AZTEC Trial Results

10.05.2024

Summary

Background Systematic reviews have reported conflicting evidence on whether macrolide antibiotics reduce rates of
chronic lung disease of prematurity (CLD) in at-risk preterm infants born at less than 30 weeks’ gestation, including
in those colonised with pulmonary Ureaplasma spp. Since an adequately powered trial has been lacking, we aimed to
assess if the macrolide azithromycin improved survival without the development of physiologically defined moderate
or severe CLD in preterm infants.

Methods

AZTEC was a multicentre, double-blind, randomised, placebo-controlled trial conducted in 28 tertiary
neonatal intensive care units in the UK. Infants were eligible if they were born at less than 30 weeks’ gestation and
had received at least 2 h of either non-invasive (continuous positive airway pressure or humidified high flow nasal
cannula therapy) or invasive respiratory support (via endotracheal tube) within 72 h of birth. Eligible infants were
randomly allocated in a 1:1 ratio using random permuted blocks of four to receive either intravenous azithromycin at
20 mg/kg per day for 3 days followed by 10 mg/kg for 7 days, or to placebo. Allocation was stratified by centre and
gestational age at birth (<28 weeks vs ≥28 weeks). Azithromycin and placebo vials were encased in tamper-evident
custom cardboard cartons to ensure masking for clinicians, parents, and the research team. The primary outcome
was survival without development of physiologically defined moderate or severe CLD at 36 weeks’ postmenstrual age.
Outcomes and safety were analysed on an intention-to-treat basis (all randomly allocated infants, regardless of any
post-randomisation events). The study was registered with ISRCRN (11650227) and is closed.

Findings

Infants were recruited between Oct 9, 2019, and March 22, 2022. 799 (53·1%) of 1505 eligible infants
underwent random allocation; three infants were withdrawn, including consent to use their data, leaving 796 infants
for analysis. Survival without moderate or severe CLD occurred in 166 (42%) of 394 infants in the intervention group
and 179 (45%) of 402 in the placebo group (three-level adjusted OR [aOR] 0·84, 95% CI 0·55–1·29, p=0·43).
Pulmonary Ureaplasma spp colonisation did not influence treatment effect. Overall, seven serious adverse events
were reported for the azithromycin group (five graded as severe, two as moderate), and six serious adverse events
were reported in the placebo group (two severe, two moderate, and two mild), as assessed by the local principal
investigators.

Full article below:

AZTEC LRM 25042024