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

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

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03340727

Acronym

MoCHA

Enrollment

827

Registered

2017-11-13

Start date

2019-02-27

Completion date

2023-03-20

Last updated

2024-07-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Apnea of Prematurity

Keywords

Moderate preterm infant, Caffeine citrate

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.

Interventions

DRUGCaffeine Citrate

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.

DRUGPlacebo

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

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.

Eligibility

Sex/Gender

ALL

Age

29 Weeks to 33 Weeks

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Days Between Randomization and Hospital Discharge	Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA	The number of days between randomization and hospital discharge. This outcome is censored at 48 weeks PMA and at time of transfer or death.
Number of Sick Visits Related to Apneic or Apparent Life-threatening Events Within First 4 Weeks Post-discharge	Discharge through 4 weeks post-discharge	Number of sick visits related to apneic or apparent life-threatening events within first 4 weeks post-discharge MEASTYPE=SEC

Secondary

Measure	Time frame	Description
The Number of Days to Apnea/ Bradycardia Free for 5 Consecutive Days	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. This outcome is censored at 48 weeks PMA
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	Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA	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
Post-menstrual Age at Discharge	Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA	The post-menstrual age of the infant at discharge censored at 48 weeks PMA and at time of transfer or death
Weight Gain From Randomization Until Status	Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA	Weight gain from randomization until status %(discharge up to 48 wks PMA, with censoring at time of transfer or death%).
The Number of Days After Randomization Until Status That Infant Had at Least Two Consecutive Heart Rates >200 Documented at Least 3 Hours Apart	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
Treatment for High Blood Pressure	Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA	Treatment for high blood pressure initiated after randomization until status.
The Number of Episodes Between Randomization and Status That Infant Was Placed NPO for >= 24 Hours	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
Use of Anti-reflux Medications	Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA	The use of anti-reflux medications started between randomization and status
Number of Days That Significant Apnea/Bradycardia	Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA	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.
The Number of Days to Physiologic Maturity After Randomization	Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA	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
Number of All-cause Readmissions Within First 4 Weeks Post-discharge	Discharge through 4 weeks post-discharge	Number of all-cause readmissions within first 4 weeks post-discharge
Number of All-cause Readmissions Within Second 4 Weeks Post-discharge	4 weeks through 8 weeks post-discharge	Number of all-cause readmissions within second 4 weeks post-discharge
Number of All-cause Readmissions Within First 8 Weeks Post-discharge	Discharge through 8 weeks post-discharge	Number of all-cause readmissions within first 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	Discharge through 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
Number of All-cause Sick Visits, Urgent Care, Emergency Rooms, or Health Care Provider%'s Office, Within Second 4 Weeks Post-discharge	4 weeks through 8 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 First 8 Weeks Post-discharge	Discharge 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 Sick Visits Related to Apneic or Apparent Life-threatening Events Within Second 4 Weeks Post-discharge	4 weeks 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 First 8 Weeks Post-discharge	Discharge through 8 weeks post-discharge	Number of sick visits related to apneic or apparent life-threatening events within first 8 weeks post-discharge
All-cause Mortality	Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA	All-cause mortality
The Number of Days to When Out of Incubator for 48 Hours: When Maintained Stable Temp for 48 Hrs	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. This outcome is censored at 48 weeks PMA

Countries

United States

Participant flow

Recruitment details

Infants were recruited into the study based on eligibility and parental/guardian consent. Baseline characteristics of the mother were collected (with consent) for use in statistical analysis.

Participants by arm

Arm	Count
Caffeine Daily weight-adjusted doses of Caffeine Citrate while in the hospital, followed by 4 weeks of at home administration by parent/guardians	416
Placebo Daily weight-adjusted doses of Placebo while in the hospital, followed by 4 weeks of at home administration by parent/guardians	411
Total	827

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	1	0
Overall Study	Lost to Follow-up	31	35
Overall Study	Still in hospital at 48 0/7 wks Post-menstrual Age (PMA)	1	1
Overall Study	Transferred to another facility	10	7
Overall Study	Withdrawal by Subject	28	17

