A Randomised, Placebo Controlled Trial of Azithromycin for the Prevention of Chronic Lung Disease of Prematurity in Preterm Infants
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 试验地点
- 16
- 主要终点
- The proportion of surviving infants without CLD (Chronic Lung Disease) in the azithromycin treatment group when compared to placebo at 36 weeks post-menstrual age.
研究概览
简要总结
The aim of the TINN2 study is to evaluate the efficacy of azithromycin in prevention of bronchopulmonary dysplasia in preterm neonates.
详细描述
In contrast to the situation in adults, most medicines used to treat the children of Europe have not been tested and are not authorised for use in children. In particular, 46% medicines prescribed to children in hospital are either unlicensed for their age group or, if licensed, are prescribed off label. Of the children who receive at least one medication in hospital, 67% receive an unlicensed or off-label drug, and in the context of intensive care, this rises to up to 90% of patients.
The new Paediatric Regulation entered into force in early 2007 ensure that medicines for use in children are of high quality, ethically evaluated and authorised appropriately. The Paediatric-Use Marketing Authorisation (PUMA) is a new type of marketing authorisation for drugs not covered by a patent, already available on the market for adults. PUMA applies to medicines lacking information and/or appropriate formulation for children of all ages.
Thus, the European Medicines Agency (EMA) has published a list of drugs, which azithromycin belongs, as priority medicinal products needing an evaluation in the paediatric population.
Bronchopulmonary dysplasia (BPD) is a specific disease of prematurity accompanied by pulmonary inflammation. Multiple factors may contribute to the occurrence of BPD. In infants who are at risk of developing CLD, one frequent finding is colonisation of the preterm lung with the microbe Ureaplasma.
Two Meta-Analyses and recent studies have suggested an association between the presence of pulmonary Ureaplasma and the development of BPD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 23 Weeks 至 28 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pre-term, 28w + 6d gestational age (i.e. 28 weeks and 6 days, including infants born as one of a multiple birth)
- •Requirement for respiratory support within 12hrs of birth (intubated, or by noninvasive mechanical ventilation including continuous positive airway pressure)
- •Presence of an indwelling intravenous line for drug administration
- •Inborn, or born at site within the recruiting centre's neonatal network where follow up will be possible
排除标准
- •In the opinion of the PI, babies unlikely to survive until 48 hours after birth
- •Exposure to another macrolide antibiotic
- •Presence of major surgical or congenital abnormalities (not including patent ductus arteriosus or patent foramen ovale)
- •Infants born as part of a multiple pregnancy of three or more (i.e. triplets or more)
- •Contraindication of azithromycin as specified in the summary of characteristics of the product.
- •Participation in other clinical trials involving Investigational Medicinal Products (IMPs)
研究组 & 干预措施
Azithromycin
10mg/kg azithromycin IV daily (administered over a period of at least one 1 hour) for a period of 10 days.
干预措施: Azithromycin (Drug)
Placebo
Placebo IV daily (administered over a period of at least one 1 hour) for a period of 10 days.
干预措施: Placebo (Drug)
结局指标
主要结局
The proportion of surviving infants without CLD (Chronic Lung Disease) in the azithromycin treatment group when compared to placebo at 36 weeks post-menstrual age.
时间窗: 36 weeks post-menstrual age
次要结局
- Number of Adverse Events(24 months)
- C-Reactive Protein(24 months)
- Severity of CLD (Chronic Lung Disease) according to NIH definition(36 weeks PMA)
- Duration of positive pressure respiratory support (i.e. conventional mechanical ventilation, nasal ventilation, continuous positive airway pressure, CPAP) and supplemental oxygen(up to 36 weeks PMA)
- Mortality rate (at 28 days, 36 weeks PMA, 2 years)(28 days, 36 weeks PMA, 2 years)
- Microbiology assessment(Baseline and days 5, 10, 21)
- Inflammation Markers(Baseline and days 5, 10, 21)
- Emergence of resistance to azithromycin in Ureaplasma spp. isolated from endotracheal or nasopharyngeal samples at baseline, days 5, 10 and 21(Baseline, days 5, 10 and 21)
- Resistance to azithromycin among microbes isolated from stool or rectal swab obtained at baseline and day 21(Baseline and day 21)
- Plasma concentrations(days 1, 3, 6 as required)
- Exposure to antibiotics other than azithromycin during the hospital stay(up to 36weeks PMA)
- Development of complications of prematurity(24 months)
- Number of participants with dysrhythmic episodes and QTc interval(24 months)
- Neurodevelopmental assessment: Assessment of neurodevelopment using the 3rd edition of the Bayley Scales of Infant Development at the corrected age of 24 months(24 months)
- Respiratory function assessment: Assessment of respiratory symptoms using a validated International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire(24 months)