Premature Infant DiseasePhase 4NCT06518603
Caffeine Citrate in Preterm Infants at Risk of Apnea in Zambia
A Phase 4 study testing Caffeine citrate 20mg/kg/day in people with Premature Infant Disease and Apnea of Prematurity, run by University of Alabama at Birmingham at 1 site in Zambia.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 days to 12 months
- Conditions the study is for
- Premature Infant Disease, Apnea of Prematurity, Development, Infant
- What is being tested?
- Caffeine citrate 20mg/kg/day
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 340 participants
- Where
- 1 siteZambia
- Study dates
- 17 Jun 2026to 30 Jun 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 days to 12 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Newborns:
- 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,
- On methylxanthines with plans to discontinue on methylxanthine,
- Off oxygen therapy for >48 hours at the time of evaluation for eligibility,
- Receiving full daily feeds,
- Deemed stable and ready to go off caffeine as recommended by the Neonatologist
- 18+ years of age (parent)
Who cannot join
- Newborns with neuromuscular conditions affecting respiration,
- Major congenital malformations and genetic disorders,
- Unable to obtain parental or guardian consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Zambia1 site, 1 recruiting
- Recruiting
University Teaching Hospital
Lusaka, Lusaka Province, 10100
Albert Manasyan, MD, +260 976 448 994, Albert.Manasyan@cidrz.org
Waldemar A Carlo, MD, 2059344680, wacarlo@uabmc.edu
About this study
Official title: Randomized Controlled Trial of Caffeine Citrate in Preterm Infants at Risk of Apnea in Zambia
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:
Read more
- Does continued treatment of moderately preterm newborns with caffeine citrate after hospital discharge prevent or decrease apneic events that result in sick visits?
- 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:
- 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
- Keep a diary of symptoms and any apneic events
- Check in with researchers via telephone call once a week
- Return to clinic for infant physical examination at 28 days
- Return to the clinic for infant physical examination at 2 months
- Return to clinic for infant neurodevelopmental examination with Ages and Stages Questionnaire at 12 months of age
Read the 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.
- Being tested
- Caffeine citrate 20mg/kg/day, Placebo-Sterile water 1ml/kg/day
- Medical subject headings
- Apnea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Caffeine citrate 20mg/kg/dayDrug
Caffeine citrate 20mg/kg/day given orally once daily for 28 days
Placebo-Sterile water 1ml/kg/dayDrug
Placebo-sterile water 1mg/kg/day given orally once daily for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Oral Caffeine Citrate 20mg/kg/day | Experimental | Caffeine Citrate 20 mg/kg/day given orally once a day for 28 days. (2mg/ml) Receives: Drug: Caffeine citrate 20mg/kg/day |
| Placebo | Placebo comparator | Sterile water 1ml/kg/day given orally once a day for 28 days. Receives: Drug: Placebo-Sterile water 1ml/kg/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of apneic events
Documentation or report of apnea of prematurity [AoP], a condition exhibited by cessation of breathing for ≥20 or <20 seconds accompanied by bradycardia and/or cyanosis
Measured: 28 days after discharge
Number of visits to healthcare professionals related to apneic events
Documentation or report of sick visit
Measured: 28 days after discharge
Secondary outcomes (3)
Number of all-cause sick visits
Documentation or report of sick visit
Measured: 2 months after discharge
Percentage of neonatal mortality within 2 months after discharge
Documentation of neonatal death
Measured: 2 months after discharge
Infant/Child Developmental Assessment
Score on "Ages and Stages Questionnaire" obtained at clinic visit
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2024
- Study start17 Jun 2026
- Primary completion31 May 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Premature Infant DiseaseStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double blind, placebo-controlled, 1:1 parallel allocation
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 340 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- University Teaching Hospital, Lusaka, Zambia, Centre for Infectious Disease Research in Zambia
- Responsible party
- Principal investigator, Albert Manasyan, MD, MPH, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06518603
- Sponsor's protocol ID
- UAB-300013205
- Other IDs
- UAB Dixon End Chair/3102800, 000533428-0004
- Status last verified
- Jun 2026
- First submitted
- 18 Jul 2024
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial of Caffeine Citrate in Preterm Infants at Risk of Apnea in Zambia
- ClinicalTrials.gov ID
- NCT06518603
- Acronym / sponsor ID
- UAB-300013205
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 340 participants (estimated)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- University Teaching Hospital, Lusaka, Zambia, Centre for Infectious Disease Research in Zambia
- Study start
- 17 Jun 2026 (actual)
- Primary completion
- 31 May 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 24 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Does continued treatment of moderately preterm newborns with caffeine citrate after hospital discharge prevent or decrease apneic events that result in sick visits?
- 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:
- 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
- Keep a diary of symptoms and any apneic events
- Check in with researchers via telephone call once a week
- Return to clinic for infant physical examination at 28 days
- Return to the clinic for infant physical examination at 2 months
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double blind, placebo-controlled, 1:1 parallel allocation
| Arm | Type | Receives |
|---|---|---|
| Oral Caffeine Citrate 20mg/kg/day | Experimental | Drug: Caffeine citrate 20mg/kg/dayCaffeine Citrate 20 mg/kg/day given orally once a day for 28 days. (2mg/ml) |
| Placebo | Placebo comparator | Drug: Placebo-Sterile water 1ml/kg/daySterile water 1ml/kg/day given orally once a day for 28 days. |
Who may qualify
- Ages
- 0 days to 12 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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,
- On methylxanthines with plans to discontinue on methylxanthine,
- Off oxygen therapy for >48 hours at the time of evaluation for eligibility,
- Receiving full daily feeds,
- Deemed stable and ready to go off caffeine as recommended by the Neonatologist
Key exclusion criteria (3 listed)
- Newborns with neuromuscular conditions affecting respiration,
- Major congenital malformations and genetic disorders,
- Unable to obtain parental or guardian consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Caffeine citrate 20mg/kg/dayCaffeine citrate 20mg/kg/day given orally once daily for 28 days | Drug | Oral Caffeine Citrate 20mg/kg/day |
| Placebo-Sterile water 1ml/kg/dayPlacebo-sterile water 1mg/kg/day given orally once daily for 28 days | Drug | Placebo |
Primary outcome
Number of apneic events
Time frame: 28 days after discharge
Documentation or report of apnea of prematurity [AoP], a condition exhibited by cessation of breathing for ≥20 or <20 seconds accompanied by bradycardia and/or cyanosis
Number of visits to healthcare professionals related to apneic events
Time frame: 28 days after discharge
Documentation or report of sick visit
3 secondary outcomes
Number of all-cause sick visits
Time frame: 2 months after discharge
Percentage of neonatal mortality within 2 months after discharge
Time frame: 2 months after discharge
Infant/Child Developmental Assessment
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Caffeine citrate 20mg/kg/day in people with Premature Infant Disease and Apnea of Prematurity, run by University of Alabama at Birmingham at 1 site in Zambia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Zambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Albert Manasyan, MD (+260 976 448 994, Albert.Manasyan@cidrz.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of apneic events (time frame: 28 days after discharge). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.