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

NCT ID: NCT06367881

Last Updated: 2024-04-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-18
• Study Completion Date: 2024-10-31

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.

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Alveofact

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Alveofact

Intervention Type: DRUG

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

Budesonide

Intervention Type: DRUG

Budesonide

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.

Group Type: ACTIVE_COMPARATOR

Alveofact

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Alveofact

Intervention Type: DRUG

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

Budesonide

Intervention Type: DRUG

Budesonide

Interventions

Alveofact

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

Intervention Type: DRUG

Budesonide

Budesonide

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 2 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Amira Mostafa Rashad ibrahim

Assistant Lecturer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

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

Cairo, , Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Amira Mostafa Rashad Ibrahim

Role: CONTACT

Amira.Mostafa@med.asu.edu.eg

01095420315 ext. 202

Facility Contacts

Ain Shams University

Role: primary

Other Identifiers

MD 185/ 2022

Identifier Type: -

Identifier Source: org_study_id