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

NCT06367881 | Recruiting Phase 1

• 1 other identifier: MD 185/ 2022
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• comparison of Alveolar with whole blood NET formation

  48 hours

• Clinical out come

  1 month

• Assessment of Reactive Oxygen Species (ROS)

  48 hours

• oxygen needs

  1 month

• Hospital stay

  1 month

Study Arms (4)

Group 1: Low dose Alveofact without steroids

ACTIVE COMPARATOR

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

Group 2: Low dose Alveofact with steroids

EXPERIMENTAL

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; Drug: Budesonide

Group 3: High dose Alveofact without steroids

ACTIVE COMPARATOR

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

Group 4: Group 1: High dose Alveofact with steroids

EXPERIMENTAL

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; Drug: Budesonide

Interventions

Alveofact DRUG

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

Group 1: Low dose Alveofact without steroids; Group 2: Low dose Alveofact with steroids; Group 3: High dose Alveofact without steroids; Group 4: Group 1: High dose Alveofact with steroids

Budesonide DRUG

Budesonide

Group 2: Low dose Alveofact with steroids; Group 4: Group 1: High dose Alveofact with steroids

Eligibility Criteria

• Age: 1 Day - 2 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

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

Cairo, Egypt

RECRUITING

MeSH Terms

Conditions

Respiratory Distress Syndrome, Newborn; Premature Birth

Interventions

SF-RI 1, bovine surfactant preparation; Budesonide

Condition Hierarchy (Ancestors)

Respiratory Distress Syndrome; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Central Study Contacts

Amira Mostafa Rashad Ibrahim

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer

Study Record Dates

• First Submitted: April 7, 2024
• First Posted: April 16, 2024
• Study Start: August 18, 2022
• Primary Completion: July 1, 2024
• Study Completion: October 1, 2024
• Last Updated: April 16, 2024

Record last verified: 2024-04

Locations

EG (1)