Neonatal ecmo study of temperature (NEST) - a randomised controlled trial
File(s)
Author(s)
Type
Journal Article
Abstract
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°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°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°C ± 0.2°C. Babies allocated ECMO with cooling will be
managed at 34°C ± 0.2°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°C) will occur at a rate of no more than 0.5°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 ≥ 60; (iii) initial aEEG pattern shown on the cerebral
function monitor, and (iv) primary diagnostic group.
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°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°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°C ± 0.2°C. Babies allocated ECMO with cooling will be
managed at 34°C ± 0.2°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°C) will occur at a rate of no more than 0.5°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 ≥ 60; (iii) initial aEEG pattern shown on the cerebral
function monitor, and (iv) primary diagnostic group.
Date Issued
2010-04-19
Date Acceptance
2010-04-19
Citation
BMC Pediatrics, 2010, 10 (24)
ISSN
1471-2431
Publisher
BioMed Central
Journal / Book Title
BMC Pediatrics
Volume
10
Issue
24
Copyright Statement
© 2010 Field et al. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Sponsor
British Heart Foundation
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000277291100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
SP/04/004 / RM62G0127
Subjects
Science & Technology
Life Sciences & Biomedicine
Pediatrics
PEDIATRICS
EXTRACORPOREAL MEMBRANE-OXYGENATION
HYPOXIC-ISCHEMIC ENCEPHALOPATHY
MILD THERAPEUTIC HYPOTHERMIA
WHOLE-BODY HYPOTHERMIA
PRETERM INFANTS
CARDIOPULMONARY BYPASS
NEUROLOGIC EXAMINATION
BRAIN-INJURY
AGE
BIRTH
Body Temperature
Developmental Disabilities
Extracorporeal Membrane Oxygenation
Female
Follow-Up Studies
Great Britain
Heart Failure
Humans
Hypothermia, Induced
Infant, Newborn
Intelligence
Male
Respiratory Insufficiency
Time Factors
Treatment Outcome
NEST Study Group
Paediatrics And Reproductive Medicine
Publication Status
Published