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

Assessment Of Dose-Dependent Immunomodulatory Effect Of Intratracheal Alveofact With Or Without Local Steroids In Respiratory Distress Syndrome Of Preterm Neonates

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

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Response; Preterm Birth; Premature Lungs; Neonatal Respiratory Distress Syndrome; Neutrophil Extracellular Trap Formation
• Intervention / Treatment: Drug: Alveofact; Drug: Budesonide

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amira Mostafa Rashad Ibrahim; Phone Number: 202 01095420315; Email: Amira.Mostafa@med.asu.edu.eg

Study Locations

• Egypt
  • Cairo, Egypt
    • Recruiting
    • Egypt Neonatal Intensive Care Units (NICUs), Ain Shams University Cairo, Abbasia, Egypt, 11517
    • Contact: Ain Shams University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Alveofact; Intratracheal High-dose Alveofact versus Low-dose Alveofact with or without Budesonide
Experimental: 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.	Drug: Alveofact; Intratracheal High-dose Alveofact versus Low-dose Alveofact with or without Budesonide; Drug: Budesonide; Budesonide
Active Comparator: 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.	Drug: Alveofact; Intratracheal High-dose Alveofact versus Low-dose Alveofact with or without Budesonide
Experimental: 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.	Drug: Alveofact; Intratracheal High-dose Alveofact versus Low-dose Alveofact with or without Budesonide; Drug: Budesonide; Budesonide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Neutrophil Extracellular Trap (NET)	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).	48 hours after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
comparison of Alveolar with whole blood NET formation	Neutrophil Extracellular Trap (NET) will be extracted in alveolar fluid and compared with whole blood samples	48 hours
Clinical out come	Ventilation Duration in days.	1 month
Assessment of Reactive Oxygen Species (ROS)	the lipid peroxidation will be calorimetrically measured using thiobarbituric acid (TBA) reactive compounds such as malondialdehyde (MDA) in microplates at 532 nm.	48 hours
oxygen needs	FIO2 percentage on invasive and non-invasive respiratory support.	1 month
Hospital stay	Duration of NICU stay will be recorded in Days.	1 month

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2022
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: April 7, 2024
• First Submitted That Met QC Criteria: April 15, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Infant, Premature, Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Syndrome; Premature Birth; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Hyaline Membrane Disease; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: MD 185/ 2022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No