Trial Outcomes & Findings for Caffeine to Reduce Mechanical Ventilation in Preterm Infants (NCT NCT01751724)

Results Overview

Defined as age of extubation with infant remaining extubated for more than 24 hours.

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

87 participants

Primary outcome timeframe

From birth to until 36 weeks postmenstrual age

Results posted on

2017-06-19

Participant Flow

Recruitment was conducted at the Holtz Children's Hospital newborn intensive care unit of Jackson Health System/University of Miami Medical Center from January 2013 to October 2015.

87 infants were enrolled. Of these, 1 died before randomization. 86 infants were randomized and assigned an intervention arm.

Participant milestones

Participant milestones
Measure	Caffeine Arm Subjects randomized to this arm will receive blinded Caffeine citrate. Caffeine citrate: 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.	Placebo Arm Subjects randomized to this arm will receive blinded Placebo (equivalent volume of normal saline). Normal saline: 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.
Overall Study STARTED	42	44
Overall Study COMPLETED	41	42
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Caffeine Arm Subjects randomized to this arm will receive blinded Caffeine citrate. Caffeine citrate: 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.	Placebo Arm Subjects randomized to this arm will receive blinded Placebo (equivalent volume of normal saline). Normal saline: 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.
Overall Study extubated bef.start assigned treatment	1	0
Overall Study withdrawn by parent	0	2

Baseline Characteristics

Caffeine to Reduce Mechanical Ventilation in Preterm Infants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Caffeine Arm n=41 Participants Subjects randomized to this arm will receive blinded Caffeine citrate. Caffeine citrate: 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.	Placebo Arm n=42 Participants Subjects randomized to this arm will receive blinded Placebo (equivalent volume of normal saline). Normal saline: 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.	Total n=83 Participants Total of all reporting groups
Age, Continuous	48 hours STANDARD_DEVIATION 25 • n=5 Participants	49 hours STANDARD_DEVIATION 31 • n=7 Participants	48 hours STANDARD_DEVIATION 28 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	25 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	17 Participants n=7 Participants	47 Participants n=5 Participants
Race/Ethnicity, Customized Black race	19 Participants n=5 Participants	21 Participants n=7 Participants	40 Participants n=5 Participants
Gestational age	25.7 weeks n=5 Participants	26.1 weeks n=7 Participants	25.9 weeks n=5 Participants
Birth weight	670 grams n=5 Participants	720 grams n=7 Participants	700 grams n=5 Participants
Fraction of inspired oxygen at enrollment	0.25 oxygen fraction n=5 Participants	0.23 oxygen fraction n=7 Participants	.24 oxygen fraction n=5 Participants
Mean airway pressure at enrollment	9 centimeters of water n=5 Participants	8 centimeters of water n=7 Participants	9 centimeters of water n=5 Participants

PRIMARY outcome

Timeframe: From birth to until 36 weeks postmenstrual age

Defined as age of extubation with infant remaining extubated for more than 24 hours.

Outcome measures

Outcome measures
Measure	Caffeine Arm n=41 Participants Subjects randomized to this arm will receive blinded Caffeine citrate. Caffeine citrate: 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.	Placebo Arm n=42 Participants Subjects randomized to this arm will receive blinded Placebo (equivalent volume of normal saline). Normal saline: 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.
Age at First Successful Extubation	24 days Interval 9.5 to 41.0	20 days Interval 9.3 to 43.0

SECONDARY outcome

Timeframe: From the time of randomization up to 36 weeks corrected age, or until the time of discharge or death

Outcome measures

Outcome measures
Measure	Caffeine Arm n=41 Participants Subjects randomized to this arm will receive blinded Caffeine citrate. Caffeine citrate: 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.	Placebo Arm n=42 Participants Subjects randomized to this arm will receive blinded Placebo (equivalent volume of normal saline). Normal saline: 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.
Survival	32 Participants	37 Participants

SECONDARY outcome

Timeframe: From the time of first intubation until the last extubation, up to 36 weeks corrected age

Population: Infants alive at 36 weeks postmenstrual age

Outcome measures

Outcome measures
Measure	Caffeine Arm n=32 Participants Subjects randomized to this arm will receive blinded Caffeine citrate. Caffeine citrate: 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.	Placebo Arm n=37 Participants Subjects randomized to this arm will receive blinded Placebo (equivalent volume of normal saline). Normal saline: 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.
Total Duration of Mechanical Ventilation	32 days Interval 11.0 to 43.0	26 days Interval 10.0 to 44.0

SECONDARY outcome

Timeframe: From the time of first initiation until the last day of oxygen supplementation, up to 36 weeks corrected age

Population: Infants alive at 36 weeks postmenstrual age

Outcome measures

Outcome measures
Measure	Caffeine Arm n=32 Participants Subjects randomized to this arm will receive blinded Caffeine citrate. Caffeine citrate: 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.	Placebo Arm n=37 Participants Subjects randomized to this arm will receive blinded Placebo (equivalent volume of normal saline). Normal saline: 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.
Total Duration of Oxygen Supplementation	55 days Interval 31.0 to 86.0	59 days Interval 36.0 to 106.0

SECONDARY outcome

Timeframe: Evaluated at 36 weeks corrected postmenstrual age

Population: Infants alive at 36 weeks postmenstrual age

BPD defined as need for oxygen for at least 28 days and at 36 weeks post-menstrual age.

Outcome measures

Outcome measures
Measure	Caffeine Arm n=32 Participants Subjects randomized to this arm will receive blinded Caffeine citrate. Caffeine citrate: 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.	Placebo Arm n=37 Participants Subjects randomized to this arm will receive blinded Placebo (equivalent volume of normal saline). Normal saline: 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.
Number of Infants With Bronchopulmonary Dysplasia (BPD)	15 Participants	20 Participants

SECONDARY outcome

Timeframe: From the time of randomization until 36 weeks corrected age, discharge or death

Discharge alive without BPD. BPD defined as need for oxygen for at least 28 days and at 36 weeks post-menstrual age.