The objective of this study is to evaluate the effect of continuing treatment with caffeine citrate in the hospital and at home in moderately preterm infants with resolved apnea of prematurity on days of hospitalization after randomization.
Study subjects will be patients in the NICU at one of the participating hospitals at a Neonatal Research Network site. Infants who meet the eligibility criteria will be randomized to either caffeine citrate at 10 mg/kg/dose or placebo (equal volume of all the excipients except for the active ingredient, caffeine citrate) to be given daily beginning within 72 hours of open label caffeine discontinuation. The infant may still require hospitalization for observation after discontinuation of open label caffeine or for other discharge issues such as temperature control or feeding tolerance. Once deemed ready for discharge, infants will be continued at home on the same dose of caffeine citrate or placebo for the first 28 days after hospital discharge. On the day of discharge, the parent will be supplied with 28 numbered vials with oral caffeine citrate (intervention group) or placebo at an equivalent volume (placebo group). The parents will be educated by the research nurse, discharge nurse, physician, or pharmacist on storage and administration of study medication. A member of the research team will contact the parents to obtain post-discharge information within 72 hours after discharge, once a week for the first 4 weeks, and biweekly during the weeks 5 to 8 after discharge.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
827
The study intervention is caffeine citrate given once daily at 10 mg/kg/day. It is given orally, before hospital discharge and 28 days after discharge.
The study intervention is placebo given once daily at a volume equivalent to 10 mg/kg of caffeine citrate. It is given orally, before hospital discharge and 28 days after discharge.
University of Alabama at Birmingham
Birmingham, Alabama, United States
Stanford University
Palo Alto, California, United States
Number of Days Between Randomization and Hospital Discharge
The number of days between randomization and hospital discharge. This outcome is censored at 48 weeks PMA and at time of transfer or death.
Time frame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
Number of Sick Visits Related to Apneic or Apparent Life-threatening Events Within First 4 Weeks Post-discharge
Number of sick visits related to apneic or apparent life-threatening events within first 4 weeks post-discharge MEASTYPE=SEC
Time frame: Discharge through 4 weeks post-discharge
The Number of Days to Physiologic Maturity After Randomization
The number of days to physiologic maturity after randomization. Physiologic maturity is defined: 1. Temperature: out of the incubator for at least 48 hours with normal body temperature; 2. Feeding: oral feeding at a volume of at least 140 ml/kg for 48 hours or growing on less than 140 ml/kg/day for at least 48 hours; 3. Respiratory: apnea-free for at least 5 consecutive days. This outcome is censored at 48 weeks PMA
Time frame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
The Number of Days to When Out of Incubator for 48 Hours: When Maintained Stable Temp for 48 Hrs
The number of days to when out of incubator for 48 hours: when maintained stable temp for 48 hrs. This outcome is censored at 48 weeks PMA
Time frame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
The Number of Days to Apnea/ Bradycardia Free for 5 Consecutive Days
The number of days to apnea/ bradycardia free for 5 consecutive days. This outcome is censored at 48 weeks PMA
Time frame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
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Emory University
Atlanta, Georgia, United States
University of Iowa
Iowa City, Iowa, United States
University of New Mexico
Albuquerque, New Mexico, United States
University of Rochester
Rochester, New York, United States
RTI International
Durham, North Carolina, United States
Duke University
Durham, North Carolina, United States
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States
...and 6 more locations
The Number of Days to Oral Feeds >140 ml/kg/Day or Growing on Less Than 140 ml/kg/Day for at Least 48 Hours
The number of days oral feeds \>140 ml/kg/day or growing on less than 140 ml/kg/day for at least 48 hours. This outcome is censored at 48 weeks PMA
Time frame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
Post-menstrual Age at Discharge
The post-menstrual age of the infant at discharge censored at 48 weeks PMA and at time of transfer or death
Time frame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
Weight Gain From Randomization Until Status
Weight gain from randomization until status %(discharge up to 48 wks PMA, with censoring at time of transfer or death%).
Time frame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
The Number of Days After Randomization Until Status That Infant Had at Least Two Consecutive Heart Rates >200 Documented at Least 3 Hours Apart
The number of days after randomization until status that infant had at least two consecutive heart rates \>200 documented at least 3 hours apart
Time frame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
Treatment for High Blood Pressure
Treatment for high blood pressure initiated after randomization until status.
Time frame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
The Number of Episodes Between Randomization and Status That Infant Was Placed NPO for >= 24 Hours
The number of episodes between randomization and status that infant was placed NPO for \>= 24 hours
Time frame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
Use of Anti-reflux Medications
The use of anti-reflux medications started between randomization and status
Time frame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
Number of Days That Significant Apnea/Bradycardia
The number of days that significant apnea/bradycardia, as defined by documentation of infant receiving any of the following between randomization and status: open label caffeine, other methylxanthines, doxapram, CPAP or ventilatory support for apnea/bradycardia.
Time frame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
All-cause Mortality
All-cause mortality
Time frame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
Number of All-cause Readmissions Within First 4 Weeks Post-discharge
Number of all-cause readmissions within first 4 weeks post-discharge
Time frame: Discharge through 4 weeks post-discharge
Number of All-cause Readmissions Within Second 4 Weeks Post-discharge
Number of all-cause readmissions within second 4 weeks post-discharge
Time frame: 4 weeks through 8 weeks post-discharge
Number of All-cause Readmissions Within First 8 Weeks Post-discharge
Number of all-cause readmissions within first 8 weeks post-discharge
Time frame: Discharge through 8 weeks post-discharge
Number of All-cause Sick Visits, Urgent Care, Emergency Rooms, or Health Care Provider%'s Office, Within First 4 Weeks Post-discharge
Number of all-cause sick visits, urgent care, emergency rooms, or health care provider%'s office, within first 4 weeks post-discharge
Time frame: Discharge through 4 weeks post-discharge
Number of All-cause Sick Visits, Urgent Care, Emergency Rooms, or Health Care Provider%'s Office, Within Second 4 Weeks Post-discharge
Number of all-cause sick visits, urgent care, emergency rooms, or health care provider%'s office, within second 4 weeks post-discharge
Time frame: 4 weeks through 8 weeks post-discharge
Number of All-cause Sick Visits, Urgent Care, Emergency Rooms, or Health Care Provider%'s Office, Within First 8 Weeks Post-discharge
Number of all-cause sick visits, urgent care, emergency rooms, or health care provider%'s office, within first 8 weeks post-discharge
Time frame: Discharge through 8 weeks post-discharge
Number of Sick Visits Related to Apneic or Apparent Life-threatening Events Within Second 4 Weeks Post-discharge
Number of sick visits related to apneic or apparent life-threatening events within second 4 weeks post-discharge
Time frame: 4 weeks through 8 weeks post-discharge
Number of Sick Visits Related to Apneic or Apparent Life-threatening Events Within First 8 Weeks Post-discharge
Number of sick visits related to apneic or apparent life-threatening events within first 8 weeks post-discharge
Time frame: Discharge through 8 weeks post-discharge