PrematurityNCT01751724
Caffeine to Reduce Mechanical Ventilation in Preterm Infants
A study testing Caffeine citrate and Normal saline in people with Prematurity and Apnea, run by University of Miami at 1 site in United States.
Trial summary
Most premature infants require mechanical ventilation for prolonged periods of time and a significant proportion of them develop Bronchopulmonary Dysplasia (BPD). Caffeine is a stimulant of the respiratory center and has been used for the treatment of Apnea of Prematurity in infants not requiring mechanical… Read more about this study
- Who is it for?
- Ages 1 day to 5 days
- Conditions the study is for
- Prematurity, Apnea, Respiratory Failure
- What is being tested?
- Caffeine citrate and Normal saline
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 87 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2012to Jan 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 day to 5 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Premature neonates born between 23 and 30 completed weeks of gestation.
- Requiring mechanical ventilation within the first 5 postnatal days
- Written-informed parental consent for the study
Who cannot join
- Major congenital anomalies
- Small for gestational age
Trial locations and contacts
1 site in 1 country.
United States1 site
NICU, Holtz Children's Hospital, Jackson Health System
Miami, Florida, 33136
About this study
Official title: Use of Caffeine to Reduce Length of Mechanical Ventilation in Preterm Infants
Most premature infants require mechanical ventilation for prolonged periods of time and a significant proportion of them develop Bronchopulmonary Dysplasia (BPD). Caffeine is a stimulant of the respiratory center and has been used for the treatment of Apnea of Prematurity in infants not requiring mechanical ventilation or to facilitate weaning from mechanical ventilation by starting therapy shortly before extubation. Recently the use of Caffeine in ventilated infants has been initiated earlier because of the reported reduction in BPD. However there is paucity of data supporting this practice.
Because protracted mechanical ventilation and supplemental oxygen increase the risk of developing BPD, a therapy that would facilitate the reduction of the respiratory support and shorten its duration is desirable. Therefore, it is of importance to evaluate the effects of early Caffeine initiation and administration during the course of mechanical ventilation in preterm infants by means of a randomized placebo-controlled trial.
Read more
Hypothesis:
The primary hypothesis of this study is that early use of caffeine in mechanically ventilated preterm infants will reduce the time to first elective extubation and secondarily, that this will reduce the total duration of mechanical ventilation and oxygen supplementation, and reduce the incidence and severity of BPD.
Objective:
The objective of this trial is to evaluate the effects of early caffeine use during mechanical ventilation on the time to first elective extubation, total duration of mechanical ventilation and oxygen supplementation, and the incidence of BPD.
Study Design:
This will be a single-center prospective, randomized, double-blind, placebo controlled clinical trial.
Population:
Premature neonates born between 23 and 30 completed weeks of gestation, who require mechanical ventilation within the first 5 days of life will be enrolled. Infants with major congenital anomalies or small for gestational age will be excluded.
Methods:
Infants will be randomized within the first 5 days to receive a study drug consisting of either blinded Caffeine citrate or blinded Placebo (equivalent volume of normal saline). Infants will continue to receive the study drug until the first elective extubation.
- Conditions
- Prematurity, Apnea, Respiratory Failure
- Being tested
- Caffeine citrate, Normal saline
- Keywords
- Premature infants, Caffeine, Methylxanthines, Mechanical ventilation, Oxygen, Weaning, Bronchopulmonary dysplasia
- Medical subject headings
- Premature Birth, Apnea, Respiratory Insufficiency, Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Caffeine citrateDrug
Enrolled subjects will be randomized to receive a study drug consisting of either blinded Caffeine citrate.
Randomization and study drug preparation will be done by the NICU pharmacy. Investigators and clinicians will be blinded to the assigned drug.
After randomization, an initial loading dose of 20 mg/Kg of study drug will be followed by a 5 mg/Kg/day maintenance dose. The assigned study drug will be administered intravenous or orally as determined by the clinical team.
Infants will continue to receive the study drug until 12 hours prior to the first elective extubation.
Normal salineOther
Enrolled subjects will be randomized to receive a study drug consisting of blinded Placebo (equivalent volume of normal saline).
