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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Prematurity, Respiratory Disease, Ventilator Lung; Newborn

Intervention / Treatment
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* Drug: Caffeine citrate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 3 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Caffeine citrate group<br>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<br>* 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)<br>* Other names: Intervention group;|
| Placebo Comparator: Control group<br>Infants received equivalent volume of saline. | Other: Placebo<br>* Equivalent volume of saline<br>* Other names: Saline;|

What is the study measuring?
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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 |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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caffeine, preterm, newborn, respiratory support