Kim, Sang Bum
(Department of Pediatrics, Ajou University School of Medicine)
,
Lee, Jang Hoon
(Department of Pediatrics, Ajou University School of Medicine)
,
Lee, Juyoung
(Department of Pediatrics, Seoul National University College of Medicine)
,
Shin, Seung Han
(Department of Pediatrics, Seoul National University College of Medicine)
,
Eun, Ho Sun
(Department of Pediatrics, Yonsei University College of Medicine)
,
Lee, Soon Min
(Department of Pediatrics, Yonsei University College of Medicine)
,
Sohn, Jin A
(Department of Pediatrics, Seoul National University College of Medicine)
,
Kim, Han Suk
(Department of Pediatrics, Seoul National University College of Medicine)
,
Choi, Byung Min
(Department of Pediatrics, Korea University Ansan Hospital)
,
Park, Min Soo
(Department of Pediatrics, Yonsei University College of Medicine)
,
Park, Kook In
(Department of Pediatrics, Yonsei University College of Medicine)
,
Namgung, Ran
(Department of Pediatrics, Yonsei University College of Medicine)
,
Park, Moon Sung
(Department of Pediatrics, Ajou University School of Medicine)
Purpose: The purpose of this study was to evaluate the efficacy and safety of Montelukast sodium in the prevention of bronchopulmonarydysplasia (BPD). Methods: The Interventional study was designed as a multicenter, prospective, and randomized trial, with open labeled and parallel-experimental group...
Purpose: The purpose of this study was to evaluate the efficacy and safety of Montelukast sodium in the prevention of bronchopulmonarydysplasia (BPD). Methods: The Interventional study was designed as a multicenter, prospective, and randomized trial, with open labeled and parallel-experimental groups, 66 infants were enrolled and allocated to either the case group (n=30) or the control group (n=36) based on gestational age (GA). Infants in the case group were given Montelukast sodium (Singulair) based on their body weight (BW). Zero week was defined as the start time of the study. Results: The incidence of moderate to severe BPD was not different between the groups (case group: 13 of 30 [43.3%] vs. control group: 19 of 36 [52.8%], P=0.912). Additionally, secondary outcomes such as ventilation index, mean airway pressure and resort to systemic steroids were not significantly different. There were no serious adverse drug reactions in either group, and furthermore the rate of occurrence of mild drug related-events were not significantly different (case group: 10 of 42 [23.8%] vs. control group: 6 of 48 (15.8%), P=0.414). Conclusion: Montelukast was not effective in reducing moderate or severe BPD. There were no significant adverse drug events associated with Montelukast treatment.
Purpose: The purpose of this study was to evaluate the efficacy and safety of Montelukast sodium in the prevention of bronchopulmonarydysplasia (BPD). Methods: The Interventional study was designed as a multicenter, prospective, and randomized trial, with open labeled and parallel-experimental groups, 66 infants were enrolled and allocated to either the case group (n=30) or the control group (n=36) based on gestational age (GA). Infants in the case group were given Montelukast sodium (Singulair) based on their body weight (BW). Zero week was defined as the start time of the study. Results: The incidence of moderate to severe BPD was not different between the groups (case group: 13 of 30 [43.3%] vs. control group: 19 of 36 [52.8%], P=0.912). Additionally, secondary outcomes such as ventilation index, mean airway pressure and resort to systemic steroids were not significantly different. There were no serious adverse drug reactions in either group, and furthermore the rate of occurrence of mild drug related-events were not significantly different (case group: 10 of 42 [23.8%] vs. control group: 6 of 48 (15.8%), P=0.414). Conclusion: Montelukast was not effective in reducing moderate or severe BPD. There were no significant adverse drug events associated with Montelukast treatment.
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제안 방법
Based on this, covariate analyses like age, weight, and sex were added. The evaluation of the developed model was done by three methods: (1) relative standard error (standard error/estimate value) where sensitivity of parameter estimate value less than 50% is reliable, (2) visual inspection 1: comparison of similarity between longitudinal progress of the predicted value and observed value, (3) visual inspection 2: in the group of individual, evaluate bias whether weighted residual is distributed around a line of zero (weighted residual=residual/observed value).
