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

Beardsall, Kathryn; Thomson, Lynn; Guy, Catherine; Iglesias-Platas, Isabel; Weissenbruch, Mirjam M. van; Bond, Simon; Allison, Annabel; Kim, Sung-Wook; Petrou, Stavros; Pantaleo, Beatrice; Hovorka, Roman; Dunger, David; Molnár, Zoltán; Barlow, Sheula; Baugh, Sharon; Johnson, Kathryn A.; Uryn, Lindsay; Spencer, Collette; Hubbard, Maria; Somisetty, Sateeshkumar; Adesiyan, Olaitan; Kapadia, Jogesh; Millar, Yvonne; Gurusamy, Kalyana; Bibb, Lindsay; Jones, Kathryn M.; Heaver, Richard; Muthukumar, P; Nichols, Allen B.; Johnson, Mark; Pond, Jenny; Crowley, Philippa; Mellish, C. H.; Shah, Divyen D; Abraham, Mercy; Vincent, Presillina; kumar, Suma Anil; Iringan, Angelina; Aninakwa, Barbara; Dalangin-Chalmers, R A; Lange, Annemieke de

doi:10.1016/s2352-4642(20)30367-9

Cited by 49 publications

(34 citation statements)

References 29 publications

(46 reference statements)

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“…Monitoring of glucose levels in preterm infants is often infrequent, and studies using CGM have shown that real time CGM alone, or in combination with computer algorithms, has the potential to reduce the prevalence of hyperglycaemia without increasing the risk of hypoglycaemia ( 91 , 109 ). Furthermore, a recent international multicentre trial has demonstrated that the use of CGM in preterm infants can safely support the targeting of glucose control without causing hypoglycaemia, and is cost effective ( 110 , 111 ). However, optimal target glucose levels remain to be determined.…”

Section: Hyperglycaemia In the Preterm Infantmentioning

confidence: 99%

Hyperglycaemia in the Newborn Infant. Physiology Verses Pathology

Beardsall

2021

Front. Pediatr.

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Hyperglycemia is common in newborns requiring intensive care, particularly in preterm infants, in sepsis and following perinatal hypoxia. The clinical significance, and optimal intervention strategy varies with context, but hyperglycaemia is associated with increased mortality and morbidity. The limited evidence for optimal clinical targets mean controversy remains regarding thresholds for intervention, and management strategies. The first consideration in the management of hyperglycaemia must be to ascertain potentially treatable causes. Calculation of the glucose infusion rate (GIR) to insure this is not excessive, is critical but the use of insulin is often helpful in the extremely preterm infant, but is associated with an increased risk of hypoglycaemia. The use of continuous glucose monitoring (CGM) has recently been demonstrated to be helpful in targeting glucose control, and reducing the risk from hypoglycaemia in the preterm infant. Its use in other at risk infants remains to be explored, and further studies are needed to provide a better understanding of the optimal glucose targets for different clinical conditions. In the future the combination of CGM and advances in computer algorithms, to provide intelligent closed loop systems, could allow a safer and more personalized approached to management.

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Section: Hyperglycaemia In the Preterm Infantmentioning

confidence: 99%

Hyperglycaemia in the Newborn Infant. Physiology Verses Pathology

Beardsall

2021

Front. Pediatr.

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“…A shining example of a medical wearable with undoubted proven clinical benefit is the real-time continuous glucose monitoring device. Multinational, multicentre RCTs have demonstrated reduced exposure to prolonged or severe hyperglycaemia and hypoglycaemia and less severe adverse events, both in adolescents 6 as well as in preterm neonates 7 . Similarly, Palmer et al recently provided an impressive real-world example for the enormous potential of integrated antenatal care using telehealth 8 .…”

Section: Paediatric Healthcare Providers and Biomedical Researchers Should Embrace Digital Innovations To Improve Child Healthmentioning

confidence: 99%

Viewpoint: digital paediatrics—so close yet so far away

Hensel

Powell

2021

Arch Dis Child

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Technology is driving a revolution in healthcare, but paediatric services have not fully harnessed the potential. Digital health solutions yet to achieve their promise in paediatrics include electronic health records, decision support systems, telemedicine and remote consultations, despite the accelerated uptake during the COVID-19 pandemic. There are also significant potential benefits in digitally enabled research, including systems to identify and recruit participants online or through health records, tools to extract data points from routine data sets rather than new data collection, and remote approaches to outcome measurement. Children and their families are increasingly becoming digital health citizens, able to manage their own health and use of health services through mobile apps and wearables such as fitness trackers. Ironically, one barrier to the uptake of these technologies is that the fast pace of change in this area means the evidence base behind many of these tools remains underdeveloped. Clinicians are often sceptical of innovations which appear largely driven by enthusiasts rather than science. Rigorous studies are needed to demonstrate safety and effectiveness. Regulators need to be agile and responsive. Implementation needs adequate resource and time, and needs to minimise risks and address concerns, such as worries over losing human contact. Digital health care needs to be embedded in medical education and training so that clinicians are trained in the use of innovations and can understand how to embed within services. In this way, digital paediatrics can deliver benefits to the profession, to services and to our patients.

