The BOOST-II UK trial is a research study aimed at improving the way we treat extremely preterm babies. Many preterm babies need extra oxygen to help them to survive. Choosing the right amount of oxygen is difficult because there are risks associated with both higher and lower oxygen levels.
The amount of oxygen a baby is given is guided by measuring how much oxygen is in the blood. This is called the oxygen saturation.
When the BOOST-II UK trial started it was common practice in UK neonatal units to keep the blood oxygen saturation level of preterm babies between 85% and 95%. Within this range we wanted to know whether it makes a difference if babies are treated in the lower part of the range or in the higher part of the range. Since oxygen can affect the development of many organs we aimed to study a number of outcomes. The most important outcome was the health of the babies in the long term – how many babies live or die, and how many of the babies who survive have impairments or disability. We also wanted to know the effect of oxygen on conditions that affect the eyes, lungs and bowels and on the way that babies grow. It will be some time before we know all of this information. It is likely that not all of the outcomes will be affected in the same way. It is because of this that choosing the best oxygen level will not be simple.
Babies in the BOOST-II UK trial were randomly divided into two groups. In one group the aim was to keep the oxygen saturation level as much as possible in the range 85-89% and in the other group in the range 91-95%. It was planned to study 1200 babies in the UK and Ireland. As well as the BOOST-II UK trial there have been very similar trials going on in the United States, Australia, New Zealand and Canada looking at the same question.
As with all large trials, a committee of independent experts monitored the results of the UK trial to see if an important result was found earlier than expected. A special feature of this study is that this data monitoring committee has also communicated with the committees from the other trials around the world so that between them they have more information to look at than would come from a single study. We were informed just before Christmas 2010 that when data from the trials in the UK, Australia, and New Zealand was combined, there was a clear difference between the 2 study groups. Preterm babies who were having their oxygen targeted to keep them in the range 91-95% were surviving more often than preterm babies who were having their oxygen targeted to keep them in the range 85-89%. The difference was so clear that it was extremely unlikely to change if the trial continued to the end. Because of this it was decided that no further babies should be entered into the trial and that babies currently in the trial should not continue in their allocated groups. This was communicated immediately to all of the participating neonatal units.
This initial combined analysis looked only at short-term survival. We needed to collect a lot more information about the babies who have been studied to gain a clear picture of the overall risks and benefits of different oxygen levels. Without this information we were not in a position to recommend a particular target range with confidence.
The full outcomes of the study will not be available until after the follow-up of all the babies in the study has been completed.
In the meantime a second combined analysis has looked at data for a total of 2,448 infants who were recruited to the BOOST II trials (973 in the UK, 1,135 in Australia and 340 in New Zealand), from birth until hospital discharge. This analysis has reviewed the impact that study group allocation had on retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and cranial ultrasound scan abnormality as well as mortality. This analysis confirmed the original findings that preterm babies who were having their oxygen targeted to keep them in the range 91-95% were surviving more often than preterm babies who were having their oxygen targeted to keep them in the range 85-89%. No other significant outcomes were found between the treatment groups.
We are extremely grateful to all of the babies and parents who have participated in this trial. Their involvement will make a big difference to clinical practice and the outcomes of future preterm babies. Participation in trials is vital if we are to continue to improve the treatment options for babies born prematurely.
Clinical Trials Unit:
National Perinatal Epidemiology Unit CTU
University of Oxford
Funded by MRC G0400415 but now managed by the NIHR EME Programme 09/800/25