Apnea of PrematurityPhase 4NEOKOFF22NCT06401083
The Effect of an Additional Pre-extubational Loading Dose of Caffeine-citrate
A Phase 4 study testing Caffeine citrate in people with Apnea of Prematurity and Premature Birth, run by Semmelweis University at 2 sites in Hungary.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Apnea of Prematurity, Premature Birth, Respiratory Failure
- What is being tested?
- Caffeine citrate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 226 participants
- Where
- 2 sitesHungary
- Study dates
- 21 Dec 2023to Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Premature infant born before 32nd week of gestation is completed;
- Had been mechanically ventilated for at least 48 hours;
- Before the first planned extubation.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Hungary2 sites, 2 recruiting
- Recruiting
Pediatric Center, Semmelweis University
Budapest, 1083
Leina Mahdi, MD
- Recruiting
Department of Obstetrics and Gynecology, Semmelweis University
Budapest, 1088
Kinga Kovács, MD, +36206663718, kovacs.kinga1@semmelwies.hu
About this study
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.
Read the detailed description
The most common cause of the failure of non-invasive ventilatory support is poor spontaneous respiratory activity in preterm infants and recurrent respiratory arrest (apnea) due to the immature nervous system. The national and international literature has extensively studied apnea in preterm infants. Apnea is a respiratory failure of 15-20 seconds or shorter duration associated with bradycardia or desaturation. Apneas develop in preterm infants due to prematurity of the respiratory center and chemoreceptors and reduced patency of the upper airway. Apnea in preterm infants is the most common indication for intubation and reintubation.
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
- Apnea of Prematurity, Premature Birth, Respiratory Failure
- Being tested
- Caffeine citrate
- Keywords
- prematurity, caffeine, methylxanthine, apnea of prematurity, extubation failure
- Medical subject headings
- Apnea, Premature Birth, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Caffeine citrateDrug
Also called CITRATE DE CAFEINE COOPER 25 mg/ml Coopération Pharmaceutique Française, Melun, France
20 mg/kg caffeine-citrate before the planned extubation.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of extubation failure
Reintubation. The discretion of the attending physician.
Measured: 48 hours
Secondary outcomes (18)
Frequency of apneas
Respiratory failure of 15-20 seconds or shorter duration associated with bradycardia or desaturation.
Measured: 48 hours
Change in the mean heart rate
Mean heart rate measured 24 hours before and 48 hours after intervention.
Measured: 72 hours
Tachycardia
The time interval when the heart rate >200 (min) during one day (1440 min) in percentage.
Measured: 72 hours
Volume of gastric residuals
Gastric residuals measured 24 hours before and 48 hours after intervention.
Measured: 72 hours
Reduction/Cessation of feeding
48 hours after intervention.
Measured: 48hours
Change in mean arterial blood pressure
Mean blood pressure measured 24 hours before and after intervention measured with non-invasive methods.
Measured: 48 hours
Mechanical ventilation (MV) days
MV days during the length of hospital stay
Measured: At discharge from participating centres, an average of one month.
Non-invasive ventilation (NIV) days
NIV days during the length of hospital stay
Measured: At discharge from participating centres, an average of one month.
Rate of necrotizing enterocolitis
Development of necrotizing enterocolitis according to Bell stages.
Measured: At discharge from participating centres, an average of one month.
Rate of Intraventricular hemorrhage
Development or progression of intraventricular hemorrhage according to Papile stages diagnosed with cranial ultrasound.
Measured: At discharge from participating centres, an average of one month.
Rate of periventricular leukomalacia
Development of periventricular leukomalacia, seen on cranial ultrasound.
Measured: At discharge from participating centres, an average of one month.
Rate of late-onset sepsis
Culture proven sepsis after the first 72 hours of life.
Measured: At discharge from participating centres, an average of one month.
Rate of patent ductus arteriosus
Pharmacological or surgical treatment was required.
Measured: At discharge from participating centres, an average of one month.
Rate of bronchopulmonary dysplasia
Diagnosis of bronchopulmonary dysplasia.
Measured: 36th postmenstrual age
Rate of death before discharge
Measured: At discharge from participating centres, an average of one month.
Required oxygen concentration
Required oxygen concentration before and after the intervention.
Measured: 24 hours
Long term neurodevelopmental outcome
Measured by Bayley score. The standardized mean score is 100 (SD 15), with scores lower than 85 indicating mild impairment, and lower than 70 indicating moderate or severe impairment.
