Continuous Glucose Monitoring in HIE

Official title

Real-time Continuous Glucose Monitoring in Infants With Hypoxic-ischaemic Encephalopathy: a Pilot Randomized Controlled Trial

Overview

The aim of the study is to examine whether the use of continuous glucose monitoring (CGM) to guide the clinical management of glycaemic control will result into an increased time in the target glucose concentration. To further examine the efficacy of using CGM the following secondary outcomes in the two groups were assessed: mean glucose values, glucose variability within individuals, percentage of time that glucose values are in hyperglycaemic or hypoglycaemic ranges. Randomized controlled trial recruiting neonates (Birth weight \>1.8kg, Gestation\>36 weeks) with moderate or severe hypoxic ischemic encephalopathy (HIE) following perinatal asphyxia . Neonates will be randomly assigned (1:1) within 6 hours of birth to receive either the intervention with real-time CGM or standard care for 72 hours.

Detailed description

Neonatal hypoglycaemia and hyperglycaemia are associated with brain injury and impaired neurodevelopment outcomes in neonates with HIE. Improving early glucose control is an important modifiable risk factor for outcomes in this population. Glycaemic monitoring is usually performed by capillary or central line sampling. However, over 30% of the episodes of abnormal glucose concentration are undetected, even with regular but intermittent sampling. CGM can allow earlier detection and prevention of exposure to extreme glucose concentrations.

Study design - This is a multicentre interventional, open-label, randomized controlled trial of CGM compared with standard clinical management (control).A total of 70 neonates (Birth weight \>1.8kg, Gestation \>36 weeks and aged \<6hours) with moderate or severe HIE following perinatal asphyxia will be recruited within 6 hours of birth after informed parental consent. Neonates with major congenital malformations, inborn errors of metabolism, congenital infections, imminent death will be excluded.

Neonates will be randomly assigned (1:1) to receive either the intervention with real-time CGM for 72 hours or standard care using a randomization program (R package SRS: A Subject Randomization System). We will use the minimization method to control for severity and to achieve balance within recruiting centres. In all the neonates recruited Dexcom ONE+ CGM (Dexcom, San Diego, CA, USA) will be placed soon after study enrollment. The sensors will be inserted in the lateral thigh and continuous measurements will be recorded for 72 h. The CGM device will be calibrated using blood glucose values measured by point-of-care test. CGM calibrations will be performed at least twice a day. CGM data will be downloaded by using Dexcom Studio software on a dedicated computer.

In the standard care group, the CGM device will collect glucose data continuously, but the clinical team will be blinded to the data. These neonates will have their glucose control monitored and managed according to standard clinical practice using intermittently sampled blood glucose levels. In the intervention group the CGM data will be used to support clinical management including blood glucose measurements and decision making. Changes in glucose and insulin infusion will be based primarily on the real-time CGM data but blood glucose concentrations will be checked in case of rapid changes in CGM data.

Interventions to target glucose control will be guided by a protocol shared among the participating hospitals. As part of the study protocol, all the neonates will receive a continuous infusion of glucose 10% of 3-4 mg/kg/minute and total fluid intake starting at 50-60 ml/kg/day followed by titration depending on urine output, renal function, and management of glucose infusion rates.

Interventions

• Device Dexcom ONE+
  In all the neonates recruited CGM sensor and transmitter will be placed soon after study enrollment. The sensors will be inserted in the lateral thigh and continuous measurements will be recorded for all the duration of therapeutic hypothermia.

