Amoxicillin Versus Benzyl Penicillin for Severe Childhood Pneumonia Amongst Inpatients: An Open Label Randomised Controlled Non-inferiority Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 561
- 试验地点
- 6
- 主要终点
- Treatment Failure at 48 Hours (Two Full Days After Enrollment)
研究概览
简要总结
This study seeks to determine whether clinical outcome following initial treatment of severe pneumonia with oral amoxicillin is as effective as the current standard benzyl penicillin. The study will also provide an estimate of the proportion of Kenyan children with severe pneumonia who fail treatment with a single antibiotic.
详细描述
Case management for the treatment of childhood acute respiratory infections has been widely promoted in many developing countries for over 20 years. Despite this, pneumonia continues to claim over 1.5 million lives of children under five annually. The use of affordable, easily-administered, safe, effective treatments can potentially reduce the burden of childhood pneumonia. The WHO recommends the use of a single antibiotic for the treatment of severe pneumonia. Whereas in Asia, evidence from large randomized clinical trials has changed policy recommendations for treatment of severe pneumonia from parenteral penicillin to oral amoxicillin, there is little evidence to inform a similar move in African children where pneumonia is associated with poorer outcomes. In this study the investigators will investigate effectiveness of oral amoxicillin versus the current standard treatment, benzyl penicillin in severe childhood pneumonia using a randomized controlled non-inferiority design preceded by a pilot pre-intervention phase. The investigators will also collect observational data HIV-exposed / infected children with severe pneumonia. 594 children aged 2 - 59 months admitted with clinical signs of severe pneumonia to up to 7 hospitals in Kenya will be randomly assigned to receive either oral amoxicillin or injectable benzyl penicillin. They will then be followed up for the primary outcome of pre-defined treatment failure at 48 hours. The results of this trial will provide valuable data on the effectiveness of oral amoxicillin in the treatment of severe pneumonia in a population of Kenyan children and determine the practicability of conducting large pragmatic trials on pneumonia in Africa similar to those done in Asia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Months 至 59 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical signs of WHO-defined severe pneumonia
- •Age 2 months to 59 months
排除标准
- •Clinical signs of WHO-defined very severe pneumonia
- •Clinical or laboratory diagnosis of meningitis
- •Clinical diagnosis of severe malnutrition (marasmus/kwashiorkor)
- •Clinical or laboratory diagnosis of severe anaemia requiring transfusion
- •HIV-exposure on rapid HIV antibody test (only observational data will be collected from these patients)
- •Elimination of signs of severe pneumonia in a child with wheeze after outpatient bronchodilator therapy
- •Chronic condition that may underlie or contribute to a presentation with respiratory distress such as: known chronic renal or cardiac disease, presence of cerebral palsy predisposing child to aspiration/hypostatic pneumonia
- •Established bronchiectasis or congenital abnormality of the lower respiratory tract
- •Upper airway obstruction producing stridor
- •Admission from outpatient clinic specifically for treatment of TB
- •Referral from another inpatient facility following treatment with injectable antibiotics for more than 24 hours or because the initial regimen is considered to have failed
- •Documented history of >48hours treatment with oral amoxicillin
- •Failure to obtain informed consent
- •Penicillin allergy
研究组 & 干预措施
Amoxicillin 45mg/kg 12 hourly
干预措施: Amoxicillin (Drug)
Benzyl Penicillin 50,000IU/kg 6 hourly
干预措施: Benzyl penicillin (Drug)
结局指标
主要结局
Treatment Failure at 48 Hours (Two Full Days After Enrollment)
时间窗: 48 hours
Development of any signs of very severe pneumonia at any time Hypoxemia defined as SpO2 \<85% or \<80% for altitude \< or ≥1500m respectively measured after minimum of 3 minutes on ambient air Persistent vomiting (occurring within 30 minutes of administration of amoxicillin with failure to retain drug after 3 successive attempts at administration) at any time Clinical diagnosis of new bacterial co-morbid condition requiring revision of antibiotic treatment at any time Lower chest wall indrawing Temperature ≥38◦C Respiratory rate ≥5bpm of admission rate if above age-adjusted normal upper limit
次要结局
- Treatment Failure at or Before Discharge / Day 5 Post Enrollment (Whichever Occurs First)(Patients will be followed up from the day of hospitalisation (day 0) until the day of medical discharge (average duration of 3 days) or until day 5 of hospitalisation (whichever occurs first).)
- Readmission With Diagnosis of Severe or Very Severe Pneumonia Within 14 Days of Enrollment(Day 0 to Day 14)
- Death at or Before Five Days Following Enrollment(Day 0 to Day 5)
- Outcome (Death/Readmission) at 14 Days as Determined by Telephone or Direct Interview(Day 14)