Measured: At 2 years of corrected age
Severity of sensoric or motoric impairment
Hearing or visual impairment, and cerebral palsy
Measured: At 2 years of corrected age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2024
- Study start21 Dec 2023
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Apnea of PrematurityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 226 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Semmelweis University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Gasparics Ákos, Semmelweis University
- Investigators
- Ákos Gasparics, MD.PhD, Principal investigator, Semmelweis University, Department of Obstetrics and Gynecology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06401083
- Sponsor's protocol ID
- NEOKOFF22
- Other IDs
- 2022-003202-77
- Acronym
- NEOKOFF22
- Status last verified
- Apr 2024
- First submitted
- 18 Mar 2024
- Last updated
- 6 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 33712716Bacci 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.
PubMed 32215452Kreutzer 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.
PubMed 24931325Schmidt 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.
PubMed 16707748Schmidt 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.
PubMed 17989382Eichenwald 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.
PubMed 33214064Moschino 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.
PubMed 32154294Chen 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.
PubMed 30671477Mohammed 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.
PubMed 25644724McPherson 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.
PubMed 25856169Chavez 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.
PubMed 35691280Long 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.
PubMed 34381359Kovacs 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.
PubMed 39804861
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of an Additional Pre-extubational Loading Dose of Caffeine-citrate
- ClinicalTrials.gov ID
- NCT06401083
- Acronym / sponsor ID
- NEOKOFF22 / NEOKOFF22
- Conditions
- Apnea of Prematurity, Premature Birth, Respiratory Failure
- Keywords
- prematurity, caffeine, methylxanthine, apnea of prematurity, extubation failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 226 participants (estimated)
- Lead sponsor
- Semmelweis UniversityUniversity, hospital or other
- Study start
- 21 Dec 2023 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 6 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The most common cause of the failure of non-invasive ventilatory support is poor spontaneous respiratory activity in preterm infants and recurrent respiratory arrest (apnea) due to the immature nervous system. The national and international literature has extensively studied apnea in preterm infants. Apnea is a respiratory failure of 15-20 seconds or shorter duration associated with bradycardia or desaturation. Apneas develop in preterm infants due to prematurity of the respiratory center and chemoreceptors and reduced patency of the upper airway. Apnea in preterm infants is the most common indication for intubation and reintubation.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pre-extubational caffeine-citrate | Active comparator | Drug: Caffeine citrateParticipants 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. |
| 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Premature infant born before 32nd week of gestation is completed;
- Had been mechanically ventilated for at least 48 hours;
- Before the first planned extubation.
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Caffeine citrateAlso: CITRATE DE CAFEINE COOPER 25 mg/ml Coopération Pharmaceutique Française, Melun, France20 mg/kg caffeine-citrate before the planned extubation. | Drug | Pre-extubational caffeine-citrate |
Primary outcome
Rate of extubation failure
Time frame: 48 hours
Reintubation. The discretion of the attending physician.
18 secondary outcomes
Frequency of apneas
Time frame: 48 hours
Change in the mean heart rate
Time frame: 72 hours
Tachycardia
Time frame: 72 hours
Volume of gastric residuals
Time frame: 72 hours
Reduction/Cessation of feeding
Time frame: 48hours
Change in mean arterial blood pressure
Time frame: 48 hours
Mechanical ventilation (MV) days
Time frame: At discharge from participating centres, an average of one month.
Non-invasive ventilation (NIV) days
Time frame: At discharge from participating centres, an average of one month.
Rate of necrotizing enterocolitis
Time frame: At discharge from participating centres, an average of one month.
Rate of Intraventricular hemorrhage
Time frame: At discharge from participating centres, an average of one month.
Rate of periventricular leukomalacia
Time frame: At discharge from participating centres, an average of one month.
Rate of late-onset sepsis
Time frame: At discharge from participating centres, an average of one month.
Rate of patent ductus arteriosus
Time frame: At discharge from participating centres, an average of one month.
Rate of bronchopulmonary dysplasia
Time frame: 36th postmenstrual age
Rate of death before discharge
Time frame: At discharge from participating centres, an average of one month.
Required oxygen concentration
Time frame: 24 hours
Long term neurodevelopmental outcome
Time frame: At 2 years of corrected age
Severity of sensoric or motoric impairment
Time frame: At 2 years of corrected age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2024.
- Background: PubMed 33712716Erickson 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: PubMed 32215452Bacci 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: PubMed 24931325Kreutzer 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: PubMed 16707748Schmidt 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: PubMed 17989382Schmidt 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: PubMed 33214064Eichenwald 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: PubMed 32154294Moschino 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: PubMed 30671477Chen 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: PubMed 25644724Mohammed 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: PubMed 25856169McPherson 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: PubMed 35691280Chavez 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: PubMed 34381359Long 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ákos Gasparics, MD.PhD principal investigator
Semmelweis University, Department of Obstetrics and Gynecology
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Caffeine citrate in people with Apnea of Prematurity and Premature Birth, run by Semmelweis University at 2 sites in Hungary.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kinga Kovács, MD. (+36206663718, kovacs.kinga1@semmelweis.hu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of extubation failure (time frame: 48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06401083, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2024.