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

NCT06401083 | Recruiting Phase 4

• 2 other identifiers: NEOKOFF222022-003202-77
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Apnea of Prematurity; Premature Birth; Respiratory Failure

Keywords

prematurity; caffeine; methylxanthine; apnea of prematurity; extubation failure

Outcome Measures

Primary Outcomes (1)

• Rate of extubation failure

  Reintubation. The discretion of the attending physician.

  48 hours

Secondary Outcomes (18)

• Frequency of apneas

  48 hours

• Change in the mean heart rate

  72 hours

• Tachycardia

  72 hours

• Volume of gastric residuals

  72 hours

• Reduction/Cessation of feeding

  48hours

Study Arms (2)

Pre-extubational caffeine-citrate

ACTIVE COMPARATOR

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.

Drug: Caffeine citrate

Routine care

NO INTERVENTION

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.

Interventions

Caffeine citrate DRUG

20 mg/kg caffeine-citrate before the planned extubation.

Also known as: CITRATE DE CAFEINE COOPER 25 mg/ml Coopération Pharmaceutique Française, Melun, France

Pre-extubational caffeine-citrate

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Premature infant born before 32nd week of gestation is completed;
• Had been mechanically ventilated for at least 48 hours;
• Before the first planned extubation.

You may not qualify if:

• Lack of informed consent, refusal to participate in the study;
• Major congenital anomaly;
• Had not received surfactant treatment;
• Hydrops foetalis;
• Persistent tachycardia before extubation, fetal/neonatal arrhythmia;
• Asphyxia.

Sponsors & Collaborators

• Semmelweis University: lead

Study Sites (2)

Pediatric Center, Semmelweis University

Budapest, 1083, Hungary

RECRUITING

Department of Obstetrics and Gynecology, Semmelweis University

Budapest, 1088, Hungary

RECRUITING

Related Publications (13)

• 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.

  PMID: 33712716 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.

  PMID: 32215452 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.

  PMID: 24931325 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.

  PMID: 16707748 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.

  PMID: 17989382 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.

  PMID: 33214064 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.

  PMID: 32154294 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.

  PMID: 30671477 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.

  PMID: 25644724 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.

  PMID: 25856169 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.

  PMID: 35691280 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.

  PMID: 34381359 BACKGROUND

• 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.

  PMID: 39804861 DERIVED

MeSH Terms

Conditions

Apnea; Premature Birth; Respiratory Insufficiency

Interventions

caffeine citrate

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Ákos Gasparics, MD.PhD

  Semmelweis University, Department of Obstetrics and Gynecology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kinga Kovács, MD.

CONTACT

+36206663718; kovacs.kinga1@semmelweis.hu

Ákos Gasparics, MD.PhD

CONTACT

+36206663684; gasparics.akos@semmelweis.hu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator, Assistant Lecturer

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: May 6, 2024
• Study Start: December 21, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 6, 2024

Record last verified: 2024-04

Locations

HU (2)