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“…This used block randomisation, with blocks of random size (i.e. 4,6,8) stratifying by recruiting centre and gestation (< 26 or ≥ 26 weeks' gestation). The management of glucose control and use of CGM from recruitment at aged ≤ 24 hours until day 7 were predetermined in the protocol for each study arm.…”

Section: Randomisation and Blindingmentioning

confidence: 99%

“…Randomised controlled trial: model-fitting resultssensitivity analyses of the primary outcome (continued ) Reproduced with permission from Beardsall et al4 in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.…”

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Continuous glucose monitoring in extremely preterm infants in intensive care: the REACT RCT and pilot study of ‘closed-loop’ technology

et al. 2021

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Background Hyperglycaemia and hypoglycaemia are common in preterm infants and are associated with increased mortality and morbidity. Continuous glucose monitoring is widely used to target glucose control in adults and children, but not in neonates. Objective To evaluate the role of continuous glucose monitoring in the preterm infant. Design The REAl-time Continuous glucose moniToring in neonatal intensive care project combined (1) a feasibility study, (2) a multicentre randomised controlled trial and (3) a pilot of ‘closed-loop’ continuous glucose monitoring. The feasibility study comprised a single-centre study (n = 20). Eligibility criteria included a birthweight ≤ 1200 g and aged ≤ 48 hours. Continuous glucose monitoring was initiated to support glucose control. The efficacy and safety outcomes guided the design of the randomised controlled trial. The randomised controlled trial comprised a European multicentre trial (n = 182). Eligibility criteria included birthweight ≤ 1200 g and aged ≤ 24 hours. Exclusion criteria included any lethal congenital abnormality. Continuous glucose monitoring was initiated to support glucose control within 24 hours of birth. In the intervention group, the continuous glucose monitoring sensor provided real-time data on glucose levels, which guided clinical management. In control infants, the continuous glucose monitoring data were masked, and glucose level was managed in accordance with standard clinical practice and based on the blood glucose levels. The primary outcome measure was the percentage of time during which the sensor glucose level was within the target range of 2.6–10 mmol/l. Secondary outcome measures included mean sensor glucose level, the percentage of time during which the sensor glucose level was within the target range of 4–8 mmol/l, the percentage of time during which the sensor glucose level was in the hyperglycaemic range (i.e. > 15 mmol/l) and sensor glucose level variability. Safety outcomes included hypoglycaemia exposure. Acceptability assessment and health economic analyses were carried out and further exploratory health outcomes were explored. The mean percentage of time in glucose target range of 2.6–10 mmol/l was 9% higher in infants in the continuous glucose monitoring group (95% confidence interval 3% to 14%; p = 0.002), and the mean time in the target range of 4–8 mmol/l was 12% higher in this group (95% confidence interval 4% to 19%; p = 0.004). There was no difference in the number of episodes of hypoglycaemia. Exploratory outcomes showed a reduced risk of necrotising enterocolitis in the intervention arm (odds ratio 0.33, 95% confidence interval 0.13 to 0.78; p = 0.01). Health economic analyses demonstrated that continuous glucose monitoring was cost-effective on the basis of the cost per additional case of adequate glucose control between 2.6 and 10 mmol/l. The ‘closed-loop’ study was a single-center pilot study, with eligibility criteria including a birthweight of ≤ 1200 g and aged ≤ 48 hours. Infants underwent continuous glucose monitoring for the first week of life (n = 21), with those in the intervention group receiving closed-loop insulin delivery between 48 and 72 hours of age. The primary outcome of percentage of time in the target range (i.e. sensor glucose 4–8 mmol/l) increased from a median of 26% (interquartile range 6–64%) to 91% (interquartile range 78–99%) during closed-loop insulin delivery (p < 0.001). Limitations These studies have not defined the optimal targets for glucose control or the best strategies to achieve them in these infants. Future work Studies are needed to evaluate the longer-term impact of targeting glucose control on clinical outcomes. Conclusions Continuous glucose monitoring in extremely preterm infants can improve glucose control, with closed-loop insulin delivery having further potential to target glucose levels. Staff and parents felt that the use of continuous glucose monitoring improved care and the results of the health economic evaluation favours the use of continuous glucose monitoring. Trial registration Current Controlled Trials ISRCTN12793535. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 16. See the NIHR Journals Library website for further project information. Medtronic plc provided some MiniMed™ 640G systems and Nova Biomedical (Waltham, MA, USA) provided point-of-care devices.

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

Cited by 49 publications

References 29 publications

Hyperglycaemia in the Newborn Infant. Physiology Verses Pathology

Hyperglycaemia in the Newborn Infant. Physiology Verses Pathology

Viewpoint: digital paediatrics—so close yet so far away

Continuous glucose monitoring in extremely preterm infants in intensive care: the REACT RCT and pilot study of ‘closed-loop’ technology

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