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Real-time continuous glucose monitoring in preterm infants (REACT): an international, open-label, randomised controlled trial

Real-time continuous glucose monitoring in preterm infants (REACT): an international, open-label, randomised controlled trial
Real-time continuous glucose monitoring in preterm infants (REACT): an international, open-label, randomised controlled trial

Background: hyperglycaemia and hypoglycaemia are common in preterm infants and have been associated with increased risk of mortality and morbidity. Interventions to reduce risk associated with these exposures are particularly challenging due to the infrequent measurement of blood glucose concentrations, with the potential of causing more harm instead of improving outcomes for these infants. Continuous glucose monitoring (CGM) is widely used in adults and children with diabetes to improve glucose control, but has not been approved for use in neonates. The REACT trial aimed to evaluate the efficacy and safety of CGM in preterm infants requiring intensive care. 

Methods: this international, open-label, randomised controlled trial was done in 13 neonatal intensive care units in the UK, Spain, and the Netherlands. Infants were included if they were within 24 h of birth, had a birthweight of 1200 g or less, had a gestational age up to 33 weeks plus 6 days, and had parental written informed consent. Infants were randomly assigned (1:1) to real-time CGM or standard care (with masked CGM for comparison) using a central web randomisation system, stratified by recruiting centre and gestational age (<26 or ≥26 weeks). The primary efficacy outcome was the proportion of time sensor glucose concentration was 2·6–10 mmol/L for the first week of life. Safety outcomes related to hypoglycaemia (glucose concentrations <2·6 mmol/L) in the first 7 days of life. All outcomes were assessed on the basis of intention to treat in the full analysis set with available data. The study is registered with the International Standard Randomised Control Trials Registry, ISRCTN12793535. 

Findings: between July 4, 2016, and Jan 27, 2019, 182 infants were enrolled, 180 of whom were randomly assigned (85 to real-time CGM, 95 to standard care). 70 infants in the real-time CGM intervention group and 85 in the standard care group had CGM data and were included in the primary analysis. Compared with infants in the standard care group, infants managed using CGM had more time in the 2·6–10 mmol/L glucose concentration target range (mean proportion of time 84% [SD 22] vs 94% [11]; adjusted mean difference 8·9% [95% CI 3·4–14·4]), equivalent to 13 h (95% CI 5–21). More infants in the standard care group were exposed to at least one episode of sensor glucose concentration of less than 2·6 mmol/L for more than 1 h than those in the intervention group (13 [15%] of 85 vs four [6%] of 70). There were no serious adverse events related to the use of the device or episodes of infection.

 Interpretation: real-time CGM can reduce exposure to prolonged or severe hyperglycaemia and hypoglycaemia. Further studies using CGM are required to determine optimal glucose targets, strategies to obtain them, and the potential effect on long-term health outcomes. Funding: National Institute for Health Research Efficacy and Mechanisms Evaluation Programme.

2352-4650
265-273
Beardsall, Kathryn
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Thomson, Lynn
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Guy, Catherine
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van Weissenbruch, Mirjam M.
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Bond, Simon
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Kim, Sungwook
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Petrou, Stavros
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Pantaleo, Beatrice
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Hovorka, Roman
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Dunger, David
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Molnar, Zoltan
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Barlow, Sheula
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Baugh, Sharon
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Johnson, Kathryn A.
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Uryn, Lindsay
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Spencer, Collette
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Hubbard, Maria
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Somisetty, Sateeshkumar
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Adesiyan, Olaitan
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Kapadia, Jogesh
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Millar, Yvonne
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Gurusamy, Kalyana
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Bibb, Lindsay
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Jones, Kathryn
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Heaver, Richard
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Muthukumar, Priya
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Nichols, Amy
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Johnson, Mark
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Pond, Jenny
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Crowley, Philippa
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Mellish, Christie
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Shah, Divyen D.
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Abraham, Mercy
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Vincent, Presillina
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Anil kumar, Suma
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Iringan, Angelina
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Aninakwa, Barbara
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de Lange, Annemieke
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REACT collaborative
Beardsall, Kathryn
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Thomson, Lynn
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Guy, Catherine
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van Weissenbruch, Mirjam M.
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Bond, Simon
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Allison, Annabel
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Kim, Sungwook
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Petrou, Stavros
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Pantaleo, Beatrice
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Hovorka, Roman
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Hubbard, Maria
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Millar, Yvonne
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Gurusamy, Kalyana
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Bibb, Lindsay
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Jones, Kathryn
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Heaver, Richard
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Muthukumar, Priya
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Nichols, Amy
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Johnson, Mark
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Pond, Jenny
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Crowley, Philippa
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Mellish, Christie
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Vincent, Presillina
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Anil kumar, Suma
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Iringan, Angelina
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Aninakwa, Barbara
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Dalangin-Chalmers, R. A.
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de Lange, Annemieke
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Johnson, Kathryn A. and Jones, Kathryn , REACT collaborative (2021) Real-time continuous glucose monitoring in preterm infants (REACT): an international, open-label, randomised controlled trial. The Lancet Child and Adolescent Health, 5 (4), 265-273. (doi:10.1016/S2352-4642(20)30367-9).