The safety of the drug evaluation was performed by Fisher exact test comparing the incidence and severity of adverse reaction, as well as causality of adverse with drug administration, between two groups. Vital signs, physical examinations, and laboratory results are evaluated by descriptive statistic comparisons between two groups.
, but it had small population and retrospective design. Therefore we performed this study in order to determine the efficacy and safety of Montelukast on BPD in preterm infants, with prospective, randomized trial.
This study was a multicenter, prospective, randomized, open labeled, parallel group, intervention trial. All protocols were approved by the Institutional Review Board at each site, and the studies were conducted in compliance with the Korea Food and Drug Administration.
대상 데이터
A total of 83 infants enrolled in 5 units, but only 77 infants constituted the study group; 1 infant was excluded due to lack of parental consent, 1 infant based on exclusion criteria, 1 infant due to excess number, and 3 infants for violation of medication protocol. Among the 77 infants, 37 enrolled in the case group and 40 in the control group.
All clinical assessments and data collections were performed prospectively by local investigators, who were all trained pediatricians. The evaluation of data included: (1) efficacy of the drug, (2) safety of the drug, and (3) pharmacokinetic evaluation.
A total of 83 infants enrolled in 5 units, but only 77 infants constituted the study group; 1 infant was excluded due to lack of parental consent, 1 infant based on exclusion criteria, 1 infant due to excess number, and 3 infants for violation of medication protocol. Among the 77 infants, 37 enrolled in the case group and 40 in the control group. 7 infants of the case group were terminated early; 3 infants were excluded for onset of comorbidity; 1 infant for treatment with phenobarbital; 1 infant for the lack of parental consent; 1 infant for protocol violation; 1 infant based on the researcher’s opinion.
Seven infants from 3 units enrolled to the pharmacokinetic study. Among 17 infants, 9 enrolled in the single dose group and 8 in the multiple dose group.
Concentration of Montelukast over time. Seventeen infants in 3 NICU, enrolled in the pharmacokinetic study. They were also divided at each center, according to sampling time.
데이터처리
1 (R Foundation for Statistical Computing, Vienna, Austria) was used for primary outcome. The secondary efficacy rating variables between two groups are done by t test and Fisher exact test. The t test was used for ventilation index and mean airway pressure.
성능/효과
They reported the combination of death and BPD (BPD/death) between inhaled nitric oxide and control groups, and the proportion of the BPD/death of control group was 90%. Based on these data, we assumed that the difference of morbidity and mortality of BPD between two groups is 40%, and the rate of morbidity and mortality of BPD is 90%. Accordingly, statistical power 80%, type I error 0.
In conclusion, Montelukast was not effective in reducing the moderate or severe BPD. Additionally, there was no significant increase in adverse drug event associated with Montelukast treatment.
However, most of the adverse reactions were evaluated as unlikely to be causally related to Montelukast treatment (data not shown). The laboratory findings demonstrated that the number of clinically significant (CS) abnormal platelet count was increased significantly in the case group (case group: 6 vs. control group: 1, P=0.043), while the number of nonclinically significant (NCS) abnormal platelet count was increased in the control group rather than case group. There were no significant differences between groups in the other laboratory findings (Table 5).
21) with incidence confirmed at 40%. They reported the combination of death and BPD (BPD/death) between inhaled nitric oxide and control groups, and the proportion of the BPD/death of control group was 90%. Based on these data, we assumed that the difference of morbidity and mortality of BPD between two groups is 40%, and the rate of morbidity and mortality of BPD is 90%.
후속연구
Nevetheless, this study is significant in that it is a first prospective study of Montelukast for preterm infant. Based on designing and finding from the present study, it is expected that further studies are needed on the relationship between BPD and leukotriene modifiers.
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