Randomization and study drug preparation will be done by the NICU pharmacy. Investigators and clinicians will be blinded to the assigned drug.
After randomization, an initial loading dose of 20 mg/Kg of study drug will be followed by a 5 mg/Kg/day maintenance dose. The assigned study drug will be administered intravenous or orally as determined by the clinical team.
Infants will continue to receive the study drug until 12 hours prior to the first elective extubation.
| Study group | Role | What they receive |
|---|---|---|
| Caffeine Arm | Experimental | Subjects randomized to this arm will receive blinded Caffeine citrate. Receives: Drug: Caffeine citrate |
| Placebo Arm | Placebo comparator | Subjects randomized to this arm will receive blinded Placebo (equivalent volume of normal saline). Receives: Other: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Age at First Successful Extubation
Defined as age of extubation with infant remaining extubated for more than 24 hours.
Measured: From birth to until 36 weeks postmenstrual age
Secondary outcomes (5)
Survival
Measured: From the time of randomization up to 36 weeks corrected age, or until the time of discharge or death
Total Duration of Mechanical Ventilation
Measured: From the time of first intubation until the last extubation, up to 36 weeks corrected age
Total Duration of Oxygen Supplementation
Measured: From the time of first initiation until the last day of oxygen supplementation, up to 36 weeks corrected age
Number of Infants With Bronchopulmonary Dysplasia (BPD)
BPD defined as need for oxygen for at least 28 days and at 36 weeks post-menstrual age.
Measured: Evaluated at 36 weeks corrected postmenstrual age
Survival Without BPD
Discharge alive without BPD. BPD defined as need for oxygen for at least 28 days and at 36 weeks post-menstrual age.
Measured: From the time of randomization until 36 weeks corrected age, discharge or death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2012 (estimated)
- Study startDec 2012
- Primary completionJan 2016
- Study completionJan 2016
Why it stopped: Safety
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eduardo Bancalari, University of Miami
- Investigators
- Eduardo Bancalari, M.D., Principal investigator, University of MiamiNelson Claure, M.Sc., Ph.D., Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01751724
- Sponsor's protocol ID
- 20120786
- Status last verified
- May 2017
- First submitted
- 12 Dec 2012
- Last updated
- 19 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Amaro CM, Bello JA, Jain D, Ramnath A, D'Ugard C, Vanbuskirk S, Bancalari E, Claure N. Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants: A Randomized, Placebo-Controlled Trial. J Pediatr. 2018 May;196:52-57. doi: 10.1016/j.jpeds.2018.01.010. Epub 2018 Mar 6.
PubMed 29519541
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Caffeine to Reduce Length of Mechanical Ventilation in Preterm Infants
- ClinicalTrials.gov ID
- NCT01751724
- Acronym / sponsor ID
- 20120786
- Conditions
- Prematurity, Apnea, Respiratory Failure
- Keywords
- Premature infants, Caffeine, Methylxanthines, Mechanical ventilation, Oxygen, Weaning, Bronchopulmonary dysplasia
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Safety
- Enrolment
- 87 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 18 Dec 2012 (estimated)
- Results
- Posted 19 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Most premature infants require mechanical ventilation for prolonged periods of time and a significant proportion of them develop Bronchopulmonary Dysplasia (BPD). Caffeine is a stimulant of the respiratory center and has been used for the treatment of Apnea of Prematurity in infants not requiring mechanical ventilation or to facilitate weaning from mechanical ventilation by starting therapy shortly before extubation. Recently the use of Caffeine in ventilated infants has been initiated earlier because of the reported reduction in BPD. However there is paucity of data supporting this practice.
Because protracted mechanical ventilation and supplemental oxygen increase the risk of developing BPD, a therapy that would facilitate the reduction of the respiratory support and shorten its duration is desirable. Therefore, it is of importance to evaluate the effects of early Caffeine initiation and administration during the course of mechanical ventilation in preterm infants by means of a randomized placebo-controlled trial.
Hypothesis:
The primary hypothesis of this study is that early use of caffeine in mechanically ventilated preterm infants will reduce the time to first elective extubation and secondarily, that this will reduce the total duration of mechanical ventilation and oxygen supplementation, and reduce the incidence and severity of BPD.