Baseline characteristics

Characteristic	Placebo	Total	Caffeine
Age, Continuous	29.9 years STANDARD_DEVIATION 5.8	29.9 years STANDARD_DEVIATION 5.8	30 years STANDARD_DEVIATION 5.8
Apgar score of Infant at 1 minute after birth	6 score	6 score	6 score
Apgar score of Infant at 5 minutes after birth	8 score	8 score	8 score
Birth weight of infant	1564.3 grams STANDARD_DEVIATION 357.4	1554.6 grams STANDARD_DEVIATION 357.7	1545 grams STANDARD_DEVIATION 358.1
Gestational Age	31.2 weeks STANDARD_DEVIATION 1.2	31.2 weeks STANDARD_DEVIATION 1.2	31.2 weeks STANDARD_DEVIATION 1.2
Gravidity	2 years	2 years	2.5 years
Marital status Married	233 Participants	446 Participants	213 Participants
Marital status Single	175 Participants	375 Participants	200 Participants
Marital status Unknown	3 Participants	6 Participants	3 Participants
Mothers education, Customized 8th grade or less	5 Participants	14 Participants	9 Participants
Mothers education, Customized 9th to 12th grade	22 Participants	55 Participants	33 Participants
Mothers education, Customized College degree	75 Participants	143 Participants	68 Participants
Mothers education, Customized Graduate degree	38 Participants	76 Participants	38 Participants
Mothers education, Customized High School degree	102 Participants	188 Participants	86 Participants
Mothers education, Customized Partial college/Associate degree	90 Participants	183 Participants	93 Participants
Mothers education, Customized Trade or technical school	10 Participants	20 Participants	10 Participants
Mothers education, Customized Unknown	69 Participants	148 Participants	79 Participants
Mothers insurance, Customized Private	213 Participants	420 Participants	207 Participants
Mothers insurance, Customized Public	190 Participants	393 Participants	203 Participants
Mothers insurance, Customized Self-pay/uninsured	7 Participants	13 Participants	6 Participants
Mothers insurance, Customized Unknown	1 Participants	1 Participants	0 Participants
Number of Infants who Required Chest compressions No	405 Participants	821 Participants	416 Participants
Number of Infants who Required Chest compressions Unknown	1 Participants	1 Participants	0 Participants
Number of Infants who Required Chest compressions Yes	5 Participants	5 Participants	0 Participants
Number of Infants who Required CPAP No	81 Participants	162 Participants	81 Participants
Number of Infants who Required CPAP Unknown	1 Participants	1 Participants	0 Participants
Number of Infants who Required CPAP Yes	329 Participants	664 Participants	335 Participants
Number of Infants who Required Epinephrine No	409 Participants	825 Participants	416 Participants
Number of Infants who Required Epinephrine Yes	2 Participants	2 Participants	0 Participants
Number of Infants who Required Intubation No	366 Participants	736 Participants	370 Participants
Number of Infants who Required Intubation Yes	45 Participants	91 Participants	46 Participants
Number of Infants who Required Oxygen No	68 Participants	139 Participants	71 Participants
Number of Infants who Required Oxygen Unknown	1 Participants	2 Participants	1 Participants
Number of Infants who Required Oxygen Yes	342 Participants	686 Participants	344 Participants
Number of Infants who Required Positive pressure ventilation No	185 Participants	373 Participants	188 Participants
Number of Infants who Required Positive pressure ventilation Unknown	1 Participants	1 Participants	0 Participants
Number of Infants who Required Positive pressure ventilation Yes	225 Participants	453 Participants	228 Participants
Parity	2 years	2 years	2 years
Race/Ethnicity, Customized American Indian or Alaskan Native	12 Participants	19 Participants	7 Participants
Race/Ethnicity, Customized Asian	9 Participants	21 Participants	12 Participants
Race/Ethnicity, Customized Black	110 Participants	220 Participants	110 Participants
Race/Ethnicity, Customized Hispanic or Latino	54 Participants	117 Participants	63 Participants
Race/Ethnicity, Customized More Than One Race	2 Participants	5 Participants	3 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	4 Participants	8 Participants	4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	345 Participants	683 Participants	338 Participants
Race/Ethnicity, Customized Unknown	2 Participants	4 Participants	2 Participants
Race/Ethnicity, Customized Unknown or Not Reported	10 Participants	24 Participants	13 Participants
Race/Ethnicity, Customized White	261 Participants	526 Participants	265 Participants
Sex/Gender, Customized Female	207 Participants	420 Participants	213 Participants
Sex/Gender, Customized Male	204 Participants	407 Participants	203 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	1 / 416	0 / 411
other Total, other adverse events	10 / 416	24 / 411
serious Total, serious adverse events	12 / 416	22 / 411

Outcome results

Primary

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