Different Doses Domperidone In The Short-term Treatment Of Feeding Intolerance In Premature Infants:A Multi-Center Randomized Controlled Clinical Trials

1.Research BackgroundWe urgently need an objective,immediate,accurate,non-invasive,portable-operational evaluation model to describe feeding intolerance.Then the model can help the further research and treatment.The medicines and healthcare products regulatory agency issued a safety warning of domperidone in May 2012 and limited its indications.But there are still many clinical practicers use domperidone in the treatment of upper gastrointestinal motility dysfunction in children or infantsThe effective dose of domperidone is not the same in the clinical work.We will discuss the 0.2mg/kg/tds and 0.4mg/kg/tds and 0.6mg/kg/tds domperidone for the treatment of feeding intolerance in preterm infants.Oral domperidone has minimal complications.Some studies have reported the prolonged QTc interval with domperidone.We also compared the QTc interval before and after the domperidone treatment.2.Research Purposes:2.1 To detect a proper model for feeding intolerance;2.2 To conduct a multi-center,large sample,randomized,controlled,double-blind,prospective research to find out the best effective dose of domperidone for the treatment of feeding intolerance in preterm infants.2.3 To find out the change of QTc interval in premature infants who take the domperidone treatment.3.Study Design3.1 research objects and groups3.1.1 Inclusion Criteria:<34 weeks premature infant;percentage of test meal residual>55%.3.1.2 Finished Criteria:percentage of test meal residual<55%.3.2 Group Definition3.2.1:This study included three experimental group and the placebo control group.The dose of treatment group contained 0.2mg/kg/tds,0.4mg/kg/tds,0.6mg/kg/tds.Each treatment group included in 37,24,25 premature infants respectively.Placebo group included 22 premature infants.The total premature infants was 108 people.4.Assessment Criteria:4.1 The main assessment criteria:0.5h test meal residual percentage;3h gastric residual milk percentage;maximum QTc interval before medication;maximum QTc interval after treatment;4.2 Secondary assessment criteria:The total time of domperidone treatment;The amout of daily oral intake of preterm infant;The total duration of hospitalization;The time to achieve full enteral feeding;5.Results5.1 The effectiveness of the model:the p value of the inclusion criteria,the finished criteria and the trend comparing the designed model and the actual feeding situation were 0.317,0.209,0.132,respectively.5.2 The demographic data:the birth weight,gestational age and gender were not statistically different.5.3 The p value of the success rate comparing between the three different dose of domperidone treatment and the placebo group were 0.69,0.219,0.35,respectively.And this means neither dose of domperidone have enough effectiveness.5.4 There were no statistical difference of QTc interval before and after treatment in the the placebo group,0.4mg/kg/tds group,0.6mg/kg/tds group.The QTc interval have no significant difference before and after treatment in three groups.But the p value comparing before and after treatment of 0.2mg/kg/tds domperidone was 0.015,less than 0.05,which means the QTc interval was significantly shorter after treatment.But the QTc interval shorten had no clinical meaning.We could conclude that short term usage of domperidone would not cause QTc interval prolongation.5.5 The daily 0.5h test meal residual percentage,the daily 3h gastric residual milk residual percentage,the total duration of hospitalization and the time to achieve the total gastrointestinal feeding between each group had no significant difference.6.Conclusion:6.1 This study have successfully designed a test model calculating 0.5h test meal residual percentage to demostrate the feeding intolerance.6.2 There was no significant difference in the success rate for feeding intolerance treatment in preterm infants between three treatment group and placebo group.6.3 The 0.4mg/kg/tds group has the best effectiveness in the treatment of feeding intolerance;6.4 There was no difference in the time to achieve total enteral feeding and the total duration of hospitalization.6.5 The effectiveness in the 0.6mg/kg/tds group varied differently.6.6 In a short term treatment of three different doses domperidone have no change in QTc interval in preterm infants.6.7 All premature infants in the experimental group found no adverse reactions caused by domperidone suspension solution.