Hypoxia
Conditions
Keywords
Prematurity, Apnea of prematurity, Intermittent hypoxia
Brief summary
The purpose of this pilot study is to document the extent to which intermittent hypoxia persists beyond the age of discontinuing clinical methylxanthine, and will assess the effect of caffeine treatment on the number of intermittent hypoxia episodes and the total number of seconds with a hemoglobin oxygen saturation (HbO2 SAT) below 90%.
Detailed description
Infants with prior clinical treatment with caffeine in the neonatal intensive care unit (NICU) will be enrolled and continuous physiologic data recording of oxygen hemoglobin saturation (HbO2 SAT) and heart rate will begin as early as 33 weeks postmenstrual age (PMA). Randomization will occur when enrolled infants reach a corrected gestational age of at least 34 weeks PMA AND clinical caffeine has been discontinued for at least 5 days. Infants will be randomized to receive caffeine or to continue with usual care. The group randomized to start caffeine will receive an oral loading dose of caffeine citrate of 20 mg/kg on Day #1, followed by a single daily oral maintenance dose of 6 mg/kg starting on Day #2 and continued daily thereafter until 40 weeks PMA. The continuous oximeter recordings will be stopped at the same time. The number of intermittent hypoxia events/hour per week will be compared between the caffeine group and the usual care (no-caffeine) group for each week of physiologic data recordings.
Interventions
DRUGCaffeine citrate 6 mg/kg/day
Comparison of caffeine citrate 6 mg/kg/day versus no caffeine (usual care) on extent of intermittent hypoxia at 35, 36, 37, 38, 39, and 40 weeks postmenstrual age.
Sponsors
American SIDS Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
33 Weeks to 37 Weeks
Healthy volunteers
No
Inclusion criteria
1. Gestational age of 25 + 0 to 32 + 0 weeks PMA at birth, and 34 + 0 to 375 + 6 weeks PMA at randomization 2. Prior treatment with caffeine based on routine clinical indications, and clinical caffeine now discontinued ≥5 days before randomization 3. Previously tolerated clinical treatment with caffeine 4. Breathing room air (no current supplemental O2 treatment; may have previously required respiratory support) 5. Parental consent to enroll in pilot study
Exclusion criteria
1. Congenital syndrome or other medical diagnosis associated with known risk for neurodevelopmental abnormality, including intraventricular hemorrhage Grade 3 or greater, cyanotic congenital heart disease, confirmed central nervous system infection, or fetal alcohol syndrome 2. Currently receiving supplemental oxygen, ventilatory support, or nasal airflow therapy 3. Clinical decision to restart caffeine prior to completing 5 days of continuous physiologic monitoring after clinical caffeine stopped 4. Anticipated inability to meet protocol requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Episodes of Intermittent Hypoxia Per Hour | 35, 36, 37, 38 weeks postmenstrual age | Number of episodes of Intermittent hypoxia per hour of pulse oximeter recording less than 90% oxygen saturation |
| Number of Seconds of Intermittent Hypoxia Per Hour | 35, 36, 37, 38 weeks postmenstrual age | Number of seconds of Intermittent hypoxia per hour of pulse oximeter recording less than 90% oxygen saturation |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Caffeine Caffeine citrate 6 mg/kg/day
Caffeine citrate 6 mg/kg/day: Comparison of caffeine citrate 6 mg/kg/day versus no caffeine (usual care) on extent of intermittent hypoxia at 35, 36, 37, 38, 39, and 40 weeks postmenstrual age. | 45 |
| Active Comparator: no Caffeine Compare extended use of caffeine citrate 6 mg/kg/day to no caffeine (usual care) in regard to extent of intermittent hypoxia from 35 weeks postmenstrual age (PMA) to 40 weeks PMA. | 53 |
| Total | 98 |
Baseline characteristics
| Characteristic | Caffeine | Active Comparator: no Caffeine | Total |
