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

Phase 2

Recruiting

• Conditions: Prematurity; Respiratory Disease; Ventilator Lung; Newborn
• Interventions: Drug: Caffeine citrate; Other: Placebo

• Registration Number: NCT06026163
• Lead Sponsor: Ministry of Health, Saudi Arabia

Brief 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.

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 Timeline

• Study First Submitted: 2023-08-27
• Study First Submitted QC: 2023-09-03
• Study First Posted: 2023-09-06
• Study Start: 2023-10-12
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-01
• Last Update Posted: 2025-01-03
• Primary Completion: 2027-10-30
• Study Completion: 2028-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 134

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Caffeine citrate group	Caffeine citrate	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).
Control group	Placebo	Infants received equivalent volume of saline.

Primary Outcome Measures

Name	Time	Method
Duration of respiratory support	28 days	cumulative duration of mechanical ventilation, non-invasive positive pressure ventilation and nasal cannula therapy (days)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

King Salman Bin Abdulaziz Medical City; 🇸🇦 Medina, Saudi Arabia