Azithromycin Therapy for Chronic Lung Disease of Prematurity
Research type
Research Study
Full title
A randomised, placebo controlled trial of azithromycin for the prevention of chronic lung disease of prematurity in preterm infants
IRAS ID
108978
Contact name
Chris Shaw
Contact email
Sponsor organisation
Cardiff University
Eudract number
2018-001109-99
Duration of Study in the UK
3 years, 4 months, 31 days
Research summary
Summary of Research
Premature births account for a tenth of all world-wide births. Babies who survive are at risk of developing Chronic Lung Disease of Prematurity (CLD) as they have underdeveloped lungs, and also because the necessary treatment (breathing machines and oxygen therapy) in itself causes harm. CLD is defined as needing oxygen at 36 weeks “corrected” gestation. Most babies will come off their oxygen therapy by the end of their hospital stay, however, some babies go home on oxygen placing enormous burden on families. CLD babies also have a higher risk of childhood breathing problems. Inflammation (like redness or soreness) of the lungs is often seen in CLD babies, and a germ called Ureaplasma is often present. Some doctors’ think that Ureaplasma is a simple 'bystander', but others believe that it is actively causing harm- we have shown that babies who have Ureaplasma have much greater chances of developing CLD than those who do not. Researchers have previously used antibiotics, such as azithromycin, to treat the Ureaplasma. Azithromycin decreases lung inflammation and is an effective antibiotic against Ureaplasma. A recent report combining 3 studies noted that rates of CLD may improve with azithromycin therapy but the total number of babies included were small. A large study is needed to see if azithromycin therapy can indeed improve CLD rate. We, therefore, will investigate if ten days of intravenous azithromycin improves survival without CLD in premature babies. We shall collect lung fluid samples via their breathing tube or from their nose/back of the mouth, and nappy stool samples. These will be used to see if lung Ureaplasma is successfully treated by azithromycin, and if common germs found in the gut and lungs develop antibiotic resistance. Studying resistance is important as azithromycin will be widely used if we show that the therapy improves rates of CLD.Summary of Results
Why did we do this study?
Many premature babies will develop a disease called Chronic Lung Disease of Prematurity (CLD) during their stay in hospital. CLD develops due to the impact of additional oxygen and breathing support given to help the babies' lungs, which are too immature to work independently. Our previous research has shown that infection and inflammation (redness and soreness) are increased in babies who develop CLD. CLD can lead to more hospital admissions in infancy, and breathing problems during childhood and beyond. Azithromycin is an antibiotic which has been shown to treat both lung infections (particularly a bacteria called Ureaplasma) and inflammation and might reduce the number of babies who develop CLD. So, we planned the AZTEC trial to assess if 10 days of azithromycin treatment improved rates of survival without CLD in prematurely born babies when compared to a placebo (dummy) medicine.What did we do?
Between October 2019 and March 2022, we enrolled 799 babies in the trial. Approximately half received azithromycin, and half received placebo. We assessed how many babies developed CLD in each group. We also took respiratory samples to look for infections (particularly Ureaplasma) and stool samples to look at whether giving azithromycin increased resistance to antibiotics.What did we find?
We found that treatment with azithromycin, although apparently safe, did not change rates of CLD compared to the placebo medicine. Our findings mean that we cannot recommend its use in premature babies to improve breathing outcomes. Also, we found that carriage of antibiotic resistant genes in poo and lung secretions in babies increased over babies' stay in hospital when they received azithromycin.What does this mean for premature babies with CLD?
The results mean that premature babies should not routinely be given azithromycin early after birth as an additional medicine to help with their breathing. Since premature babies may need many medicines for their care, this message is important. Researchers will need to look at other options for improving outcomes for breathing problems, which might include combinations of medicines or other therapies.REC name
Wales REC 2
REC reference
18/WA/0199
Date of REC Opinion
26 Jun 2018
REC opinion
Further Information Favourable Opinion