Steroids and Surfactant in Extremely Low Gestation Age Infants Pilot Dose Escalation Trial
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 25
- 试验地点
- 5
- 主要终点
- Number of ELGANs With Clinical and Anti-inflammatory Efficacy of Escalating Doses of Budesonide Determined by Monitoring Respiratory Severity Score (RSS)
研究概览
简要总结
This is a phase I/II open-label study to determine the lowest, safe, effective dose of budesonide given with calfactant as the vehicle.
详细描述
This is a phase I/II open-label study to determine the lowest safe, effective dose of budesonide given with calfactant as the vehicle; the investigators will perform an unblinded dose escalation study. The investigators will administer four dosing levels of budesonide suspended in calfactant beginning with 0.025 mg/kg of budesonide administered to 8 extremely low gestational age newborns (ELGANs) who are intubated at 3-10 days of age. Daily doses (at the same dosage) will be administered to infants who remain intubated for a potential of 5 total doses in each patient. Subsequent groups of 8 infants each will receive 0.05 mg/kg, 0.10 mg/kg, and 0.15 mg/kg of budesonide in calfactant (up to 5 total doses in each patient). A total of up to 32 infants will be enrolled in the trial. The investigators will evaluate the clinical, laboratory and safety data from each group of treated infants to 28 days of age before moving to the next dosing level of budesonide.
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
- 3 Days 至 14 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •> 23 0/7 and < 27 6/7 weeks of gestational age based on center's best estimate of due date (using earliest obstetrical ultrasound, last menstrual period, examination, and other pertinent available information)
- •Day of life 3-14 from the date and time of delivery, with the date of birth being DOL 0
- •Intubated and mechanically ventilated and do not anticipate extubation in next 24 hours
排除标准
- •Serious congenital malformations or chromosomal abnormality
- •Likely to be extubated in next 24 hours
- •Clinically unstable
- •Infants who have received systemic steroids prior to dosing with study medication.
- •Infants who have received Indocin, Ibuprofen, or acetaminophen ≤ 96 hours prior to enrollment window ending
研究组 & 干预措施
0.025 mg/kg Budesonide
0.025 mg/kg Budesonide in Calfactant
干预措施: Budesonide in Calfactant (Drug)
0.050 mg/kg Budesonide
0.050 mg/kg Budesonide in Calfactant
干预措施: Budesonide in Calfactant (Drug)
0.10 mg/kg Budesonide
0.10 mg/kg Budesonide in Calfactant
干预措施: Budesonide in Calfactant (Drug)
0.15 mg/kg Budesonide
0.15 mg/kg Budesonide in Calfactant
干预措施: Budesonide in Calfactant (Drug)
结局指标
主要结局
Number of ELGANs With Clinical and Anti-inflammatory Efficacy of Escalating Doses of Budesonide Determined by Monitoring Respiratory Severity Score (RSS)
时间窗: 28 days of life for each dosing group
Dose escalation will be defined as effective at the dose level in which 5 of 8 infants achieve the following: 1. Extubation within 72 hours of first dose or after \< 3 doses-without re-intubation before 28 days of age 2. RSS on nasal continuous positive airway pressure (NCPAP) \< 1.5 or on nasal cannula Fi02 \<25% at \< 2L/min at 28 days of age, persisting for at least 72 hours. 3. Cumulative supplemental oxygen \< 4.2 from time of enrollment to 28 days of age 4 4. No respiratory support at 28 days, including no supplemental oxygen by nasal cannula AND a \> 50% suppression of the tracheal aspirate interleukin-8 (IL-8) or CCL2 (chemokine ligand 2) at 24-72 hours (or prior to extubation if occurs at \<24 hours after dosing) after the initial dose in 5 of 8 of the infants (this may be a different combination of 5 patients than those who met the above criteria).
The Clinical and Anti-inflammatory Efficacy of Escalating Doses of Budesonide Suspended in Calfactant and Given Into the Lungs of ELGANs by Monitoring Tracheal Aspirate Cytokine Levels.
时间窗: 28 days of life for each dosing group
Number of ELGANS with a clinical AND Cytokine response: a \> 50% suppression of the tracheal aspirate interleukin-8 or chemokine ligand 2 at 24-72 hours (or prior to extubation if occurs at \<24 hours after dosing) after the initial dose in 5 of 8 of the infants
次要结局
- Serial Budesonide Levels, T 1/2(At 15 minutes, 1 and 4 hours after first dose and prior to each additional dose)
- Serial Budesonide Levels, AUC(At 15 minutes, 1 and 4 hours after first dose and prior to each additional dose)
- Adverse Events/Subject Safety(Through 28 days of life)
- Serial Budesonide Levels, Peak(At 15 minutes, 1 and 4 hours after first dose and prior to each additional dose)
- Respiratory Severity Score: Mean Airway Pressure and Oxygen Requirement at 28 Days of Age(28 days of life for each dosing group)
研究者
Cynthia McEvoy
Principal Investigator, Professor of Pediatrics
Oregon Health and Science University