Record type: Article

Abstract

Background: hyperglycaemia and hypoglycaemia are common in preterm infants and have been associated with increased risk of mortality and morbidity. Interventions to reduce risk associated with these exposures are particularly challenging due to the infrequent measurement of blood glucose concentrations, with the potential of causing more harm instead of improving outcomes for these infants. Continuous glucose monitoring (CGM) is widely used in adults and children with diabetes to improve glucose control, but has not been approved for use in neonates. The REACT trial aimed to evaluate the efficacy and safety of CGM in preterm infants requiring intensive care. 

Methods: this international, open-label, randomised controlled trial was done in 13 neonatal intensive care units in the UK, Spain, and the Netherlands. Infants were included if they were within 24 h of birth, had a birthweight of 1200 g or less, had a gestational age up to 33 weeks plus 6 days, and had parental written informed consent. Infants were randomly assigned (1:1) to real-time CGM or standard care (with masked CGM for comparison) using a central web randomisation system, stratified by recruiting centre and gestational age (<26 or ≥26 weeks). The primary efficacy outcome was the proportion of time sensor glucose concentration was 2·6–10 mmol/L for the first week of life. Safety outcomes related to hypoglycaemia (glucose concentrations <2·6 mmol/L) in the first 7 days of life. All outcomes were assessed on the basis of intention to treat in the full analysis set with available data. The study is registered with the International Standard Randomised Control Trials Registry, ISRCTN12793535. 

Findings: between July 4, 2016, and Jan 27, 2019, 182 infants were enrolled, 180 of whom were randomly assigned (85 to real-time CGM, 95 to standard care). 70 infants in the real-time CGM intervention group and 85 in the standard care group had CGM data and were included in the primary analysis. Compared with infants in the standard care group, infants managed using CGM had more time in the 2·6–10 mmol/L glucose concentration target range (mean proportion of time 84% [SD 22] vs 94% [11]; adjusted mean difference 8·9% [95% CI 3·4–14·4]), equivalent to 13 h (95% CI 5–21). More infants in the standard care group were exposed to at least one episode of sensor glucose concentration of less than 2·6 mmol/L for more than 1 h than those in the intervention group (13 [15%] of 85 vs four [6%] of 70). There were no serious adverse events related to the use of the device or episodes of infection.

 Interpretation: real-time CGM can reduce exposure to prolonged or severe hyperglycaemia and hypoglycaemia. Further studies using CGM are required to determine optimal glucose targets, strategies to obtain them, and the potential effect on long-term health outcomes. Funding: National Institute for Health Research Efficacy and Mechanisms Evaluation Programme.