Primary outcome measures

• In range - time [Time frame: 72 hours after birth]

Secondary outcome measures (4)

• Hypoglycemia [Time frame: 72 hours after birth]
• Hyperglycemia [Time frame: 72 hours after birth]
• Glycemic variability [Time frame: 72 hours after birth]
• Adverse events associated to insertion of CGM [Time frame: up to 10 days after birth]

Eligibility criteria

Inclusion criteria

• Birth weight >1.8kg
• Gestation >35 weeks
• Aged <6hours
• Moderate or severe HIE following perinatal asphyxia

Exclusion criteria

• Major congenital malformations
• Inborn errors of metabolism,
• Congenital infections
• Imminent death

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Diagnostic

Study locations

Italy · 3 centers

• A.O.S.G. Moscati — Avellino
• University of Campania Luigi Vanvitelli — Naples
• Monaldi | | AORN - Ospedali dei ColliAORN - Ospedali dei Colli — Naples

Publications

• Kalogeropoulou MS, Thomson L, Beardsall K. Continuous glucose monitoring during therapeutic hypothermia for hypoxic ischaemic encephalopathy: a feasibility study. Arch Dis Child Fetal Neonatal Ed. 2023 May;108(3):309-315. doi: 10.1136/archdischild-2022-324593. Epub 2022 Dec 20. PMID 36600516
• Pinchefsky EF, Hahn CD, Kamino D, Chau V, Brant R, Moore AM, Tam EWY. Hyperglycemia and Glucose Variability Are Associated with Worse Brain Function and Seizures in Neonatal Encephalopathy: A Prospective Cohort Study. J Pediatr. 2019 Jun;209:23-32. doi: 10.1016/j.jpeds.2019.02.027. Epub 2019 Apr 11. PMID 30982528
• Montaldo P, Caredda E, Pugliese U, Zanfardino A, Delehaye C, Inserra E, Capozzi L, Chello G, Capristo C, Miraglia Del Giudice E, Iafusco D. Continuous glucose monitoring profile during therapeutic hypothermia in encephalopathic infants with unfavorable outcome. Pediatr Res. 2020 Aug;88(2):218-224. doi: 10.1038/s41390-020-0827-4. Epub 2020 Mar 2. PMID 32120381
• Mietzsch U, Wood TR, Wu TW, Natarajan N, Glass HC, Gonzalez FF, Mayock DE, Comstock BA, Heagerty PJ, Juul SE, Wu YW; HEAL Study Group. Early Glycemic State and Outcomes of Neonates With Hypoxic-Ischemic Encephalopathy. Pediatrics. 2023 Oct 1;152(4):e2022060965. doi: 10.1542/peds.2022-060965. PMID 37655394
• Parmentier CEJ, de Vries LS, van der Aa NE, Eijsermans MJC, Harteman JC, Lequin MH, Swanenburg de Veye HFN, Koopman-Esseboom C, Groenendaal F. Hypoglycemia in Infants with Hypoxic-Ischemic Encephalopathy Is Associated with Additional Brain Injury and Worse Neurodevelopmental Outcome. J Pediatr. 2022 Jun;245:30-38.e1. doi: 10.1016/j.jpeds.2022.01.051. Epub 2022 Feb 2. PMID 35120986
• Basu SK, Kaiser JR, Guffey D, Minard CG, Guillet R, Gunn AJ; CoolCap Study Group. Hypoglycaemia and hyperglycaemia are associated with unfavourable outcome in infants with hypoxic ischaemic encephalopathy: a post hoc analysis of the CoolCap Study. Arch Dis Child Fetal Neonatal Ed. 2016 Mar;101(2):F149-55. doi: 10.1136/archdischild-2015-308733. Epub 2015 Aug 17. PMID 26283669
• Tam EWY, Kamino D, Shatil AS, Chau V, Moore AM, Brant R, Widjaja E. Hyperglycemia associated with acute brain injury in neonatal encephalopathy. Neuroimage Clin. 2021;32:102835. doi: 10.1016/j.nicl.2021.102835. Epub 2021 Sep 28. PMID 34601311
• Puzone S, Diplomatico M, Caredda E, Maietta A, Miraglia Del Giudice E, Montaldo P. Hypoglycaemia and hyperglycaemia in neonatal encephalopathy: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2023 Dec 15;109(1):18-25. doi: 10.1136/archdischild-2023-325592. PMID 37316160

Identifiers

NCT: NCT06563687 · SecondUNI84

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