Caffeine as an Adjuvant Therapy for Late Preterm Infants With Respiratory Distress (CAT/LPT)

Caffeine for Late Preterm Infants: A Double Blind Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Disease; Prematurity; Ventilator Lung; Newborn
• Intervention / Treatment: Drug: Caffeine citrate; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 134
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Ohoud Almoualled, Dr; Phone Number: +966500550679; Email: o.doc2or@gmail.com

Study Locations

• Saudi Arabia
  • Medina, Saudi Arabia, 42319
    • Recruiting
    • King Salman Bin Abdulaziz Medical City
    • Contact: Yasmeen T Aljhani; Phone Number: +966148499629; Email: med-ksamc-irb@moh.gov.sa
    • Principal Investigator: Nehad Nasef
  • Medina, Saudi Arabia
    • Recruiting
    • King Salman Bin Abdulaziz Medical City
    • Contact: Yasmeen T Aljhani; Phone Number: +966148499629; Email: med-ksamc-irb@moh.gov.sa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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:

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

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 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; 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); Other Names: Intervention group
Placebo Comparator: Control group; Infants received equivalent volume of saline.	Other: Placebo; Equivalent volume of saline; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of respiratory support	cumulative duration of mechanical ventilation, non-invasive positive pressure ventilation and nasal cannula therapy (days)	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Episodes of apnea	the cessation of breathing for more than 20 seconds or cessation of breathing for accompanied by bradycardia or desaturation	28 gays
Failure of extubation	need of re-intubation within 72 h of extubation from mechanical ventilation	28 days
Duration of caffeine	Days of caffeine treatment	28 days
Length of hospital stay	days of hospital admission	28 days
Time to full enteral and oral feeding	days to reach full enteral feeds	28 days
Adverse effects of caffeine use	Tachycardia, irritability, feeding intolerance, hypertension	28 days
Caffeine withhold	Caffeine withhold for suspected side effects	28 days
Weight gain per day	Weight gain per day (gram)	28 days
Mortality	Death before hospital discharge	28 days
Readmission rate	Readmission to the hospital with respiratory related symptoms within 48 hours of hospital discharge	28 days
Days of apnea	Days of apnea	28 days

Collaborators and Investigators

• Sponsor: Ministry of Health, Saudi Arabia
• Investigators: Principal Investigator: Nehad Nasef, Neonatology Consultant

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2023
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: August 27, 2023
• First Submitted That Met QC Criteria: September 3, 2023
• First Posted (Actual): September 6, 2023

Study Record Updates

• Last Update Posted (Actual): June 27, 2025
• Last Update Submitted That Met QC Criteria: June 24, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: preterm; caffeine; newborn; respiratory support
• Additional Relevant MeSH Terms: Lung Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Ventilator-Induced Lung Injury; Respiratory Tract Diseases; Respiration Disorders; Bronchopulmonary Dysplasia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Neurotransmitter Agents; Purinergic Antagonists; Purinergic Agents; Central Nervous System Stimulants; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Caffeine; Caffeine citrate
• Other Study ID Numbers: H-09-M-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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."
• IPD Sharing 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)
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No