-II United Kingdom groups combined the results of their two large multicentre trials involving 2108 infants, 1135 in Australia and 973 in the UK. Their work has provided neonatal specialists and hospitals with new clinical evidence of the safer level of blood oxygen to aim for. The results confirm similar findings from a trial in North America, which concluded that targeting oxygen saturation below 90 per cent in extremely preterm infants was associated with a higher risk of death, but not of disability.

Before these findings, neonatologists had targeted oxygen saturation across a wider range, between 85 per cent and 95 per cent. The decision of how much oxygen to give has been a difficult one, because too much and too little can both cause later disability. Now the precision of the target has narrowed considerably.

In the combined analysis of the Australian and UK trial, 48.1% of the infants in the lower-target group and 43.1% in the higher-target group had died or had a disability diagnosed by the age of 2 years.

During the trials, there was a correction to the algorithm that provided data from the oxygen meters. In an extra analysis of data from only the revised oximeters in both trials, the rates of death were 24.5% in the lower-target group and 16.9% in the higher-target group. This was a statistically significant difference.

Professor William Tarnow-Mordi, principal investigator of the Australian study says: 'We now have clearer evidence that the higher concentration of oxygen is superior, increasing survival without an associated increase in disability. If confirmed when combined with the results of three similar trials in the US, Canada and New Zealand, it will help prevent a great many deaths worldwide every year'.

Professor Tarnow-Mordi is professor of neonatal medicine at the CTC. He is a champion of trials to improve the treatment and prospects of newborn babies. He adds: 'Randomised trials like these are the best way to determine which treatments provide the best outcomes.  More trials of other treatments for premature babies are urgently needed to improve their quality of survival. With innovative investment in clinical trial networks and point of care data capture, trials like these could finish much faster, at a fraction of the cost'.  

The principal investigator of the UK BOOST-II study is Professor Ben Stenson. He adds 'The success of trials like these depends on hundreds of people. Thanks to the participation and support of parents and health professionals worldwide, the outlook for very preterm babies has never been better - and is still improving.'

BOOST-II was funded by the National Health and Medical Research Council in Australia and the Medical Research Council in the UK. 

10 February 2016

 

Background 

  • Air contains 21% oxygen. 
  • When we breathe air, this oxygen enters our bloodstream through our lungs. 
  • Most of the oxygen in our blood is carried by a molecule in the red blood cells called haemoglobin.  
  • When a healthy person breathes air (21% oxygen) the haemoglobin in their arteries carries 95-100% of its maximum possible volume of oxygen.  i.e. the arterial haemoglobin is 95-100% saturated with oxygen. 
  • If the lungs aren't working well, the oxygen saturation in arterial blood falls below 90%.  
  • To compensate, patients with sick lungs are given a higher concentration of oxygen to breathe, 22-100%. 
  • Doctors wrap a probe around the wrist or ankle of a baby which shines a bright light through the artery. This probe is attached to a machine called a pulse oximeters, which measures the saturation of the haemoglobin in the arterial blood. 
  • The higher the concentration of oxygen the baby breathes, the greater the arterial oxygen saturation. 
  • However, if babies are given too much oxygen to breathe for prolonged periods, their oxygen saturation will be close to 100% for long periods, which is associated with the risk of eye damage (retinopathy). 
  • In 2005, when these studies were set up, neonatal paediatricians aimed to give enough oxygen to babies to breathe to keep their haemoglobin saturation at 85-95%.