Clinical trial NCT06518603: Caffeine Citrate in Preterm Infants at Risk of Apnea in Zambia
Official title: Randomized Controlled Trial of Caffeine Citrate in Preterm Infants at Risk of Apnea in Zambia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Premature Infant Disease
Apnea of Prematurity
Development, Infant
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: University Teaching Hospital, Lusaka, Zambia
name: Centre for Infectious Disease Research in Zambia
First posted: 2024-07-24
Enrollment: 340
Sex: ALL
Minimum age (years): 0
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind, placebo-controlled, 1:1 parallel allocation
Primary purpose: PREVENTION

Brief summary: The goal of this clinical trial is to learn if caffeine citrate prevents apneic events that result in sick visits in moderately preterm infants after discharge from the hospital. It will also learn if the use of caffeine leads to better developmental outcomes at 12 months of age.

Our research questions are:

1. Does continued treatment of moderately preterm newborns with caffeine citrate after hospital discharge prevent or decrease apneic events that result in sick visits?
2. Will the continued use of caffeine citrate lead to improved developmental outcomes among infants at 12 months of age?

Researchers will compare caffeine citrate to a placebo (a look-alike substance that contains no drug) to see if caffeine citrate prevents apneic spells which result in healthcare visits.

Parents of participants will:

1. Administer caffeine citrate 20mg/kg/day or a placebo (equivalent volume of sterile water) orally every day for up to 28 days after hospital discharge
2. Keep a diary of symptoms and any apneic events
3. Check in with researchers via telephone call once a week
4. Return to clinic for infant physical examination at 28 days
5. Return to the clinic for infant physical examination at 2 months

5. Return to clinic for infant neurodevelopmental examination with Ages and Stages Questionnaire at 12 months of age

Detailed description: Once an infant has been deemed stable by the neonatologist and the neonatologist recommends discontinuing treatment for apnea of prematurity 5 days before hospital discharge as per standard of care, the parent/guardian will be approached for consent. Following consent, study participants will be randomized to either the Intervention Arm (20mg/kg/day caffeine citrate; 2mg/ml) dose and equal volume of placebo (sterile water) using trial-specific single dose caffeine/placebo vials. Upon the study participant's hospital discharge, the pharmacist will prepare the caffeine citrate and placebo relevant to the weight of the infant within 48 hours prior to discharge. The doses will not be adjusted for weight gain after discharge. Caffeine levels will not be checked routinely and checking levels will be discouraged to optimize masking.

While at the hospital, infants will receive the oral dose from government staff. Following hospital discharge, the parent/guardian will be given enough doses of caffeine or equivalent placebo for 28 days and will be asked to administer it to their infant orally daily, at the same time, until day 28. Unlike the intervention arm, all study participants randomized to the control arm (placebo) will discontinue receiving caffeine and will begin receiving placebo (sterile water) in the same volume orally as those in the intervention arm. The parent/guardian will also be given a booklet to register any apneic spells. The study RA will contact the parent/guardian on a weekly basis, up to day 28 and once at 2 months after hospital discharge for patient clinical monitoring and follow-up purposes.

Upon completion of the study at 12 months of life, all study participants will return to the hospital for neurodevelopmental screening using the Ages and Stages-3 Questionnaire for 12 months.

Data will be collected onto paper forms, which will then be entered into a REDCap Database, housed at the Centre for Infectious Disease Research in Zambia (CIDRZ) offices. Data forms will be kept in locked cabinets, retained and destroyed per incineration after 5 years. Access to the data forms and REDCap Database will be restricted to those with a need to know.

Eligibility criteria: Inclusion Criteria:

Newborns:

1. 29 0/7 to 33 6/7 weeks GA (or with a birth weight 1.0 to 2.0 kg if pregnancy dating is unreliable) admitted to the UTH NICU,
2. On methylxanthines with plans to discontinue on methylxanthine,
3. Off oxygen therapy for \>48 hours at the time of evaluation for eligibility,
4. Receiving full daily feeds,
5. Deemed stable and ready to go off caffeine as recommended by the Neonatologist
6. 18+ years of age (parent)

Exclusion Criteria:

1. Newborns with neuromuscular conditions affecting respiration,
2. Major congenital malformations and genetic disorders,
3. Unable to obtain parental or guardian consent

Primary outcomes:
measure: Number of apneic events
timeFrame: 28 days after discharge
measure: Number of visits to healthcare professionals related to apneic events
timeFrame: 28 days after discharge
Secondary outcomes:
measure: Number of all-cause sick visits
timeFrame: 2 months after discharge
measure: Percentage of neonatal mortality within 2 months after discharge
timeFrame: 2 months after discharge
measure: Infant/Child Developmental Assessment
timeFrame: 12 months
Other outcomes:
Locations:
city: Lusaka
country: Zambia
facility: University Teaching Hospital
state: Lusaka Province
Study officials:
References: