Neonatal ECMO Study of Temperature (NEST)--a randomised controlled trial.
Field DJ., Firmin R., Azzopardi DV., Cowan F., Juszczak E., Brocklehurst P., NEST Study Group None.
BACKGROUND: Existing evidence indicates that once mature neonates with severe cardio-respiratory failure become eligible for Extra Corporeal Membrane Oxygenation (ECMO) their chances of intact survival are doubled if they actually receive ECMO. However, significant numbers survive with disability. NEST is a multi-centre randomised controlled trial designed to test whether, in neonates requiring ECMO, cooling to 34 degrees C for the first 48 to 72 hours of their ECMO course leads to improved later health status. Infants allocated to the control group will receive ECMO at 37 degrees C throughout their course, which is currently standard practice around the world. Health status of both groups will be assessed formally at 2 years corrected age. METHODS/DESIGN: All infants recruited to the study will be cared for in one of the four United Kingdom (UK) ECMO centres. Babies who are thought to be eligible will be assessed by the treating clinician who will confirm eligibility, ensure that consent has been obtained and then randomise the baby using a web based system, based at the National Perinatal Epidemiology Unit (NPEU) Clinical Trials Unit. Trial registration.Babies allocated ECMO without cooling will receive ECMO at 37 degrees C +/- 0.2 degrees C. Babies allocated ECMO with cooling will be managed at 34 degrees C +/- 0.2 degrees C for up to 72 hours from the start of their ECMO run. The minimum duration of cooling will be 48 hours. Rewarming (to 37 degrees C) will occur at a rate of no more than 0.5 degrees C per hour. All other aspects of ECMO management will be identical. PRIMARY OUTCOME: Cognitive score from the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) at age of 2 years (24 - 27 months). DISCUSSION: For the primary analysis, children will be analysed in the groups to which they are assigned, comparing the outcome of all babies allocated to "ECMO with cooling" with all those allocated to "ECMO" alone, regardless of deviation from the protocol or treatment received. For the primary outcome the analysis will compare the mean scores for each group of surviving babies. The rationale for this choice of primary analysis is to give a fair representation of the average ability of assessable children, accepting the limitation that excluding deaths might impose.The consistency of the effect of cooling on the group of babies recruited to the trial will be explored to see whether cooling is of particular help, or not, to specific subgroups of infants, using the statistical test of interaction. Therefore pre-specified subgroup analyses include: (i) whether the ECMO is veno-arterial or veno-venous; (ii) whether the child's oxygenation index at the time of recruitment is <60 or > or = 60; (iii) initial aEEG pattern shown on the cerebral function monitor, and (iv) primary diagnostic group. TRIAL REGISTRATION: Current Controlled Trials ISRCTN72635512.