AZTEC—azithromycin therapy for prevention of chronic lung disease of prematurity: a statistical analysis plan for clinical outcomes
Abstract Background The AZTEC trial is a multi-centre, randomised, placebo-controlled trial of azithromycin to improve survival without development of chronic lung disease of prematurity (CLD) in preterm infants. The statistical analysis plan for the clinical outcomes of the AZTEC trial is described...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-08-01
|
| Series: | Trials |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13063-022-06604-2 |
| _version_ | 1811281888723075072 |
|---|---|
| author | Tin Man Mandy Lau John Lowe Timothy Pickles Kerenza Hood Sailesh Kotecha David Gillespie |
| author_facet | Tin Man Mandy Lau John Lowe Timothy Pickles Kerenza Hood Sailesh Kotecha David Gillespie |
| author_sort | Tin Man Mandy Lau |
| collection | DOAJ |
| description | Abstract Background The AZTEC trial is a multi-centre, randomised, placebo-controlled trial of azithromycin to improve survival without development of chronic lung disease of prematurity (CLD) in preterm infants. The statistical analysis plan for the clinical outcomes of the AZTEC trial is described. Methods and design A double-blind, randomised, placebo-controlled trial of a 10-day course of intravenous azithromycin (20 mg/kg for 3 days; 10 mg/kg for 7 days) administered to preterm infants born at < 30 weeks’ gestational age across UK tertiary neonatal units. Following parental consent, infants are randomly allocated to azithromycin or placebo, with allocated treatment starting within 72 h of birth. The primary outcome is survival without moderate/severe CLD at 36 weeks’ postmenstrual age (PMA). Serial respiratory fluid and stool samples are being collected up to 21 days of life. The target sample size is 796 infants, which is based on detecting a 12% absolute difference in survival without moderate/severe CLD at 36 weeks’ PMA (90% power, two-sided alpha of 0.05) and includes 10% loss to follow-up. Results Baseline demographic and clinical characteristics will be summarised by treatment arm and in total. Categorical data will be summarised by numbers and percentages. Continuous data will be summarised by mean, standard deviation, if data are normal, or median, interquartile range, if data are skewed. Tests of statistical significance will not be undertaken for baseline characteristics. The primary analysis, on the intention to treat (ITT) population, will be analysed using multilevel logistic regression, within a multiple imputation framework. Adjusted odds ratios, 95% confidence intervals, and p-values will be presented. For all other analyses, the analysis population will be based on the complete case population, which is a modified ITT population. All analyses will be adjusted for gestational age and treatment arm and account for any clustering by centre and/or multiple births as a random effect. Conclusion We describe the statistical analysis plan for the AZTEC trial, including the analysis principles, definitions of the key clinical outcomes, methods for primary analysis, pre-specified subgroup analysis, sensitivity analysis, and secondary analysis. The plan has been finalised prior to the completion of recruitment. Trial registration ISRCTN registry ISRCTN11650227. Registered on 31 July 2018. |
| first_indexed | 2024-04-13T01:41:43Z |
| format | Article |
| id | doaj.art-2c705b4e215b4362b12c518ab2697466 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-04-13T01:41:43Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-2c705b4e215b4362b12c518ab26974662022-12-22T03:08:10ZengBMCTrials1745-62152022-08-0123111110.1186/s13063-022-06604-2AZTEC—azithromycin therapy for prevention of chronic lung disease of prematurity: a statistical analysis plan for clinical outcomesTin Man Mandy Lau0John Lowe1Timothy Pickles2Kerenza Hood3Sailesh Kotecha4David Gillespie5Centre for Trials Research, Cardiff UniversityCentre for Trials Research, Cardiff UniversityCentre for Trials Research, Cardiff UniversityCentre for Trials Research, Cardiff UniversityDepartment of Child Health, School of Medicine, Cardiff UniversityCentre for Trials Research, Cardiff UniversityAbstract Background The AZTEC trial is a multi-centre, randomised, placebo-controlled trial of azithromycin to improve survival without development of chronic lung disease of prematurity (CLD) in preterm infants. The statistical analysis plan for the clinical outcomes of the AZTEC trial is described. Methods and design A