Moderately Preterm Infants With Caffeine at Home for Apnea (MoCHA) Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized Controlled Trial of Home Therapy With Caffeine Citrate in Moderately Preterm Infants With Apnea of Prematurity

Conditions
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Apnea of Prematurity

Intervention / Treatment
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* Drug: Caffeine Citrate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 29 Weeks
Maximum Age: 33 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Caffeine Citrate<br>Caffeine citrate at 10 mg/kg/dose (5 mg/kg caffeine base) daily, in hospital. Infants will continue at home on the same dose of caffeine citrate for the first 28 days after hospital discharge. | Drug: Caffeine Citrate<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Placebo contains all of the excipients except for the active ingredient, caffeine citrate, (a volume equivalent to 10 mg/kg of caffeine citrate) and given daily. Infants will be continued at home on the same dose of placebo for the first 28 days after hospital discharge. | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days of hospitalization | The number of days of hospitalization from randomization to discharge up to 48 weeks postmentrual age (PMA), with censoring at time of transfer or death. | Randomization until discharge up to 48 wks PMA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of days to physiologic maturity after randomization | Physiologic maturity is defined as: 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/day or growing on less than 140 ml/kg/day for at least 48 hours and 3) Respiratory: apnea-free for at least 5 days. The number of days to physiologic maturity after randomization up to 48 wks PMA, with censoring at time of transfer or death. | Randomization until physiologic maturity up to 48 wks PMA | 
| PMA at discharge | Post menstrual age at discharge up to 48 wks PMA, censoring at time of transfer or death. | Randomization until discharge up to 48 wks PMA | 
| The number of all-cause hospital re-admissions | The number of all-cause re-admissions to the hospital within the first four weeks, second four weeks, and first eight weeks combined among those discharged from the hospital by 48 wks PMA. | Discharge until eight weeks after discharge up to 52 wks PMA | 
| The number of all-cause sick visits | The number of all-cause sick visits to urgent care, emergency rooms, or health care provider's office within the first four weeks, second four weeks, and first eight weeks combined among those discharged from the hospital by 48 wks PMA. | Discharge until eight weeks after discharge up to 52 wks PMA | 
| Death | All cause mortalities | Randomization until eight weeks after discharge up to 52 wks PMA | 
| Weight | Weight will be recorded at time of of birth, randomization and at status: discharge up to 48 wks PMA ,with censoring at time of transfer or death | Randomization until discharge up to 48 wks PMA | 
| Elevated Heart Rate | The number of days after randomization that infant had at least two consecutive heart rates >200 documented at least 3 hours apart (when infant not crying) until discharge up to 48 wks PMA, with censoring at time of transfer or death | Randomization until discharge up to 48 wks PMA | 
| High Blood Pressure | Treatment for high blood pressure initiated after randomization until discharge up to 48 wks PMA, with censoring at time of transfer or death | Randomization until discharge up to 48 wks PMA | 
| Periods of NPO | The number of episodes between randomization and status (discharge up to 48 wks PMA, with censoring at time of transfer or death) that infant was placed NPO for ≥ 24 hours. | Randomization until discharge up to 48 wks PMA | 
| Reflux | The use of anti-reflux medications started between randomization and status (discharge up to 48 wks PMA, with censoring at time of transfer or death) | Randomization until discharge up to 48 wks PMA | 
| Significant Apnea | The number of days that significant apnea, as defined by receiving open label caffeine, CPAP for apnea or ventilatory support for apnea, is documented between randomization and status (discharge up to 48 wks PMA, with censoring at time of transfer or death) | Randomization until discharge up to 48 wks PMA | 
| Significant Bradycardia | The number of days that significant bradycardia, as defined by receiving treatment, is documented between randomization and status (discharge up to 48 wks PMA, with censoring at time of transfer or death) | Randomization until discharge up to 48 wks PMA | 
| Arrhythmia | The presence of documented and treated arrhythmias between randomization and status (discharge up to 48 wks PMA, with censoring at time of transfer or death), not due to tachycardia or bradycardia | Randomization until discharge up to 48 wks PMA | 
| Seizures | The onset of documented seizures, as defined by treating with anti-convulsants, between randomization and status (discharge up to 48 wks PMA, with censoring at time of transfer or death). | Randomization until discharge up to 48 wks PMA | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moderate preterm infant, Caffeine citrate