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RecruitingNCT06026163CAT/LPTUpdated Jun 27, 2025

Caffeine as an Adjuvant Therapy for Late Preterm Infants With Respiratory Distress

A Phase 2/3 interventional study of Caffeine citrate and Placebo in Prematurity, Respiratory Disease and Ventilator Lung; Newborn, sponsored by Ministry of Health, Saudi Arabia. Recruiting at 2 sites in Saudi Arabia. Open to participants aged 1 Day to 3 Days. Per ClinicalTrials.gov, last updated 2025-06-27.

Sponsored by Ministry of Health, Saudi Arabia · Phase 2/3, Interventional, and Treatment

From the registry’s dates

  • Started Oct 2023; still recruiting 3 years later.
Phase
Phase 2/3
Study type
Interventional
Enrollment
134
Allocation
Randomized
Ages
1 Day to 3 Days
Sex
All
01

Study summary

Use of caffeine citrate in late-preterm infants with respiratory distress is questionable. Oliphant and colleagues found in a recently published study that caffeine therapy use in late-preterm infants at a loading dose of 20 and 40 mg/kg and maintenance dose of 10 and 20 mg/kg/day reduces the incidence of intermittent hypoxia events by 61 and 67% respectively.

The investigators hypothesized that caffeine will improve respiratory drive, prevent apnea, shorten the hospital stay and improve arousal state in late preterm infants.

The investigators aim to study the effect of caffeine citrate on late preterm babies as regard duration of respiratory support, duration of hospital stay, respiratory morbidity, incidence and frequency of apnea.

Read the detailed description

late preterm infants will be randomized in a blinded manner to receive either caffeine in loading dose 20 mg/kg (equivalent for 10 mg/kg caffeine base) and maintenance dose 10 mg/kg/day (equivalent for 5 mg/kg caffeine base) in Caffeine treatment group, or equivalent volume of saline in the placebo group. Caffeine will be continued until infants get off all forms of respiratory support.

Preparation of caffeine and placebo will be performed by a designated pharmacist who is not part of the study. Parents and investigators will be remained blinded to the administered medications throughout the study period.

02

Conditions studied

  • Prematurity
  • Respiratory Disease
  • Ventilator Lung; Newborn

Keywords

  • caffeine
  • preterm
  • newborn
  • respiratory support
03

In context

Premature Birth

2,550 studies on the registry are indexed under Premature Birth; 500 are open to participants now.

This study's planned enrollment of 134 is above the median of 84 across 1,666 interventional studies indexed under Premature Birth.

Browse Premature Birth studies →

Lead sponsor

Ministry of Health, Saudi Arabia is the lead sponsor of 21 studies on the registry; 8 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
1 Day to 3 Days
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Newborn infants at gestational age 34 0/7 through 36 6/7
  • Presented with respiratory distress
  • Require respiratory support in the form of any of the following :

A) Invasive mechanical ventilation, B) Non-invasive positive pressure ventilation, C) Nasal cannula with FIO2 requirement over 50% to keep pre-ductal saturation between 90-95%.

Exclusion criteria

Exclusion Criteria:

1 - Late preterm admitted for non-respiratory etiologies 2- Late preterm infants requiring nasal cannula on less than 50% FIO2 by 4 hours of age as they are less likely to require respiratory support for a long time.

3- Newborn infants with congenital malformations and chromosomal anomalies. 4- Infants with echocardiographic evidence of PPHN requiring medical intervention.

5- Late preterm with history of maternal substance abuse

05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
134 participants (estimated)

Study arms

  • Experimental
    Caffeine citrate group

    Infants receive either caffeine citrate in loading dose 20 mg/kg (equivalent for 10 mg/kg caffeine base) and maintenance dose 10 mg/kg/day (equivalent for 5 mg/kg caffeine base).

    Drug: Caffeine citrate

  • Placebo comparator
    Control group

    Infants received equivalent volume of saline.

