Assessment Of Dose-Dependent Immunomodulatory Effect Of Alveofact With or Without Steroisd In Neonatal RDS

Ain Shams University

Status and phase: Enrolling; Phase 1

Conditions: Neutrophil Extracellular Trap Formation; Inflammatory Response; Neonatal Respiratory Distress Syndrome; Premature Lungs; Preterm Birth

Treatments: Drug: Budesonide; Drug: Alveofact

Study type: Interventional

Funder types: Other

Identifiers

NCT06367881

MD 185/ 2022

Details and patient eligibility

About

An Exploratory Randomized double-arm controlled trial to evaluate the immunomodulatory effect of low versus high dose of Alveofact with or without Budesonide.

Full description

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 1 to 2 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Gestational age ≤ 35 weeks with

  1. Respiratory distress syndrome.
  2. Need surfactant administration based on European RDS consensus: (Sweet et al., 2019)
  3. If intubation is required as part of stabilization.
  4. Clinically presenting with increased work of breathing including (tachypnea, nasal flaring, grunting, retractions, and cyanosis, with decreased air entry on auscultation.
  5. Babies who are worsening when FiO2 >0.30 on CPAP pressure of at least 6 cm H2O to maintain normal saturations.

Exclusion criteria

Preterm neonates with evidence of any of the following will be excluded:

1. Chromosomal anomaly or Congenital heart defect
2. Hemodynamically significant patent ductus arteriosus.
3. Early-onset sepsis or bacterial infection
4. Congenital pneumonia
5. Intra ventricular hemorrhage (IVH)
6. Parenteral refusal to participate.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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60 participants in 4 patient groups

Group 1: Low dose Alveofact without steroids

Active Comparator group

Description:

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.

Treatment:

Drug: Alveofact

Group 2: Low dose Alveofact with steroids

Experimental group

Description:

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.

Treatment:

Drug: Budesonide

Drug: Alveofact

Group 3: High dose Alveofact without steroids

Active Comparator group

Description:

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.

Treatment:

Drug: Alveofact

Group 4: Group 1: High dose Alveofact with steroids

Experimental group

Description:

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.

Treatment:

Drug: Budesonide

Drug: Alveofact