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

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

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 Overview

• Status: Terminated
• Conditions: Apnea of Prematurity
• Intervention / Treatment: Drug: Caffeine Citrate; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 827
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Durham, North Carolina, United States, 27705
      • RTI International
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Cincinnati Children's Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University, Rainbow Babies and Children's Hospital
    • Columbus, Ohio, United States, 43205
      • Research Institute at Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Brown University, Women & Infants Hospital of Rhode Island
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center at Dallas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 7 months (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Caffeine Citrate; 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; 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.
Placebo Comparator: Placebo; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	Discharge through 4 weeks post-discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	Randomization through hospital discharge, censored at time of transfer, death, or 48 wks 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	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	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	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%).	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	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.	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	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	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.	Randomization through hospital discharge, censored at time of transfer, death, or 48 wks PMA
All-cause Mortality	All-cause mortality	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	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	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	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	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	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	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	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	Discharge through 8 weeks post-discharge

Collaborators and Investigators

• Sponsor: NICHD Neonatal Research Network
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Waldemar Carlo, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2019
• Primary Completion (Actual): January 23, 2023
• Study Completion (Actual): March 20, 2023

Study Registration Dates

• First Submitted: November 3, 2017
• First Submitted That Met QC Criteria: November 8, 2017
• First Posted (Actual): November 13, 2017

Study Record Updates

• Last Update Posted (Actual): July 31, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Moderate preterm infant; Caffeine citrate
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Apnea; Premature Birth; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine; Caffeine citrate
• Other Study ID Numbers: NICHD-NRN-0056; UG1HD034216 (U.S. NIH Grant/Contract); UG1HD027904 (U.S. NIH Grant/Contract); UG1HD021364 (U.S. NIH Grant/Contract); UG1HD027853 (U.S. NIH Grant/Contract); UG1HD040689 (U.S. NIH Grant/Contract); UG1HD040492 (U.S. NIH Grant/Contract); UG1HD027851 (U.S. NIH Grant/Contract); UG1HD087229 (U.S. NIH Grant/Contract); UG1HD053109 (U.S. NIH Grant/Contract); UG1HD068278 (U.S. NIH Grant/Contract); UG1HD068244 (U.S. NIH Grant/Contract); UG1HD068263 (U.S. NIH Grant/Contract); UG1HD027880 (U.S. NIH Grant/Contract); UG1HD053089 (U.S. NIH Grant/Contract); UG1HD087226 (U.S. NIH Grant/Contract); U10HD036790 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Per NIH Data Sharing Plan

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No