|---|---|---|---|
| Age, Customized Gestational Age | 28.6 Weeks STANDARD_DEVIATION 1.7 | 29.1 Weeks STANDARD_DEVIATION 1.7 | 28.9 Weeks STANDARD_DEVIATION 1.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 8 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 45 Participants | 85 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Mean birth weight | 1262.1 grams STANDARD_DEVIATION 265.6 | 1274.5 grams STANDARD_DEVIATION 270.3 | 1270.1 grams STANDARD_DEVIATION 267.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 9 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 27 Participants | 42 Participants | 69 Participants |
| Region of Enrollment United States | 45 participants | 53 participants | 98 participants |
| Sex: Female, Male Female | 21 Participants | 26 Participants | 47 Participants |
| Sex: Female, Male Male | 24 Participants | 27 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 42 | 0 / 53 |
| serious Total, serious adverse events | 0 / 42 | 0 / 53 |
Outcome results
Primary
Episodes of Intermittent Hypoxia Per Hour
Number of episodes of Intermittent hypoxia per hour of pulse oximeter recording less than 90% oxygen saturation
Time frame: 35, 36, 37, 38 weeks postmenstrual age
Population: Intention to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Caffeine | Episodes of Intermittent Hypoxia Per Hour | Week 35 | 3.6 Events per hour | Standard Deviation 4.3 |
| Caffeine | Episodes of Intermittent Hypoxia Per Hour | Week 36 | 3.8 Events per hour | Standard Deviation 4.5 |
| Caffeine | Episodes of Intermittent Hypoxia Per Hour | Week 37 | 4.3 Events per hour | Standard Deviation 5.9 |
| Caffeine | Episodes of Intermittent Hypoxia Per Hour | Week 38 | 4.2 Events per hour | Standard Deviation 5.7 |
| Active Comparator: no Caffeine | Episodes of Intermittent Hypoxia Per Hour | Week 38 | 4.7 Events per hour | Standard Deviation 6.1 |
| Active Comparator: no Caffeine | Episodes of Intermittent Hypoxia Per Hour | Week 35 | 8.4 Events per hour | Standard Deviation 8.4 |
| Active Comparator: no Caffeine | Episodes of Intermittent Hypoxia Per Hour | Week 37 | 5.2 Events per hour | Standard Deviation 6.8 |
| Active Comparator: no Caffeine | Episodes of Intermittent Hypoxia Per Hour | Week 36 | 8.2 Events per hour | Standard Deviation 11.5 |
Comparison: \>80% probability of detecting at least a 36% reduction in intermittent hypoxia events/hour of recording and in sec/hour \<90% oxygen saturation/hour of recordingp-value: <0.05GEE gamma regression models
Primary
Number of Seconds of Intermittent Hypoxia Per Hour
Number of seconds of Intermittent hypoxia per hour of pulse oximeter recording less than 90% oxygen saturation
Time frame: 35, 36, 37, 38 weeks postmenstrual age
Population: Intention to treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Caffeine | Number of Seconds of Intermittent Hypoxia Per Hour | Week 37 | 58.8 seconds per hour | Standard Deviation 74.1 |
| Caffeine | Number of Seconds of Intermittent Hypoxia Per Hour | Week 36 | 49.5 seconds per hour | Standard Deviation 52.1 |
| Caffeine | Number of Seconds of Intermittent Hypoxia Per Hour | Week 38 | 69.3 seconds per hour | Standard Deviation 108.8 |
| Caffeine | Number of Seconds of Intermittent Hypoxia Per Hour | Week 35 | 50.9 seconds per hour | Standard Deviation 48.1 |
| Active Comparator: no Caffeine | Number of Seconds of Intermittent Hypoxia Per Hour | Week 38 | 66.0 seconds per hour | Standard Deviation 74.8 |
| Active Comparator: no Caffeine | Number of Seconds of Intermittent Hypoxia Per Hour | Week 36 | 100.1 seconds per hour | Standard Deviation 114.6 |
| Active Comparator: no Caffeine | Number of Seconds of Intermittent Hypoxia Per Hour | Week 37 | 66.8 seconds per hour | Standard Deviation 75.2 |
| Active Comparator: no Caffeine | Number of Seconds of Intermittent Hypoxia Per Hour | Week 35 | 106.3 seconds per hour | Standard Deviation 89 |