Objective:
The objective of this trial is to evaluate the effects of early caffeine use during mechanical ventilation on the time to first elective extubation, total duration of mechanical ventilation and oxygen supplementation, and the incidence of BPD.
Study Design:
This will be a single-center prospective, randomized, double-blind, placebo controlled clinical trial.
Population:
Premature neonates born between 23 and 30 completed weeks of gestation, who require mechanical ventilation within the first 5 days of life will be enrolled. Infants with major congenital anomalies or small for gestational age will be excluded.
Methods:
Infants will be randomized within the first 5 days to receive a study drug consisting of either blinded Caffeine citrate or blinded Placebo (equivalent volume of normal saline). Infants will continue to receive the study drug until the first elective extubation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Caffeine Arm | Experimental | Drug: Caffeine citrateSubjects randomized to this arm will receive blinded Caffeine citrate. |
| Placebo Arm | Placebo comparator | Other: Normal salineSubjects randomized to this arm will receive blinded Placebo (equivalent volume of normal saline). |
Who may qualify
- Ages
- 1 day to 5 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Premature neonates born between 23 and 30 completed weeks of gestation.
- Requiring mechanical ventilation within the first 5 postnatal days
- Written-informed parental consent for the study
Key exclusion criteria (2 listed)
- Major congenital anomalies
- Small for gestational age
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 citrateEnrolled subjects will be randomized to receive a study drug consisting of either blinded Caffeine citrate. Randomization and study drug preparation will be done by the NICU pharmacy. Investigators and clinicians will be blinded to the assigned drug. After randomization, an initial loading dose of 20 mg/Kg of study drug will be followed by a 5 mg/Kg/day maintenance dose. The assigned study drug will be administered intravenous or orally as determined by the clinical team. Infants will continue to receive the study drug until 12 hours prior to the first elective extubation. | Drug | Caffeine Arm |
| Normal salineEnrolled subjects will be randomized to receive a study drug consisting of blinded Placebo (equivalent volume of normal saline). Randomization and study drug preparation will be done by the NICU pharmacy. Investigators and clinicians will be blinded to the assigned drug. After randomization, an initial loading dose of 20 mg/Kg of study drug will be followed by a 5 mg/Kg/day maintenance dose. The assigned study drug will be administered intravenous or orally as determined by the clinical team. Infants will continue to receive the study drug until 12 hours prior to the first elective extubation. | Other | Placebo Arm |
Primary outcome
Age at First Successful Extubation
Time frame: From birth to until 36 weeks postmenstrual age
Defined as age of extubation with infant remaining extubated for more than 24 hours.
5 secondary outcomes
Survival
Time frame: From the time of randomization up to 36 weeks corrected age, or until the time of discharge or death
Total Duration of Mechanical Ventilation
Time frame: From the time of first intubation until the last extubation, up to 36 weeks corrected age
Total Duration of Oxygen Supplementation
Time frame: From the time of first initiation until the last day of oxygen supplementation, up to 36 weeks corrected age
Number of Infants With Bronchopulmonary Dysplasia (BPD)
Time frame: Evaluated at 36 weeks corrected postmenstrual age
Survival Without BPD
Time frame: From the time of randomization until 36 weeks corrected age, discharge or death
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29519541Amaro CM, Bello JA, Jain D, Ramnath A, D'Ugard C, Vanbuskirk S, Bancalari E, Claure N. Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants: A Randomized, Placebo-Controlled Trial. J Pediatr. 2018 May;196:52-57. doi: 10.1016/j.jpeds.2018.01.010. Epub 2018 Mar 6.
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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. This study is not recruiting at the moment.
Eduardo Bancalari, M.D. principal investigator
University of Miami
Nelson Claure, M.Sc., Ph.D. principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Caffeine citrate and Normal saline in people with Prematurity and Apnea, run by University of Miami at 1 site in United States.
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 2 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: stopped early, as of the sponsor's last update on 19 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Age at First Successful Extubation (time frame: From birth to until 36 weeks postmenstrual age). 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 NCT01751724, which also lists 1 linked publication.
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 19 Jun 2017.