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

Phase 1RecruitingNCT06367881

Ain Shams University60 enrolled

Overview

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

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

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

Interventions

AlveofactDRUG

Intratracheal High-dose Alveofact versus Low-dose Alveofact with or without Budesonide

BudesonideDRUG

Budesonide

Eligibility

Sex: ALLMin age: 1 DayMax age: 2 Days

Medical Language ↔ Plain English

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.

Locations (1)

Egypt Neonatal Intensive Care Units (NICUs), Ain Shams University Cairo, Abbasia, Egypt, 11517

Cairo, Egypt

RECRUITING

Outcomes

Primary Outcomes

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).

Time frame: 48 hours after treatment

Secondary Outcomes

comparison of Alveolar with whole blood NET formation

Neutrophil Extracellular Trap (NET) will be extracted in alveolar fluid and compared with whole blood samples

Time frame: 48 hours

Clinical out come

Ventilation Duration in days.

Time frame: 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.

Time frame: 48 hours

oxygen needs

FIO2 percentage on invasive and non-invasive respiratory support.

Time frame: 1 month

Hospital stay

Duration of NICU stay will be recorded in Days.

Central Contacts

Amira Mostafa Rashad Ibrahim

CONTACT

01095420315 Amira.Mostafa@med.asu.edu.eg

Data from ClinicalTrials.gov

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