The Effect of an Additional Pre-extubational Loading Dose of Caffeine-citrate

Summary

The goal of this clinical trial is to answer whether the use of a single loading dose (20 mg/kg) of caffeine citrate one hour before extubation has an impact on the success rate of extubation among preterm neonates. In addition, the investigators would like to assess the frequency of apneas and side effects of the intervention, as well as the development of NEC, BPD, IVH, PVL, and long-term neurodevelopmental outcomes in the investigated populations. According to institutional protocol, preterm infants born before the 32nd week of gestation receive a standard dose of caffeine citrate therapy. This covers a maintenance dose of 5-10 mg/kg of caffeine citrate administered intravenously once or twice daily after a loading dose of 20 mg/kg on the first day of life. In this trial, preterm infants born before the 32nd gestational week and who had been mechanically ventilated for at least 48 hours before planned extubation are planned to be randomly allocated into intervention and control groups. The intervention group will receive an additional loading dose of caffeine citrate 60 minutes before extubation. The control group will receive standard dosing regimens.

Timeline

Start

2023-12-21

Primary completion

2027-12

Completion

2028-12

Publications

• Background Erickson G, Dobson NR, Hunt CE. Immature control of breathing and apnea of prematurity: the known and unknown. J Perinatol. 2021 Sep;41(9):2111-2123. doi: 10.1038/s41372-021-01010-z. Epub 2021 Mar 12.
• Background Bacci SLLDS, Johnston C, Hattori WT, Pereira JM, Azevedo VMGO. Mechanical ventilation weaning practices in neonatal and pediatric ICUs in Brazil: the Weaning Survey-Brazil. J Bras Pneumol. 2020 Mar 23;46(4):e20190005. doi: 10.36416/1806-3756/e20190005. eCollection 2020.
• Background Kreutzer K, Bassler D. Caffeine for apnea of prematurity: a neonatal success story. Neonatology. 2014;105(4):332-6. doi: 10.1159/000360647. Epub 2014 May 30.
• Background Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056/NEJMoa054065.
• Background Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med. 2007 Nov 8;357(19):1893-902. doi: 10.1056/NEJMoa073679.
• Background Eichenwald EC. National and international guidelines for neonatal caffeine use: Are they evidenced-based? Semin Fetal Neonatal Med. 2020 Dec;25(6):101177. doi: 10.1016/j.siny.2020.101177. Epub 2020 Nov 4.
• Background Moschino L, Zivanovic S, Hartley C, Trevisanuto D, Baraldi E, Roehr CC. Caffeine in preterm infants: where are we in 2020? ERJ Open Res. 2020 Mar 2;6(1):00330-2019. doi: 10.1183/23120541.00330-2019. eCollection 2020 Jan.
• Background Chen J, Jin L, Chen X. Efficacy and Safety of Different Maintenance Doses of Caffeine Citrate for Treatment of Apnea in Premature Infants: A Systematic Review and Meta-Analysis. Biomed Res Int. 2018 Dec 24;2018:9061234. doi: 10.1155/2018/9061234. eCollection 2018.
• Background Mohammed S, Nour I, Shabaan AE, Shouman B, Abdel-Hady H, Nasef N. High versus low-dose caffeine for apnea of prematurity: a randomized controlled trial. Eur J Pediatr. 2015 Jul;174(7):949-56. doi: 10.1007/s00431-015-2494-8. Epub 2015 Feb 3.
• Background McPherson C, Neil JJ, Tjoeng TH, Pineda R, Inder TE. A pilot randomized trial of high-dose caffeine therapy in preterm infants. Pediatr Res. 2015 Aug;78(2):198-204. doi: 10.1038/pr.2015.72. Epub 2015 Apr 9.
• Background Chavez L, Bancalari E. Caffeine: Some of the Evidence behind Its Use and Abuse in the Preterm Infant. Neonatology. 2022;119(4):428-432. doi: 10.1159/000525267. Epub 2022 Jun 10.
• Background Long JY, Guo HL, He X, Hu YH, Xia Y, Cheng R, Ding XS, Chen F, Xu J. Caffeine for the Pharmacological Treatment of Apnea of Prematurity in the NICU: Dose Selection Conundrum, Therapeutic Drug Monitoring and Genetic Factors. Front Pharmacol. 2021 Jul 26;12:681842. doi: 10.3389/fphar.2021.681842. eCollection 2021.
• Kovacs K, Nagy R, Andreka L, Teutsch B, Szabo M, Varga P, Hegyi P, Harsfalvi P, Acs N, Harmath A, Nador C, Gasparics A. The effect of an additional pre-extubational loading dose of caffeine citrate on mechanically ventilated preterm infants (NEOKOFF trial): Study protocol for a multicenter randomized clinical trial. PLoS One. 2025 Jan 13;20(1):e0315856. doi: 10.1371/journal.pone.0315856. eCollection 2025.

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