Kovács Kinga, Nagy Rita, Andréka Lilla, Teutsch Brigitta, Szabó Miklós, Varga Péter, Hegyi Péter, Hársfalvi Péter, Ács Nándor, Harmath Ágnes, Nádor Csaba, Gasparics Ákos
Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
PLoS One. 2025 Jan 13;20(1):e0315856. doi: 10.1371/journal.pone.0315856. eCollection 2025.
Minimizing the duration of mechanical ventilation is one of the most important therapeutic goals during the care of preterm infants at neonatal intensive care units (NICUs). The rate of extubation failure among preterm infants is between 16% and 40% worldwide. Numerous studies have been conducted on the assessment of extubation suitability, the optimal choice of respiratory support around extubation, and the effectiveness of medical interventions. Since the Caffeine Therapy for Apnea of Prematurity (CAP) trial, caffeine has become one of the essential drugs at NICUs. However, the optimal dosage and timing for adequate effectiveness still need to be more conclusive. Previous studies suggest that higher doses of caffeine treatment increase the success rate of extubation. Therefore, we aim to determine whether using a single additional loading dose of caffeine citrate one hour prior to extubation impacts the success rate of extubation.
The study is an open-label, multicenter randomized clinical trial testing the effectiveness and safety of pre-extubational loading dose of caffeine citrate. Inclusion criteria will be infants born before the 32nd gestational week, before the first extubation attempt after at least 48 hours of mechanical ventilation, and a signed parental informed consent. A total of 226 patients will be randomly allocated to either the experimental or control group. The randomization will be stratified by gestational age and antenatal steroid prophylaxis. Preterm infants in the experimental group will receive an additional intravenous (IV) loading dose (20 mg/kg) of caffeine citrate one hour before the first planned extubation, in addition to the standard dosing regimen (20 mg/kg caffeine citrate IV on the first day of life and 5 to 10 mg/kg IV or orally caffeine citrate each consecutive day). Preterm infants in the control group will receive the standard dosing regimen. The primary outcome will be reintubation within 48 hours.
A pre-extubational loading dose of caffeine citrate can reduce extubation failure. Obtaining evidence on this feature has the potential to contribute to finding the optimal dosing regimen.
The study protocol was approved by the Hungarian Ethics Committee for Clinical Pharmacology of the Medical Research Council and National Institute of Pharmacy and Nutrition (OGYÉI/6838-11/2023). ClinicalTrials.gov identifier NCT06401083 Registered 06. May 2024.; EudraCT number: 2022-003202-77.
在新生儿重症监护病房（NICU）护理早产儿期间，尽量缩短机械通气时间是最重要的治疗目标之一。全球范围内，早产儿拔管失败率在16%至40%之间。关于拔管适宜性评估、拔管前后呼吸支持的最佳选择以及医学干预措施的有效性，已经开展了大量研究。自早产新生儿咖啡因治疗呼吸暂停（CAP）试验以来，咖啡因已成为NICU的基本用药之一。然而，达到充分疗效的最佳剂量和给药时间仍有待更确凿的定论。此前的研究表明，更高剂量的咖啡因治疗可提高拔管成功率。因此，我们旨在确定在拔管前一小时额外使用一剂枸橼酸咖啡因负荷剂量是否会影响拔管成功率。
本研究为开放标签、多中心随机临床试验，旨在测试拔管前枸橼酸咖啡因负荷剂量的有效性和安全性。纳入标准为孕32周前出生、在机械通气至少48小时后首次尝试拔管前、且父母签署知情同意书的婴儿。总共226名患者将被随机分配至试验组或对照组。随机分组将按胎龄和产前类固醇预防用药情况进行分层。试验组的早产儿在首次计划拔管前一小时，除标准给药方案（出生第一天静脉注射20mg/kg枸橼酸咖啡因，随后每天静脉注射或口服5至10mg/kg枸橼酸咖啡因）外，还将额外接受一剂静脉注射（20mg/kg）枸橼酸咖啡因负荷剂量。对照组的早产儿将接受标准给药方案。主要结局指标为48小时内再次插管。
拔管前使用枸橼酸咖啡因负荷剂量可降低拔管失败率。获取这一特性的证据可能有助于找到最佳给药方案。
本研究方案已获得匈牙利医学研究委员会临床药理学伦理委员会以及国家药学与营养研究所（OGYÉI/6838-11/2023）的批准。ClinicalTrials.gov标识符：NCT06401083，于2024年5月6日注册；欧盟临床试验注册号：2022-003202-77。
