Apnea of Prematurity
Conditions
Keywords
Feeding, Caffeine
Brief summary
This study aims to assess whether extending the duration of caffeine therapy will help preterm infants achieve full oral feeding faster.
Detailed description
This study is a randomized, double-blinded, placebo-controlled trial. Infants will be randomized to receive either caffeine or placebo for up to maximum of four additional weeks after meeting clinical criteria to discontinue caffeine. Initiation of oral feeding will be based on standard of care as determined by a neonatal occupational therapist and clinical cues. Oral feedings will be advanced by a standardized 5 step oral feeding protocol. The time it takes to achieve full oral feeds between the treatment and control groups will be compared.
Interventions
DRUGCaffeine
Infants randomized to receive caffeine will continue to receive caffeine at the current weight-based dose (which is the standard of care maintenance dose of 10-15 mg/kg/day) given every 24 hours. The weight-based dose calculated using the weight at the time of enrollment will be the weight-based dose used for the duration of the study. The dose will be weight adjusted every 7 days, starting on the day of enrollment. Caffeine will be given enterally, via nasogastric tube or by mouth. The study drug (caffeine) will be administered for a maximum of 4 weeks. The study drug will be discontinued after 4 weeks or when the infant reaches Step 4 of our institution's oral feeding protocol (oral feeding 6 times per day), whichever comes first. The study drug will also be discontinued if the open-label maintenance caffeine is started by the clinical team based on clinical indications.
OTHERSterile Water Placebo
Infants randomized to the placebo group will be given sterile water at an equivalent volume to the volume if caffeine were to be given, using the previous weight-based caffeine dose. The placebo will be given every 24 hours. The dose/volume will be weight adjusted every 7 days, starting on the day of enrollment. The placebo will be given enterally, via nasogastric tube or by mouth. The placebo will be administered for a maximum of 4 weeks. The placebo will be discontinued after 4 weeks or when the infant reaches Step 4 of our institution's oral feeding protocol (oral feeding 6 times per day), whichever comes first. The placebo will also be discontinued if the open-label maintenance caffeine is started by the clinical team based on clinical indications.
Sponsors
University of California, Irvine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Families, nurses, therapists, and doctors will be blinded. Only pharmacy will be unblinded and know which subjects are in each treatment arm.
Intervention model description
This is a randomized, double-blinded, placebo-controlled trial of 40 preterm infants born at less than or equal to 32 weeks and 0 days gestation. Infants will be randomized to receive either caffeine or placebo for up to maximum of additional four (4) weeks after meeting clinical criteria to come off caffeine.
Eligibility
Sex/Gender
ALL
Age
1 Weeks to 40 Weeks
Healthy volunteers
No
Inclusion criteria
• Infants born at equal to or less than 32 weeks and 0 days gestational age AND * Equal to or greater than 34 weeks and 0 days corrected gestation at time of enrollment. * Off respiratory support for at least 2 days (nasal canula oxygen, high flow nasal canula, continuous positive airway pressure (CPAP), mechanical ventilation). * On caffeine and meet criteria to discontinue caffeine. * No significant cardiopulmonary events for at least 5 days (apnea \> 20 seconds, apnea with heart rate (HR) \< 80 beats per minute (bpm), HR \< 80 bpm with desaturation \< 85% or color change).
Exclusion criteria
* Infants with critical congenital heart disease. * Infants with neuromuscular conditions affecting respiration. * Infants with overt brain injury (i.e. severe Grade 3-4 intraventricular hemorrhage, cystic periventricular leukomalacia) that may affect oral feeding. * Infants with major genetic disorders. * Infants with anatomic anomalies that will hinder oral feeding. * Infants who have already progressed to Step 3 (of 5) of our institution's oral feeding protocol (oral feeds 4 times per day). * Infants who develop necrotizing enterocolitis after enrollment. * Failure to obtain consent or declined by parents.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to full feeds | From first nutritive oral feed until full oral feeds achieved, up to 6 weeks | The primary outcome is time (in days) to full oral bottle feeding or breastfeeding or a combination of both. Full oral bottle feeding is defined as 48 hours of consistent intake of at least 150ml/kg/day of formula or breastmilk. If the subject is on combination of bottle and breastfeeding, two consecutive days of positive weight gain will be used in place of 150ml/kg/day as primary outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to discharge | Randomization until discharge, up to 6 weeks | Time to discharge measured in days of hospitalization after randomization |
| Post menstrual age (PMA) at time of discharge | Randomization until discharge, up to 6 weeks | Post menstrual age at discharge |
| Number of significant cardiopulmonary events | Randomization until discharge, up to 6 weeks | Number of significant cardiopulmonary events defined as apnea \> 20 seconds, apnea with heart rate (HR) \< 80 beats per minute (bpm), HR \< 80 bpm with desaturation \< 85% or color change. Significant events are ones that occur while infant is asleep or lying down. |
| Weight change | Randomization until discharge, up to 6 weeks | Weight change measured by change in grams |
Countries
United States
Outcome results
None listed