The Effect of an Additional Pre-extubational Loading Dose of Caffeine-citrate
NCT ID: NCT06401083
Last Updated: 2024-05-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE4
226 participants
INTERVENTIONAL
2023-12-21
2028-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Early Caffeine in Preterm Neonates
NCT03086473
Caffeine as an Adjuvant Therapy for Late Preterm Infants With Respiratory Distress
NCT06026163
Improving Preterm Kidney Outcomes With Caffeine
NCT07262060
Caffeine Citrate to Improve Neonatal Outcomes.
NCT06972849
The Effect of Caffeine Therapy in Cardiovascular Stability in Preterm Neonates at Assiut University Children Hospital NICU
NCT07274969
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
The apnea-reducing effects of the respiratory center stimulant methylxanthines have been known for more than 40 years. Based on current knowledge, caffeine is the drug of choice for the medical treatment of apnea. Caffeine has the narrowest spectrum of side effects, the broadest therapeutic range, and the most prolonged half-life among methylxanthines.
Caffeine is currently one of the most commonly used drugs in premature neonatal intensive care units. The most common dosing recommendation is a maintenance dose of 5-10 mg/kg daily after a loading dose of 20 mg/kg of caffeine citrate. Higher saturating and maintenance doses have been used in some studies, with some reports suggesting that higher doses of caffeine increase the chance of successful extubation. However, other studies have reported more frequent adverse effects at higher doses. Conflicting literature suggests that caffeine dosing may vary between institutions. Further basic research and clinical studies are needed to determine the optimal dose.
The investigators seek to answer whether the use of a single loading dose of caffeine citrate one hour before extubation impacts the success rate of extubation. In addition, the investigators would like to assess the frequency and severity of side effects and the development of necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, and bronchopulmonary dysplasia.
To investigate the effect of a pre-extubational loading dose of caffeine-citrate, the investigators plan to carry out a two-armed randomized clinical trial, including preterm neonates being treated in one of the tertiary neonatal intensive care units of Semmelweis University. A total of 226 patients are planned to be enrolled. According to institutional protocol, preterm infants born before the 32nd week of gestation receive a standard dose of caffeine 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.
Preterm infants who have been on mechanical ventilation for at least 48 hours before planned extubation will be randomly allocated into intervention and control groups. Stratification of the randomization will be based on gestational age and antenatal steroid prophylaxis. Intervention is an additional loading dose (20 mg/kg) of intravenous caffeine citrate 60 minutes before extubation. The control group will receive routine dosing regimens as mentioned above. Before extubation, the parents will be informed and asked for consent. Pre-interventional, the investigators plan to collect baseline characteristics and oxygen requirements. After extubation, the need for reintubation within the next 48 hours will be assessed. This timeframe was chosen because most of reintubation due to respiratory reasons happens within the next 48 hours after extubation, and the caffeine half-life ranges from 40 to 230 hours.
The investigators will also assess the frequency of side effects such as gastric residuals, frequency of apneas, need for supplementary oxygen, elevated heart rate, or blood pressure. Data will be collected about adverse outcomes of prematurity, e.g., necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, and bronchopulmonary dysplasia.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Pre-extubational caffeine-citrate
Participants will receive 20 mg/kg loading dose of caffeine citrate on the first day of life and after that 5-10 mg/kg maintenance dose each day. On this arm, the participants will receive 20 mg/kg caffeine dose once again before the planned extubation.
Caffeine citrate
20 mg/kg caffeine-citrate before the planned extubation.
Routine care
Participants will receive 20 mg/kg loading dose of caffeine citrate on the first day of life and after that 5-10 mg/kg maintenance dose each day, also on the day of the extubation.
No interventions assigned to this group
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Caffeine citrate
20 mg/kg caffeine-citrate before the planned extubation.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Had been mechanically ventilated for at least 48 hours;
* Before the first planned extubation.
Exclusion Criteria
* Major congenital anomaly;
* Had not received surfactant treatment;
* Hydrops foetalis;
* Persistent tachycardia before extubation, fetal/neonatal arrhythmia;
* Asphyxia.
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Semmelweis University
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Dr. Gasparics Ákos
Chief Investigator, Assistant Lecturer
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Ákos Gasparics, MD.PhD
Role: PRINCIPAL_INVESTIGATOR
Semmelweis University, Department of Obstetrics and Gynecology
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Pediatric Center, Semmelweis University
Budapest, , Hungary
Department of Obstetrics and Gynecology, Semmelweis University
Budapest, , Hungary
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Leina Mahdi, MD
Role: primary
References
Explore related publications, articles, or registry entries linked to this study.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Informed Consent Form
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2022-003202-77
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
NEOKOFF22
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.