Clinical trial NCT03340727: Moderately Preterm Infants With Caffeine at Home for Apnea (MoCHA) Trial
Official title: Randomized Controlled Trial of Home Therapy With Caffeine Citrate in Moderately Preterm Infants With Apnea of Prematurity
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Apnea of Prematurity
Keywords: Moderate preterm infant
Caffeine citrate
Lead sponsor: NICHD Neonatal Research Network
Sponsor class: NETWORK
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2017-11-13
Enrollment: 827
Sex: ALL
Minimum age (years): 29
Maximum age (years): 33
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Sample size for this trial will be flexible: the trial will be stopped for efficacy or futility based on pre-determined statistical thresholds or based on study drug availability.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Inborn and outborn infants of 29 0/7 to 33 6/7 weeks gestational age at birth
* admitted to hospitals of the NICHD NRN who, are at time of enrollment:
* ≤35 6/7 weeks post-menstrual age at the time of randomization
* Receiving caffeine with plan to discontinue treatment or just discontinued caffeine treatment
* Receiving feeds at a volume of ≥120 ml/kg/day by oral and/or tube feeding
* Ability to start study medication within 72 hours after stopping caffeine

Exclusion Criteria:

* On respiratory therapy (oxygen more than room air equivalent for high altitude sites, nasal cannula, continuous positive pressure ventilation, and/or mechanical ventilation)
* Infants who would otherwise be discharged home on apnea monitor due to underlying disease or family history, including history of a sibling with sudden infant death syndrome
* Parental request for apnea monitor
* Congenital heart disease other than atrial septal defect, ventricular septal defect, or patent ductus arteriosus
* Neuromuscular conditions affecting respiration
* Major congenital malformation and/or genetic disorder
* Plans to transfer to a non-NRN site before discharge
* Unable to obtain parental or guardian consent

Primary outcomes:
measure: Number of Days Between Randomization and Hospital Discharge
timeFrame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
measure: Number of Sick Visits Related to Apneic or Apparent Life-threatening Events Within First 4 Weeks Post-discharge
timeFrame: Discharge through 4 weeks post-discharge
Secondary outcomes:
measure: The Number of Days to Physiologic Maturity After Randomization
timeFrame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
measure: The Number of Days to When Out of Incubator for 48 Hours: When Maintained Stable Temp for 48 Hrs
timeFrame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
measure: The Number of Days to Apnea/ Bradycardia Free for 5 Consecutive Days
timeFrame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
measure: 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
timeFrame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
measure: Post-menstrual Age at Discharge
timeFrame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
measure: Weight Gain From Randomization Until Status
timeFrame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
measure: The Number of Days After Randomization Until Status That Infant Had at Least Two Consecutive Heart Rates >200 Documented at Least 3 Hours Apart
timeFrame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
measure: Treatment for High Blood Pressure
timeFrame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
measure: The Number of Episodes Between Randomization and Status That Infant Was Placed NPO for >= 24 Hours
timeFrame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
measure: Use of Anti-reflux Medications
timeFrame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
measure: Number of Days That Significant Apnea/Bradycardia
timeFrame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
measure: All-cause Mortality
timeFrame: Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
measure: Number of All-cause Readmissions Within First 4 Weeks Post-discharge
timeFrame: Discharge through 4 weeks post-discharge
measure: Number of All-cause Readmissions Within Second 4 Weeks Post-discharge
timeFrame: 4 weeks through 8 weeks post-discharge
measure: Number of All-cause Readmissions Within First 8 Weeks Post-discharge
timeFrame: Discharge through 8 weeks post-discharge
measure: Number of All-cause Sick Visits, Urgent Care, Emergency Rooms, or Health Care Provider%'s Office, Within First 4 Weeks Post-discharge
timeFrame: Discharge through 4 weeks post-discharge
measure: Number of All-cause Sick Visits, Urgent Care, Emergency Rooms, or Health Care Provider%'s Office, Within Second 4 Weeks Post-discharge
timeFrame: 4 weeks through 8 weeks post-discharge
measure: Number of All-cause Sick Visits, Urgent Care, Emergency Rooms, or Health Care Provider%'s Office, Within First 8 Weeks Post-discharge
timeFrame: Discharge through 8 weeks post-discharge
measure: Number of Sick Visits Related to Apneic or Apparent Life-threatening Events Within Second 4 Weeks Post-discharge
timeFrame: 4 weeks through 8 weeks post-discharge
measure: Number of Sick Visits Related to Apneic or Apparent Life-threatening Events Within First 8 Weeks Post-discharge
timeFrame: Discharge through 8 weeks post-discharge
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: RTI International
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University, Rainbow Babies and Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Research Institute at Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Brown University, Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Alabama at Birmingham
name: Waldemar Carlo, MD
role: PRINCIPAL_INVESTIGATOR
References: