Randomized controlled trial (RCT) comparing between High versus Standard dose caffeine citrate for apnoea in prematurity

Name : Comparing between High dose caffeine (Arm 1) and standard dose caffeine (Arm 2) Why : Available literatures regarding high versus standard/low dose caffeine for Apnoea in prematurity is not conclusive due to heterogeneity of the doses, gestational age, indication of starting caffeine and sample size. However, some data suggest that the high dose caffeine is beneficial without causing adverse effects except for mild tachycardia. The reason of conducting the study is to determine the efficacy and safety of a high dose of caffeine compared to standard dose for the prevention of apnoea in prematurity WHAT Materials : All the research tools that will be used in the study is routinely used for premature babies in Neonatal Intensive Care Unit (NICU). All the research tools have been proved its safety and reliability. Infant’s oxygen saturation, heart rate, and respiratory rate are continuously monitored using monitor that is available in NICU. Blood pressure will be checked, indirectly by oscillometry or Intra-arterial blood pressure if patient is on arterial line. Procedures : Before premature delivery and subject recruitment, medical officer or specialist will be subjected to do prenatal counselling to the mothers in antenatal ward HUSM. During the counselling, the study will be briefly explained to the mother in order to give them an ample time to think whether wants to include in the study or not. Premature babies who fulfill inclusion and exclusion criteria will be assigned randomly into either two groups (Group A: High dose group, Group B: Standard dose group). Infants in group A will receive high dose oral caffeine citrate (loading dose of 40 mg/kg/day equivalent to 20 mg /kg/day of caffeine base and maintenance dose of 20 mg/kg/day equivalent to 10 mg /kg/day of caffeine base). Maintenance dose will be given 24 hours after loading. Infants in group B will receive standard dose oral caffeine citrate (loading dose of 20 mg/kg/day equivalent to 10mg/kg/day of caffeine base and maintenance dose of 10mg/kg/day equivalent to 5 mg/kg/day of caffeine base) Oral caffeine loading dose will be given to the allocation group (Group A and Group B) within 24 hours periextubation period. If the patient is not intubated, oral caffeine loading dose will be given immediately. If patient has failure extubation, caffeine will be off and continue ventilation. Sameh Mohammed et al defined failure extubation as requiring reintubation within 72 hours. If successful extubation, maintenance dose (MD) will be continued 24 hours after starting caffeine and continue on daily basis. If patient has feeding intolerance while the patient is on caffeine, the medication will be changed into intravenous aminophylline. Previous oral caffeine dose will be restarted once feeding intolerance resolved. The duration of oral caffeine will be continued at least corrected gestational age is 34 weeks after been assessed by trained doctor. Oral caffeine will be continued beyond 34 weeks gestational age if indicated and assigned by doctor. The study will be conducted in Neonatal Intensive Care Unit, Hospital USM, Kubang Kerian Kelantan,Malaysia. The hospital is a teaching hospital for University Sains Malaysia and this is where the Health Campus located. Kubang Kerian is one of the major towns of Kelantan, a state in Malaysia where majority of its population are Malays from different socio-economic background. The Neonatal Intensive Care Unit provides level 1 to level 4 intensive care to neonate patient and received referral from all parts of Kelantan and all over the country The Primary Investigator will monitor the study monthly and fill the data in proforma.