double-blind, randomised, placebo-controlled trial of a 10-day course of intravenous azithromycin (20 mg/kg for 3 days; 10 mg/kg for 7 days) administered to preterm infants born at < 30 weeks’ gestational age across UK tertiary neonatal units. Following parental consent, infants are randomly allocated to azithromycin or placebo, with allocated treatment starting within 72 h of birth. The primary outcome is survival without moderate/severe CLD at 36 weeks’ postmenstrual age (PMA). Serial respiratory fluid and stool samples are being collected up to 21 days of life. The target sample size is 796 infants, which is based on detecting a 12% absolute difference in survival without moderate/severe CLD at 36 weeks’ PMA (90% power, two-sided alpha of 0.05) and includes 10% loss to follow-up. Results Baseline demographic and clinical characteristics will be summarised by treatment arm and in total. Categorical data will be summarised by numbers and percentages. Continuous data will be summarised by mean, standard deviation, if data are normal, or median, interquartile range, if data are skewed. Tests of statistical significance will not be undertaken for baseline characteristics. The primary analysis, on the intention to treat (ITT) population, will be analysed using multilevel logistic regression, within a multiple imputation framework. Adjusted odds ratios, 95% confidence intervals, and p-values will be presented. For all other analyses, the analysis population will be based on the complete case population, which is a modified ITT population. All analyses will be adjusted for gestational age and treatment arm and account for any clustering by centre and/or multiple births as a random effect. Conclusion We describe the statistical analysis plan for the AZTEC trial, including the analysis principles, definitions of the key clinical outcomes, methods for primary analysis, pre-specified subgroup analysis, sensitivity analysis, and secondary analysis. The plan has been finalised prior to the completion of recruitment. Trial registration ISRCTN registry ISRCTN11650227. Registered on 31 July 2018.https://doi.org/10.1186/s13063-022-06604-2Chronic lung disease of prematurityBronchopulmonary dysplasiaPreterm infantsRandomised controlled trialAzithromycinMacrolide |
| spellingShingle | Tin Man Mandy Lau John Lowe Timothy Pickles Kerenza Hood Sailesh Kotecha David Gillespie AZTEC—azithromycin therapy for prevention of chronic lung disease of prematurity: a statistical analysis plan for clinical outcomes Trials Chronic lung disease of prematurity Bronchopulmonary dysplasia Preterm infants Randomised controlled trial Azithromycin Macrolide |
| title | AZTEC—azithromycin therapy for prevention of chronic lung disease of prematurity: a statistical analysis plan for clinical outcomes |
| title_full | AZTEC—azithromycin therapy for prevention of chronic lung disease of prematurity: a statistical analysis plan for clinical outcomes |
| title_fullStr | AZTEC—azithromycin therapy for prevention of chronic lung disease of prematurity: a statistical analysis plan for clinical outcomes |
| title_full_unstemmed | AZTEC—azithromycin therapy for prevention of chronic lung disease of prematurity: a statistical analysis plan for clinical outcomes |
| title_short | AZTEC—azithromycin therapy for prevention of chronic lung disease of prematurity: a statistical analysis plan for clinical outcomes |
| title_sort | aztec azithromycin therapy for prevention of chronic lung disease of prematurity a statistical analysis plan for clinical outcomes |
| topic | Chronic lung disease of prematurity Bronchopulmonary dysplasia Preterm infants Randomised controlled trial Azithromycin Macrolide |
| url | https://doi.org/10.1186/s13063-022-06604-2 |
| work_keys_str_mv | AT tinmanmandylau aztecazithromycintherapyforpreventionofchroniclungdiseaseofprematurityastatisticalanalysisplanforclinicaloutcomes AT johnlowe aztecazithromycintherapyforpreventionofchroniclungdiseaseofprematurityastatisticalanalysisplanforclinicaloutcomes AT timothypickles aztecazithromycintherapyforpreventionofchroniclungdiseaseofprematurityastatisticalanalysisplanforclinicaloutcomes AT kerenzahood aztecazithromycintherapyforpreventionofchroniclungdiseaseofprematurityastatisticalanalysisplanforclinicaloutcomes AT saileshkotecha aztecazithromycintherapyforpreventionofchroniclungdiseaseofprematurityastatisticalanalysisplanforclinicaloutcomes AT davidgillespie aztecazithromycintherapyforpreventionofchroniclungdiseaseofprematurityastatisticalanalysisplanforclinicaloutcomes |