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

Preterm Birth Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06367881
• Other study ID #: MD 185/ 2022
• Status: Recruiting
• Phase: Phase 1
• Start date: August 18, 2022
• Est. completion date: October 2024

Study information

• Verified date: April 2024
• Source: Ain Shams University
• Contact: Amira Mostafa Rashad Ibrahim
• Phone: 01095420315
• Email: Amira.Mostafa[@]med.asu.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 2 Days

Eligibility

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.

Related Conditions & MeSH terms

• Hyaline Membrane Disease
• Inflammatory Response
• Neonatal Respiratory Distress Syndrome
• Neutrophil Extracellular Trap Formation
• Premature Birth
• Premature Lungs
• Preterm Birth
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• Alveofact
Intratracheal High-dose Alveofact versus Low-dose Alveofact with or without Budesonide
• Budesonide
Budesonide

Locations

Country	Name	City	State
Egypt	Egypt Neonatal Intensive Care Units (NICUs), Ain Shams University Cairo, Abbasia, Egypt, 11517	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Clinical out come	Ventilation Duration in days.	1 month
Secondary	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
Secondary	oxygen needs	FIO2 percentage on invasive and non-invasive respiratory support.	1 month
Secondary	Hospital stay	Duration of NICU stay will be recorded in Days.	1 month