Interrupted lung development
Very preterm birth occurs during rapid growth of the airways, air sacs and pulmonary blood vessels.
The AZTEC Trial
Why was AZTEC needed?
Babies born very preterm are at increased risk of chronic lung disease because their lungs are still developing and can be exposed to inflammation, respiratory support and infection during a critical period of lung growth.
AZTEC was designed to test whether azithromycin could target both inflammation and organisms such as Ureaplasma, and thereby improve important lung outcomes.
The clinical problem
Chronic lung disease of prematurity
Chronic lung disease of prematurity, often termed bronchopulmonary dysplasia (BPD), remains one of the most important complications of very preterm birth. Some affected babies need oxygen or respiratory support for prolonged periods and respiratory problems can persist after discharge.
Inflammation
Inflammatory pathways are implicated in lung injury and impaired lung development.
Microbiology
Ureaplasma and other organisms may influence inflammatory responses and risk of chronic lung disease.
Trial design
How did AZTEC work?
AZTEC was a multicentre, randomised, double-blind, placebo-controlled trial. Babies were allocated to azithromycin or placebo, with treatment started early after birth and given for 10 days.
Who could take part?
Infants born before 30 weeks’ gestation receiving neonatal intensive care were considered against the trial eligibility criteria.
What was compared?
Intravenous azithromycin was compared with a matched placebo so families and clinical/research teams remained blinded to treatment allocation.
What was measured?
The primary outcome was survival without physiologically defined moderate or severe chronic lung disease at 36 weeks’ postmenstrual age.
Biological samples
Understanding mechanisms as well as clinical outcomes
AZTEC incorporated microbiological and laboratory studies alongside the clinical trial. Respiratory and stool samples enabled investigators to examine Ureaplasma, inflammatory pathways, the microbiome and antimicrobial resistance.
Respiratory samples
Where possible, small airway samples were obtained during routine neonatal care and used to study organisms and inflammatory mediators.
Stool samples
Gut microbiology and macrolide resistance were investigated, providing important information on antimicrobial-resistance consequences of neonatal antibiotic exposure.
Scale & collaboration
A UK-wide neonatal research partnership
799 babies were recruited across 28 neonatal intensive care units. The trial was led from Cardiff University and coordinated by the Centre for Trials Research, with collaborators from neonatal centres and universities across the UK.
Chief Investigator
Professor Sailesh Kotecha
Department of Child Health, Cardiff University
Trial coordination
Centre for Trials Research
Cardiff University
Collaborators
Co-applicants and investigators included teams from Newcastle, Leicester, Liverpool, UCL, Imperial College London and participating neonatal units throughout the UK.
Funding & governance
How was the study supported?
AZTEC was funded by the NIHR Health Technology Assessment Programme (HTA Project 16/111/106) and registered as ISRCTN11650227.
The trial received the relevant UK research ethics, Health Research Authority and medicines-regulatory approvals.