Trial II of Lung Protection With Azithromycin in the Preterm Infant

The hypothesis of this study is that administration of azithromycin to ventilated premature infants will decrease the incidence and severity of BPD. The purpose of this study is to determine if Azithromycin treatment is beneficial for prevention of bronchopulmonary dysplasia in preterm infants.

The survival of preterm infants has increased dramatically and has been associated with an increase in BPD. The incidence of BPD among extremely low birthweight infants ranges from 45% to 90%. Development of BPD is associated with both antenatal (maternal chorioamnionitis often due to Ureaplasma is related to BPD) and postnatal complications (oxygen toxicity, barotrauma, late onset infections). These insults appear to lead to an inflammatory response with resultant arrest of normal alveolar and vascular development. Multiple human studies support the role of inflammation in the development of BPD. Evaluating a medication that could decrease the inflammation in BPD, with minimal side effects, could significantly improve the morbidities of prematurity and the financial burden incurred by parents. Macrolide antibiotics (erythromycin and azithromycin) have been shown to have anti-inflammatory properties that are independent of their antimicrobial properties. Azithromycin has the potential to decrease the severity of ventilator-induced pulmonary inflammation that is commonly seen in BPD.

vehicle dose given daily, IV/PO, same volume that Azithromycin would be to equal 10 mg/kg for first 7 days, then 5 mg/kg for 5 weeks.

comparison of the % Incidence of bronchopulmonary dysplasia (BPD) for the azithromycin vs placebo groups.

Steroids will be provided as needed based on Standard of Care. Data are presented as the percent of participants that received steroids between birth and discharge from the NICU.

Participants will be placed on mechanical ventilation as necessary based on standard of care. Data are presented as the percent of participants in each group receiving mechanical ventilation.

Data will be collected on the number of participants that did not survive to discharge from the NICU. Data are presented as the percent of participants that did not survive.

Inclusion Criteria: birthweight less than 1250 grams admitted to UK NICU mechanical ventilation within the first 72 hours of life Exclusion Criteria: confirmed sepsis by blood culture multiple congenital anomalies or known syndromes intrauterine growth retardation with birthweight less than 10%ile for gestational age ROM for >7 days

Ballard HO, Shook LA, Bernard P, Anstead MI, Kuhn R, Whitehead V, Grider D, Crawford TN, Hayes D Jr. Use of azithromycin for the prevention of bronchopulmonary dysplasia in preterm infants: a randomized, double-blind, placebo controlled trial. Pediatr Pulmonol. 2011 Feb;46(2):111-8. doi: 10.1002/ppul.21352. Epub 2010 Oct 20.