Oliphant Elizabeth Anne, McKinlay Christopher J D, McNamara David G, Alsweiler Jane Marie
Department of Paediatrics: Child and Youth Health, The University of Auckland, Auckland, New Zealand
Newborn Services, Starship Children's Health, Auckland District Health Board, Auckland, New Zealand.
BMJ Open. 2020 Oct 20;10(10):e038271. doi: 10.1136/bmjopen-2020-038271.
Infants born late preterm (34+0 to 36+6 weeks' gestational age) have frequent episodes of intermittent hypoxaemia compared with term infants. Caffeine citrate reduces apnoea and intermittent hypoxaemia and improves long-term neurodevelopmental outcomes in infants born very preterm and may have similar effects in late preterm infants. Clearance of caffeine citrate increases with gestational age and late preterm infants are likely to need a higher dose than very preterm infants. Our aim is to determine the most effective and best-tolerated dose of caffeine citrate to reduce transient intermittent hypoxaemia events in late preterm infants.
A phase IIB, double-blind, five-arm, parallel, randomised controlled trial to compare the effect of four doses of oral caffeine citrate versus placebo on the frequency of intermittent hypoxaemia. Late preterm infants will be enrolled within 72 hours of birth and randomised to receive 5, 10, 15 or 20 mg/kg/day caffeine citrate or matching placebo daily until term corrected age. The frequency of intermittent hypoxaemia (events/hour where oxygen saturation concentration is ≥10% below baseline for ≤2 min) will be assessed with overnight oximetry at baseline, 2 weeks after randomisation (primary outcome) and at term corrected age. Growth will be measured at these timepoints, and effects on feeding and sleeping will be assessed by parental report. Data will be analysed using generalised linear mixed models.
This trial has been approved by the Health and Disability Ethics Committees of New Zealand (reference 18/NTA/129) and the local institutional research review committees. Findings will be disseminated to peer-reviewed journals to clinicians and researchers at local and international conferences and to the public. The findings of the trial will inform the design of a large multicentre trial of prophylactic caffeine in late preterm infants, by indicating the most appropriate dose to use and providing information on feasibility.
ACTRN12618001745235; Pre-results.
与足月儿相比，晚期早产儿（胎龄34⁺⁰至36⁺⁶周）频发间歇性低氧血症。枸橼酸咖啡因可减少呼吸暂停和间歇性低氧血症，并改善极早产儿的长期神经发育结局，对晚期早产儿可能有类似作用。枸橼酸咖啡因的清除率随胎龄增加，晚期早产儿可能比极早产儿需要更高剂量。我们的目的是确定枸橼酸咖啡因减少晚期早产儿短暂间歇性低氧血症事件的最有效且耐受性最佳的剂量。
一项IIB期、双盲、五臂、平行、随机对照试验，比较四种剂量口服枸橼酸咖啡因与安慰剂对间歇性低氧血症频率的影响。晚期早产儿将在出生后72小时内入组，随机接受5、10、15或20mg/kg/天的枸橼酸咖啡因或匹配的安慰剂，每日给药直至矫正胎龄足月。间歇性低氧血症频率（血氧饱和度浓度低于基线≥10%且持续时间≤2分钟的事件数/小时）将在基线、随机分组后2周（主要结局）和矫正胎龄足月时通过夜间血氧测定进行评估。在这些时间点测量生长情况，并通过家长报告评估对喂养和睡眠的影响。数据将使用广义线性混合模型进行分析。
本试验已获得新西兰健康与残疾伦理委员会（参考号18/NTA/129）和当地机构研究审查委员会的批准。研究结果将发表在同行评审期刊上，在当地和国际会议上向临床医生和研究人员以及公众传播。该试验的结果将通过指出最适宜的使用剂量并提供可行性信息，为晚期早产儿预防性咖啡因大型多中心试验的设计提供依据。
ACTRN12618001745235；预结果。
