Pharmacokinetics and Pharmacodynamics of Budesonide With Intratracheal Surfactant (BITS) Administration in Preterm Infants < 29 Weeks Gestational Age
试验速览
- 阶段
- 1 期
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Area under the curve from serial budesonide levels
研究概览
简要总结
This is a phase I/II trial in preterm infants aimed at identifying the optimal dose of budesonide with bovine lipid extract surfactant as vehicle for intratracheal administration.
详细描述
Premature infants of gestational age less than 29 weeks with respiratory distress syndrome and clinical indication for surfactant administration will be recruited for this Phase I/II open-label study.
A total of 30 subjects will be recruited from 2 neonatal intensive care units:
- Children's Hospital-Health Sciences Centre (HSC), Winnipeg
- St. Boniface General Hospital, Winnipeg, MB
3 groups of 10 infants each will receive single dose of intratracheal budesonide (0.0625 mg/kg, 0.125 mg/kg, and 0.25 mg/kg) with BLES surfactant (5 ml/kg). PK/PD analysis will be done using clinical parameters, serum biomarkers, tracheal aspirate biomarkers and plasma budesonide levels obtained at fixed intervals.
The duration of subject participation will involve 12-17 weeks for the clinical intervention, depending on gestational age at birth and discharge date. Participants will be followed until 40 weeks or discharge, whichever comes first.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 1 Hour 至 5 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female infant born between 23 and 28+6 weeks of GA
- •Infant diagnosed with RDS according to clinical protocol criteria
- •Able to adhere to surfactant administration protocol
- •The patient is born in the study centre.
- •Subject's parent(s)/legal guardian(s) has provided signed and dated informed consent and authorization to use protected health information, as required by national and local regulations.
- •In the investigator's opinion, the subject's parent(s)/legal guardian(s) understand(s) and can comply with protocol requirements, instructions, and protocol-stated restrictions, and is likely to complete the study as planned.
排除标准
- •Older than five days at inclusion.
- •Presence of known clinically significant congenital heart disease or other major congenital malformation
- •Subjects with clinically significant laboratory abnormalities which are deemed by the investigator to represent a safety risk to participation in this study. Other laboratory parameters outside the reference range for the subject's age may be included if the investigator considers the abnormalities unlikely to introduce additional risk factors and will not interfere with data interpretation.
研究组 & 干预措施
Dosing Level 1
0.0625 mg/kg Budesonide in bovine lipid extract surfactant (BLES)
干预措施: Budesonide in bovine lipid extract surfactant (BLES) (Drug)
Dosing Level 2
0.125 mg/kg Budesonide in bovine lipid extract surfactant (BLES)
干预措施: Budesonide in bovine lipid extract surfactant (BLES) (Drug)
Dosing Level 3
0.25 mg/kg Budesonide in bovine lipid extract surfactant (BLES)
干预措施: Budesonide in bovine lipid extract surfactant (BLES) (Drug)
结局指标
主要结局
Area under the curve from serial budesonide levels
时间窗: At 24 hour time point following dosing
Blood samples will be drawn from patients to determine the serum budesonide levels to determine the area under the curve
次要结局
- Neonatal Mortality(up to 40 weeks PMA or discharge, whichever comes first)
- VentilationStrategy(till 36 weeks PMA or discharge, whichever comes first)
- Respiratory Severity Score(at baseline and till 36 weeks PMA or discharge, whichever comes first)
- Percentage of Participants with Pulmonary Hemorrhage(at baseline and 48 hours after budesonide with surfactant administration)
- Percentage of Participants with Pneumothorax on Chest X-ray(at baseline and 48 hours after budesonide with surfactant administration)
- Percentage of Participants with Necrotising Enterocolitis (NEC)(48 hours after budesonide with surfactant administration)
- Concentration of Inflammatory Biomarkers in Serum(Baseline, 24 hours, 48 hours and 1 week.)
- Bronchopulmonary Dysplasia free survival(at 36 weeks PMA or discharge, whichever comes first)
- Concentration of Inflammatory Biomarkers in Tracheal Aspirates(Baseline, 24 hours, 48 hours,1 week, 4 weeks and 36 weeks Gestational Age)
- Duration of Hospital Stay(from day 0 (birth date) to 40 weeks)
- Duration of Supplemental Oxygen(till 36 weeks PMA or discharge, whichever comes first)
- Percentage of Participants with Hypothalamic pituitary axis (HPA) suppression(at 0 and 24 hours after dosing)
- Percentage of Participants with Spontaneous Intestinal Perforation (SIP) on abdominal X-ray(at baseline and 48 hours after budesonide with surfactant administration)
- Level of Supplemental Oxygen Administered(at baseline and at 36 week Post menstrual age or discharge, whichever comes first)
- Presence of Respiratory Support(at 36 week Post menstrual age or discharge, whichever comes first)
- Percentage of Participants with Intra-ventricular Hemorrhage(at baseline and 48 hours after budesonide with surfactant administration)
- Percentage of Participants with Sepsis(at baseline and till 36 weeks PMA or discharge, whichever comes first)
- Percentage of Participants with Severe Retinopathy at Prematurity(baseline and 48 hours after budesonide with surfactant administration)