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e-pub ahead of print date: 10 February 2021
Published date: 17 March 2021
Additional Information: Funding Information: The authors acknowledge and thank all the families who took part in the study and the clinical teams on the tertiary neonatal units for their support. We thank the trial steering committee (independent members Kate Costeloe [Chair], Tim Cole, Andrew Ewer, Peter Watkinson, and Sharon Coaker), the data monitoring and ethics committee (David Field [Chair], Diana Elbourne, and Jane Hawdon), and Tracy Assari from Cambridge University Hospitals (Cambridge, UK) research and development office for their support and belief in us through the challenging times of running a multicentre device trial in this setting. We also acknowledge the support of the National Institute for Health Research (NIHR) Efficacy and Mechanisms Evaluation Programme, the NIHR Cambridge Biomedical Research Centre (Cambridge, UK), and the Evelyn Trust (Cambridge, UK), without whom the studies would not have been possible. We further thank Medtronic (Northridge, CA, USA) for providing the continuous glucose monitoring system and sensors, and Nova Biomedical (Waltham, MA, USA) for the Nova StatStrip point of care devices used in the study. Funding was provided by the NIHR Efficacy and Mechanisms Evaluation Programme and supported by the NIHR Cambridge Biomedical Research Centre and the Cambridge Clinical Trials Unit (Cambridge, UK), and through the portfolio from NIHR Clinical Trials Network Eastern. The study sponsor was the University of Cambridge and Cambridge University Hospitals NHS Trust (Cambridge, UK). Medtronic and Nova Biomedical donated equipment. Neither Medtronic nor Nova Biomedical had any role in design of the study, gathering of data, access to data, preparation of the manuscript, or decision to publish the results. Funding Information: The authors acknowledge and thank all the families who took part in the study and the clinical teams on the tertiary neonatal units for their support. We thank the trial steering committee (independent members Kate Costeloe [Chair], Tim Cole, Andrew Ewer, Peter Watkinson, and Sharon Coaker), the data monitoring and ethics committee (David Field [Chair], Diana Elbourne, and Jane Hawdon), and Tracy Assari from Cambridge University Hospitals (Cambridge, UK) research and development office for their support and belief in us through the challenging times of running a multicentre device trial in this setting. We also acknowledge the support of the National Institute for Health Research (NIHR) Efficacy and Mechanisms Evaluation Programme, the NIHR Cambridge Biomedical Research Centre (Cambridge, UK), and the Evelyn Trust (Cambridge, UK), without whom the studies would not have been possible. We further thank Medtronic (Northridge, CA, USA) for providing the continuous glucose monitoring system and sensors, and Nova Biomedical (Waltham, MA, USA) for the Nova StatStrip point of care devices used in the study. Funding was provided by the NIHR Efficacy and Mechanisms Evaluation Programme and supported by the NIHR Cambridge Biomedical Research Centre and the Cambridge Clinical Trials Unit (Cambridge, UK), and through the portfolio from NIHR Clinical Trials Network Eastern. The study sponsor was the University of Cambridge and Cambridge University Hospitals NHS Trust (Cambridge, UK). Medtronic and Nova Biomedical donated equipment. Neither Medtronic nor Nova Biomedical had any role in design of the study, gathering of data, access to data, preparation of the manuscript, or decision to publish the results. Publisher Copyright: © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Identifiers

Local EPrints ID: 477405
URI: http://eprints.soton.ac.uk/id/eprint/477405
ISSN: 2352-4650
PURE UUID: cf0e9a96-9875-4863-989f-f6cd5ba6efc8
ORCID for Mark Johnson: ORCID iD orcid.org/0000-0003-1829-9912

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Date deposited: 06 Jun 2023 16:43
Last modified: 18 Mar 2024 03:47

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Contributors

Author: Kathryn Beardsall
Author: Lynn Thomson
Author: Catherine Guy
Author: Isabel Iglesias-Platas
Author: Mirjam M. van Weissenbruch
Author: Simon Bond
Author: Annabel Allison
Author: Sungwook Kim
Author: Stavros Petrou
Author: Beatrice Pantaleo
Author: Roman Hovorka
Author: David Dunger
Author: Zoltan Molnar
Author: Sheula Barlow
Author: Sharon Baugh
Author: Kathryn A. Johnson
Author: Lindsay Uryn
Author: Collette Spencer
Author: Maria Hubbard
Author: Sateeshkumar Somisetty
Author: Olaitan Adesiyan
Author: Jogesh Kapadia
Author: Yvonne Millar
Author: Kalyana Gurusamy
Author: Lindsay Bibb
Author: Kathryn Jones
Author: Richard Heaver
Author: Priya Muthukumar
Author: Amy Nichols
Author: Mark Johnson ORCID iD
Author: Jenny Pond
Author: Philippa Crowley
Author: Christie Mellish
Author: Divyen D. Shah
Author: Mercy Abraham
Author: Presillina Vincent
Author: Suma Anil kumar
Author: Angelina Iringan
Author: Barbara Aninakwa
Author: R. A. Dalangin-Chalmers
Author: Annemieke de Lange
Corporate Author: REACT collaborative

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