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.

中文翻译：

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早产儿实时连续血糖监测 (REACT)：一项国际、开放标签、随机对照试验

背景

高血糖症和低血糖症在早产儿中很常见，并且与死亡率和发病率的增加有关。由于很少测量血糖浓度，降低与这些暴露相关的风险的干预措施尤其具有挑战性，有可能造成更多伤害而不是改善这些婴儿的结果。连续血糖监测 (CGM) 广泛用于成人和儿童糖尿病以改善血糖控制，但尚未批准用于新生儿。REACT 试验旨在评估 CGM 在需要重症监护的早产儿中的有效性和安全性。

方法

这项国际、开放标签、随机对照试验在英国、西班牙和荷兰的 13 个新生儿重症监护室进行。如果婴儿出生后 24 小时内，出生体重不超过 1200 克，胎龄不超过 33 周加 6 天，并且有父母的书面知情同意书，则包括在内。使用中央网络随机系统将婴儿 (1:1) 随机分配到实时 CGM 或标准护理（使用隐蔽 CGM 进行比较），按招募中心和胎龄（<26 或≥26 周）分层。主要疗效结果是生命第一周时间传感器葡萄糖浓度的比例为 2·6-10 mmol/L。与出生后前 7 天低血糖（葡萄糖浓度 <2·6 mmol/L）相关的安全性结果。所有结局均根据可用数据在完整分析集中的治疗意向进行评估。该研究已在国际标准随机对照试验注册中心 ISRCTN12793535 注册。

发现

2016 年 7 月 4 日至 2019 年 1 月 27 日期间，共有 182 名婴儿入组，其中 180 名被随机分配（实时 CGM 85 名，标准护理 95 名）。实时 CGM 干预组的 70 名婴儿和标准护理组的 85 名婴儿有 CGM 数据并被纳入主要分析。与标准护理组的婴儿相比，使用 CGM 管理的婴儿在 2·6-10 mmol/L 葡萄糖浓度目标范围内有更多的时间（平均时间比例 84% [SD 22] vs 94% [11]；调整后的平均差异 8·9% [95% CI 3·4–14·4]），相当于 13 小时（95% CI 5-21）。与干预组相比，标准护理组中的婴儿暴露于至少 1 次传感器葡萄糖浓度低于 2·6 mmol/L 且持续时间超过 1 小时（13 [15%] of 85 vs四 [6%] 的 70）。没有与设备使用或感染发作相关的严重不良事件。

解释

实时 CGM 可以减少暴露于长期或严重的高血糖和低血糖。需要使用 CGM 进行进一步研究以确定最佳葡萄糖目标、获得它们的策略以及对长期健康结果的潜在影响。

资金

国家卫生研究所效力和机制评估计划。