Clinical trial NCT03485703: Azithromycin in the Prevention of Lung Injury in Premature Newborn
Official title: Randomized Clinical Trial: Use of Azithromycin to Prevent Lung Damage in Preterm Newborns Under Mechanical Ventilation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bronchopulmonary Dysplasia
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
First posted: 2018-04-02
Enrollment: 80
Sex: ALL
Minimum age (years): 1
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: for a period of 5 days, a group of infants will receive azithromycin EV at a dose of 10 mg / kg / day and another group will receive placebo (SF 0.9%) in the same volume, every 24 hours.
Primary purpose: PREVENTION

Brief summary: The introduction of invasive mechanical ventilation in the treatment of preterm infants works as an adjuvant in the treatment of acute respiratory failure, which has resulted in significantly significant survival rates. In recent years there has been an increase in the number of evidence that mechanical factors can cause lung injury through inflammatory cells and soluble mediators.

The alveolar and airway epithelium is an important source of cytokine release. Cytokines are very low molecular weight proteins or glycoproteins with hormone-like actions. They contribute to the pathogenesis of various diseases through the ability to induce other inflammatory mediators Mechanical ventilation strategies can increase pulmonary and systemic cytokines and lead to dysfunction of multiple organs and systems.

Azithromycin has a potent anti-inflammatory and immunomodulatory effect It suppresses the production of proinflammatory cytokines (IL-6, IL-1, and TNF-α), has effective antimicrobial properties against Ureaplasma and, best of all, few side effects The hypothesis of this study is that azithromycin would reduce pulmonary inflammation induced by mechanical ventilation in premature infants, conferring a protective character.Randomized clinical trial: use of azithromycin in preventing pulmonary damage newborn preterm undergoing mechanical ventilation

Detailed description: The nature of lung injury induced by mechanical ventilation is clearly established, including the release of immunoinflammatory mediators. However, safe drug therapy that decreases its severity is not available. Azithromycin is a macrolide antibiotic with potent anti-inflammatory effects, but has been poorly studied in preterm infants except for very few studies in extreme preterms for the prevention of bronchopulmonary dysplasia.

The aim of this study was to evaluate the effect of azithromycin on the prevention of cytokine-mediated MV-induced injury in cytokine plasma levels (IL-1β, IL-2, IL-6, IL-8, IL-10 and TNF- α) in preterm newborns, submitted to mechanical ventilation in the first 72 hours of life.

It is a double-blind placebo controlled clinical trial. When the use of azithromycin was considered, after signing the informed consent, a randomization was performed by the intravenous mixtures center of Hospital de clinicas de porto alegre where a group of newborns will receive azithromycin EV at the dose of 10mg / kg / day and another group will receive placebo (SF 0.9%) in the same volume, a blood aliquot of 300μL will be collected in all ETDA for cytokine analysis and PCR for Ureaplasma. After 5 days of starting azithromycin or placebo, a new sample will be collected for cytokines along with blood collection from the patient's routine. There will be no blood collection exclusively for the study.

Eligibility criteria: Inclusion Criteria:

* preterm infants of less than 37 weeks of gestational age who have undergone mechanical ventilation within the first 72 hours of life

Exclusion Criteria:

* Major congenital malformations or chromosomal syndromes Mothers carrying the HIV virus.

Primary outcomes:
measure: bronchopulmonary dysplasia
timeFrame: 28 days
Secondary outcomes:
measure: TNF
timeFrame: 5 days
measure: IL-10
timeFrame: 5 days
measure: IL-6
timeFrame: 5 days
measure: IL-8
timeFrame: 5 days
measure: IL1b
timeFrame: 5 days
measure: IL2
timeFrame: 5days
Other outcomes:
Locations:
Study officials:
affiliation: Federal University of Rio Grande do Sul
name: Rita de Cassia Silveira
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nunes CR, Procianoy RS, Corso AL, Silveira RC. Use of Azithromycin for the Prevention of Lung Injury in Mechanically Ventilated Preterm Neonates: A Randomized Controlled Trial. Neonatology. 2020;117(4):522-528. doi: 10.1159/000509462. Epub 2020 Sep 7.