Assessment Of Dose-Dependent Immunomodulatory Effect Of Intratracheal Alveofact With Or Without Local Steroids In Respiratory Distress Syndrome Of Preterm Neonates
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Assessment of Neutrophil Extracellular Trap (NET)
研究概览
简要总结
An Exploratory Randomized double-arm controlled trial to evaluate the immunomodulatory effect of low versus high dose of Alveofact with or without Budesonide.
详细描述
Neonatal respiratory distress syndrome (RDS) is caused by lung immaturity and surfactant deficiency in preterm newborns and is an important cause of morbidity and mortality.
Surfactant therapy plays an essential role in the management of RDS as it reduces lung injury and improves survival, While surfactant alone is very effective, some studies showed that its combination with budesonide significantly reduces BPD and inflammatory markers.
Neutrophils extracellular traps (NETs) are a defense mechanism where neutrophils are the reaction to microbial infection and cast a net-like structure. NETs are composed of chromatin decondensed and some 30 enzymes and peptides. Many components such as Neutrophil elastase (NE) and Myeloperoxidase enzyme (MPO) have antimicrobial, but also a cytotoxic property that causes tissue injury. The immune regulatory abilities of the pulmonary surfactant are known to alter the function of the adaptive and innate immune cells.
So, in this study, The Investigator will Assess the immunomodulatory effect of low and high doses of Alveofact with or without Budesonide.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 1 Day 至 2 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gestational age ≤ 35 weeks with
- •Respiratory distress syndrome.
- •Need surfactant administration based on European RDS consensus: (Sweet et al., 2019)
- •If intubation is required as part of stabilization.
- •Clinically presenting with increased work of breathing including (tachypnea, nasal flaring, grunting, retractions, and cyanosis, with decreased air entry on auscultation.
- •Babies who are worsening when FiO2 >0.30 on CPAP pressure of at least 6 cm H2O to maintain normal saturations.
排除标准
- •Preterm neonates with evidence of any of the following will be excluded:
- •Chromosomal anomaly or Congenital heart defect
- •Hemodynamically significant patent ductus arteriosus.
- •Early-onset sepsis or bacterial infection
- •Congenital pneumonia
- •Intra ventricular hemorrhage (IVH)
- •Parenteral refusal to participate.
研究组 & 干预措施
Group 1: Low dose Alveofact without steroids
After obtaining parental consent, preterm neonates diagnosed with respiratory distress syndrome will be randomly administered a low dose of Intratracheal Alveofact (50 mg/kg) once without Budesonide. The clinical improvement of ventilatory settings, oxygen requirement, Assessment of Neutrophil Extracellular Trap (NET) formation, and Reactive Oxygen Species (ROS) will then be assessed before and 48 hours after treatment.
The patient who will receive low-dose alveofact retreatment will be considered if the fraction of inspired oxygen (FiO2) was > 0.4 (does 50 mg/kg birth weight) 6 hours after treatment.
干预措施: Alveofact (Drug)
Group 2: Low dose Alveofact with steroids
After obtaining parental consent, preterm neonates diagnosed with respiratory distress syndrome will be randomly administered a low dose of Intratracheal Alveofact (50 mg/kg) once with Budesonide (0.25 mg/kg). The clinical improvement of ventilatory settings, oxygen requirement, Assessment of Neutrophil Extracellular Trap (NET) formation, and Reactive Oxygen Species (ROS) will then be assessed before and 48 hours after treatment.
The patient who will receive low-dose alveofact retreatment will be considered if the fraction of inspired oxygen (FiO2) was > 0.4 (does 50 mg/kg birth weight) 6 hours after treatment.
干预措施: Alveofact (Drug)
Group 2: Low dose Alveofact with steroids
After obtaining parental consent, preterm neonates diagnosed with respiratory distress syndrome will be randomly administered a low dose of Intratracheal Alveofact (50 mg/kg) once with Budesonide (0.25 mg/kg). The clinical improvement of ventilatory settings, oxygen requirement, Assessment of Neutrophil Extracellular Trap (NET) formation, and Reactive Oxygen Species (ROS) will then be assessed before and 48 hours after treatment.
The patient who will receive low-dose alveofact retreatment will be considered if the fraction of inspired oxygen (FiO2) was > 0.4 (does 50 mg/kg birth weight) 6 hours after treatment.
干预措施: Budesonide (Drug)
Group 3: High dose Alveofact without steroids
After obtaining parental consent, preterm neonates diagnosed with respiratory distress syndrome will be randomly administered a High dose of Intratracheal Alveofact (100 mg/kg) once without Budesonide. The clinical improvement of ventilatory settings, oxygen requirement, Assessment of Neutrophil Extracellular Trap (NET) formation, and Reactive Oxygen Species (ROS) will then be assessed before and 48 hours after treatment.
干预措施: Alveofact (Drug)
Group 4: Group 1: High dose Alveofact with steroids
After obtaining parental consent, preterm neonates diagnosed with respiratory distress syndrome will be randomly administered a High dose of Intratracheal Alveofact (100 mg/kg) once with Budesonide(0.25 mg/kg). The clinical improvement of ventilatory settings, oxygen requirement, Assessment of Neutrophil Extracellular Trap (NET) formation, and Reactive Oxygen Species (ROS) will then be assessed before and 48 hours after treatment.
干预措施: Alveofact (Drug)
Group 4: Group 1: High dose Alveofact with steroids
After obtaining parental consent, preterm neonates diagnosed with respiratory distress syndrome will be randomly administered a High dose of Intratracheal Alveofact (100 mg/kg) once with Budesonide(0.25 mg/kg). The clinical improvement of ventilatory settings, oxygen requirement, Assessment of Neutrophil Extracellular Trap (NET) formation, and Reactive Oxygen Species (ROS) will then be assessed before and 48 hours after treatment.
干预措施: Budesonide (Drug)
结局指标
主要结局
Assessment of Neutrophil Extracellular Trap (NET)
时间窗: 48 hours after treatment
Neutrophil Extracellular Trapformation in neutrophil granulocytes as an evaluation of the therapeutic effect of two different doses of Alveofact with and without Steroids in Neonatal respiratory distress syndrome. Isolation of Neutrophil granulocytes from Bronchoalveolar fluid and whole blood samples using Neutrophil-specific magnetic beads. The purity and number of extracted neutrophils will be validated by cell morphology in hematoxylin-eosin staining and fluorescence-activated cell sorting for anti-CD-15 monoclonal antibodies. Assessment of Neutrophil Extracellular Trap (NET) formation: The amount of NET will be quantified by three different assays including; (1): measurement of neutrophil-specific Myeloperoxidase activity, (2): Neutrophil-elastase activity, and (3): Neutrophil-specific cell-free DNA (cfDNA).
次要结局
- Clinical out come(1 month)
- Assessment of Reactive Oxygen Species (ROS)(48 hours)
- oxygen needs(1 month)
- comparison of Alveolar with whole blood NET formation(48 hours)
- Hospital stay(1 month)
研究者
Amira Mostafa Rashad ibrahim
Assistant Lecturer
Ain Shams University