    Other: Placebo

Interventions

  • Caffeine citrate in loading dose 20 mg/kg (equivalent for 10 mg/kg caffeine base) and maintenance dose 10 mg/kg/day (equivalent for 5 mg/kg caffeine base)

    Also known as: Intervention group

  • OtherPlacebo

    Equivalent volume of saline

    Also known as: Saline

06

What researchers measure

Primary outcomes

  1. Duration of respiratory support

    cumulative duration of mechanical ventilation, non-invasive positive pressure ventilation and nasal cannula therapy (days)

    Time frame: 28 days

Secondary outcomes

  1. Episodes of apnea

    the cessation of breathing for more than 20 seconds or cessation of breathing for accompanied by bradycardia or desaturation

    Time frame: 28 gays

  2. Failure of extubation

    need of re-intubation within 72 h of extubation from mechanical ventilation

    Time frame: 28 days

  3. Duration of caffeine

    Days of caffeine treatment

    Time frame: 28 days

  4. Length of hospital stay

    days of hospital admission

    Time frame: 28 days

  5. Time to full enteral and oral feeding

    days to reach full enteral feeds

    Time frame: 28 days

  6. Adverse effects of caffeine use

    Tachycardia, irritability, feeding intolerance, hypertension

    Time frame: 28 days

  7. Caffeine withhold

    Caffeine withhold for suspected side effects

    Time frame: 28 days

  8. Weight gain per day

    Weight gain per day (gram)

    Time frame: 28 days

  9. Mortality

    Death before hospital discharge

    Time frame: 28 days

  10. Readmission rate

    Readmission to the hospital with respiratory related symptoms within 48 hours of hospital discharge

    Time frame: 28 days

  11. Days of apnea

    Days of apnea

    Time frame: 28 days

07

Study locations

2 of 2 sites recruiting
08

References and documents

Publications

  • Davis PG, Schmidt B, Roberts RS, Doyle LW, Asztalos E, Haslam R, Sinha S, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. J Pediatr. 2010 Mar;156(3):382-7. doi: 10.1016/j.jpeds.2009.09.069. Epub 2009 Nov 18. PubMed 19926098 ↗
  • Eichenwald EC; Committee on Fetus and Newborn, American Academy of Pediatrics. Apnea of Prematurity. Pediatrics. 2016 Jan;137(1). doi: 10.1542/peds.2015-3757. Epub 2015 Dec 1. PubMed 26628729 ↗

Individual participant data

Plan to share: Yes — Data obtained through this study may be provided to qualified researchers for research and scientific purposes (i.e conduction of meta-analysis or systematic review). Data or samples shared will be coded, with no protected health information included. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party.

Supporting information: Study protocol

Time frame: Data requests can be submitted starting 3 months after article publication and the data will be made accessible for up to 12 months. Extensions will be considered on a case-by-case basis."

Access criteria: Access to raw data (no protected health information) can be requested by qualified researchers for scientific purposes, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA)

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Oct 2023 (actual). Primary completion is estimated for Oct 2027, 48 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Aug 27, 2023
First posted
Sep 6, 2023
StartActual
Oct 12, 2023
Primary completionEst.
Oct 30, 2027
CompletionEst.
Jan 1, 2028
Last update
Jun 27, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jun 27, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06026163
Lead sponsor
Ministry of Health, Saudi Arabia
Responsible party
Fatema Sulaiman Alhazmi (NICU Director, Ministry of Health, Saudi Arabia) — Principal investigator
First posted
Sep 6, 2023
Start date
Oct 12, 2023
Primary completion
Oct 30, 2027 (estimated)
Completion
Jan 1, 2028 (estimated)
Last update
Jun 27, 2025

Study contacts

Ohoud Almoualled, Dr
Contact
o.doc2or@gmail.com
+966500550679
Nehad Nasef
principal investigator · Neonatology Consultant

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Caffeine citrate

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