Caffeine as Respiratory Stimulant in Preterm Infants

Study Overview
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Brief Summary
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comparison between rate of occurance of apnea of prematurity AOP when using high and low dose caffeine

Detailed Description
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Caffeine is one of the widely used medications in the neonatal care units and in spite of its widespread use in preterm infants, there has been little information about the optimal efficient dose in those patients Caffeine therapy for treatment of apnea of prematurity (AOP) is well established over the past few years, yet the optimal loading and maintenance dose of caffeine in preterm infants is not well-studied AOP is a common complication of preterm birth, which affects more than 80 % of neonates with a birth weight less than 1,000 g. Methylxanthine (MGs), including caffeine and theophylline, are a mainstay in the treatment and prevention of AOP The efficiency of caffeine, as a preferred methylxanthine, to stimulate respiration has been well proven as it has a significant favorable impact on neonatal morbidity as bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA) ligation. Also, the results of previous studies revealed that caffeine enhances respiratory muscle strength and lung function followed by easier weaning of mechanical ventilation in premature infants. Besides, a rapid and sustained increase in diaphragmatic activity and tidal volume was reported in preterm infants followed by caffeine administration Previous studies have shown that caffeine citrate was generally well tolerated by premature neonates in clinical trials and declined the incidence of apnea in this population compared with placebo. Also, caffeine is related to superior outcomes due to its lower toxicity and it is a preferred drug for apnea in preterm infants with respiratory problems. It has also a significant function as a noninvasive respiratory support. It facilitates the transition from invasive to noninvasive support, reduces the duration of positive airway pressure support and decreases the risk of BPD in preterm infants The optimum caffeine dose in preterm infants with AOP has not been well studied as well as heterogeneous reports on the optimal loading and maintenance dose of caffeine in several studies in terms of benefits and risks. Many investigations have been conducted about various dosing regimens in the improvement or prevention of respiratory disorders of premature infants. These dosage regimens, although, have been associated with varying degrees of success The aim of this study is to determine if the use of caffeine in doses higher than the currently standard dose can decrease the frequency of apnea in preterm infants without causing significant side effects

Official Title
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High Versus Low Dose Caffeine as Respiratory Stimulant in Preterm Infants

Conditions
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Apnea of Prematurity

Intervention / Treatment
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* Drug: Caffeine Citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Preterm infants with a gestational age <32 weeks in room air or CPAP (prophylactic). Preterm infants with gestational age 32-34 weeks who exhibited apnea of prematurity within the first 10 days of life in room air or CPAP Exclusion Criteria: • Major congenital malformations. Chromosomal anomalies. Preterm infants on mechanical ventilation. Preterm infants on NIPPV.

Ages Eligible for Study
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Maximum Age: 10 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The current study will be carried on preterm infants admitted to the Neonatal Intensive Care Unit (NICU), Ain Shams University 80 Patients divided into two groups each group will contain 40 subjects Group sample sizes of 40 and 40 achieve 83% power to detect a difference of -7.0 regarding frequency of apnea attacks between the null hypothesis that both group means are 9.0 and the alternative hypothesis that the mean of group 2 is 16.0 with known group standard deviations of 3.7 and 5.2 and with a significance level (alpha) of 0.05000 using a two-sided Mann-Whitney test assuming that the actual distribution is uniform
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Dose arm<br>subjects will receive the high dose of the drug | Drug: Caffeine Citrate<br>* study rate of occurrence of Apnea of Prematurity between the 2 groups<br>|
| Active Comparator: low dose arm<br>subject will receive low dose of the drug | Drug: Caffeine Citrate<br>* study rate of occurrence of Apnea of Prematurity between the 2 groups<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High Versus Low Dose Caffeine as Respiratory Stimulant in Preterm Infants | assess occurrence of apnea of prematurity between infants receiving high and low dose caffeine | baseline |