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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alveofact | Drug | Intratracheal High-dose Alveofact versus Low-dose Alveofact with or without Budesonide |
|
| 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 |
| 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 |
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Inclusion Criteria:
Gestational age ≤ 35 weeks with
Exclusion Criteria:
Preterm neonates with evidence of any of the following will be excluded:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Amira Mostafa Rashad Ibrahim | Contact | 01095420315 | 202 | Amira.Mostafa@med.asu.edu.eg |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Egypt Neonatal Intensive Care Units (NICUs), Ain Shams University Cairo, Abbasia, Egypt, 11517 | Recruiting | Cairo | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41872545 | Derived | Rashad AM, El-Khazragy N, Awad H, Gad GI, Rabie D. Dose-dependent effects of Alveofact with and without steroids on neutrophil extracellular traps in neonatal respiratory distress syndrome. Pediatr Res. 2026 Mar 23. doi: 10.1038/s41390-026-04824-9. Online ahead of print. |
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| 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. |
|
| Budesonide | Drug | Budesonide |
|
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 |
| ID | Term |
|---|---|
| D012127 | Respiratory Distress Syndrome, Newborn |
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D012128 | Respiratory Distress Syndrome |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D007235 | Infant, Premature, Diseases |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| C078272 | SF-RI 1, bovine surfactant preparation |
| D019819 | Budesonide |
| ID | Term |
|---|---|
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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