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Protocol
Study protocol: azithromycin therapy for chronic lung disease of prematurity (AZTEC) - a randomised, placebo-controlled trial of azithromycin for the prevention of chronic lung disease of prematurity in preterm infants
  1. John Lowe1,
  2. David Gillespie1,
  3. Marie Hubbard2,
  4. Lei Zhang3,
  5. Nigel Kirby1,
  6. Timothy Pickles1,
  7. Emma Thomas-Jones1,
  8. Mark A Turner4,
  9. Nigel Klein5,
  10. Julian R Marchesi6,
  11. Kerenza Hood1,
  12. Janet Berrington7,
  13. Sailesh Kotecha3
  1. 1Centre for Trials Research, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
  2. 2Neonatal Intensive Care Unit, University Hospitals of Leicester NHS Trust, Leicester, Leicester, UK
  3. 3Department of Child Health, School of Medicine, Cardiff University, Cardiff, United Kingdom
  4. 4Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
  5. 5GOS Institute of Child Health, University College London, London, London, UK
  6. 6School of Biosciences, Cardiff University, Cardiff, UK
  7. 7Neonatal Intensive Care Unit, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
  1. Correspondence to Professor Sailesh Kotecha; KotechaS{at}cardiff.ac.uk

Abstract

Introduction Chronic lung disease of prematurity (CLD), also known as bronchopulmonary dysplasia (BPD), is a cause of significant respiratory morbidity in childhood and beyond. Coupled with lung immaturity, infections (especially by Ureaplasma spp) are implicated in the pathogenesis of CLD through promotion of pulmonary inflammation. Azithromycin, which is a highly effective against Ureaplasma spp also has potent anti-inflammatory properties. Thus, azithromycin therapy may improve respiratory outcomes by targeting infective and inflammatory pathways. Previous trials using macrolides have not been sufficiently powered to definitively assess CLD rates. To address this, the azithromycin therapy for chronic lung disease of prematurity (AZTEC) trial aims to determine if a 10-day early course of intravenous azithromycin improves rates of survival without CLD when compared with placebo with an appropriately powered study.

Methods and analysis 796 infants born at less than 30 weeks’ gestational age who require at least 2 hours of continuous respiratory support within the first 72 hours following birth are being enrolled by neonatal units in the UK. They are being randomised to receive a double-blind, once daily dose of intravenous azithromycin (20 mg/kg for 3 days, followed by 10 mg/kg for a further 7 days), or placebo. CLD is being assessed at 36 weeks’ PMA. Whether colonisation with Ureaplasma spp prior to randomisation modifies the treatment effect of azithromycin compared with placebo will also be investigated. Secondary outcomes include necrotising enterocolitis, intraventricular/cerebral haemorrhage, retinopathy of prematurity and nosocomial infections, development of antibiotic resistance and adverse reactions will be monitored.

Ethics and dissemination Ethics permission has been granted by Wales Research Ethics Committee 2 (Ref 18/WA/0199), and regulatory permission by the Medicines and Healthcare Products Regulatory Agency (Clinical Trials Authorisation reference 21323/0050/001–0001). The study is registered on ISRCTN (ISRCTN11650227). The study is overseen by an independent Data Monitoring Committee and an independent Trial Steering Committee. We shall disseminate our findings via national and international peer-reviewed journals, and conferences. A summary of the findings will also be posted on the trial website.

  • neonatology
  • paediatric thoracic medicine
  • chronic airways disease
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This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

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Footnotes

  • Contributors SK is the Chief Investigator who developed the research question and secured funding together with JL, MT and JB, with subsequent input from JRM, NK, KH, DG and ETJ. JL and SK wrote the protocol with input from all authors. JL is the Trial Manager, managed by ETJ, Senior Trial Manager, and is responsible for coordinating the operational delivery of the protocol and recruitment. DG and TP are the Trial Statisticians and authored the statistical analysis plan. JL and NKi led the development of the case report forms; NKi supervises data management. LZ is the Laboratory Analyst; expert microbiology advice is provided by NK and JRM. SK, MT, MH and JB provide expert clinical input; MH provides nursing and clinical expertise. JL wrote the first draft of the manuscript supervised by SK. All authors provided critical review and final approval of the manuscript.

  • Funding This work is supported by the National Institute of Health Research Health Technology Assessment programme (Ref 16/111/106). The study duration is 01 January 2019 to 30 September 2022.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer-reviewed.

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