Comparison of Standard Versus Double Dose of Amoxicillin in the Treatment of Non-Severe Pneumonia in Children Aged 2-59 Months: A Multi-centre Randomized Double Blind Controlled Trial in Pakistan
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 900
- 试验地点
- 2
- 主要终点
- Number of children with non-severe pneumonia failing treatment with standard and double dose amoxicillin
研究概览
简要总结
Over a period of years there have been numerous reports from many developing countries including Pakistan showing a rising treatment failure rate with first line drugs (amoxicillin and cotrimoxazole) in non-severe pneumonia in children. The reasons for this rise in treatment failure rates are not entirely clear but one of the reasons is thought to be increasing antimicrobial resistance of H. influenzae and Strep. pneumoniae to first line drugs. There is microbiological data which suggests that this resistance can be overcome by increasing the dose of amoxicillin. The investigators propose to treat non-severe pneumonia with double dose amoxicillin in an attempt to demonstrate a decrease in treatment failure rates. This will be a multicentre, double blind randomized controlled trial in children 2-59 months of age with non-severe pneumonia comparing the clinical outcome between the standard and double dose groups.
It has been felt that the WHO criteria for treatment failure in children with pneumonia are too stringent and have never been systematically evaluated in the community. The investigators also propose to modify WHO criteria and field test them in this trial in an attempt to demonstrate that less stringent treatment failure criteria would have an impact on the overall treatment failure rates in pneumonia.
Hypothesis:
Therapy outcome with double dose of oral amoxicillin is not different than the standard dose of amoxicillin, when used for three days for the treatment of non-severe pneumonia in 2-59 months old children.
详细描述
INTRODUCTION:
World Health Organization's (WHO) standard case management strategy for reducing ARI related mortality recommends oral cotrimoxazole and oral amoxicillin as first line drugs for the treatment of pneumonia. In 1989, the Pakistan Ministry of Health (MOH) adopted this strategy to control ARI mortality and recommended cotrimoxazole for treatment of outpatients pneumonia due to lower costs. A number of studies subsequently performed have shown significant in vivo and in vitro resistance of H. influenzae and S. pneumoniae, the commonest bacteria causing childhood pneumonia, to cotrimoxazole.
This increase in clinical failure with oral cotrimoxazole has put a lot of pressure both at national and international forums on the National ARI Control Programme of Pakistan to change its recommendations from cotrimoxazole to amoxicillin as the first line of therapy. Besides being efficacious for non-severe pneumonia amoxicillin has shown good efficacy in children with severe pneumonia and bacteremic children.
although on a case by case basis for pneumonia, in vitro resistance does not correlate very well with in vivo failures. One can hypothesize that if bacterial pneumonia is a certain proportion of all pneumonia cases, the rise in clinical failures may be related to increasing antimicrobial resistance of S. pneumoniae and H. influenzae to amoxicillin.
It is felt that WHO criteria for treatment failure are too stringent. Improvement is defined as the return of respiratory rate to below the cut off for that particular age at 48 hours. Some of the children with viral pneumonia will continue to have respiratory rate above the cut off on the first follow-up. These children are otherwise well and show no signs of deterioration of the disease but according to WHO criteria they would be classified as treatment failure. The treatment failure rates hence are influenced by the definitions used.
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
- Double
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
- •They are aged 2-59 months.
- •Diagnosed with WHO defined non-severe pneumonia (Table 1).
排除标准
- •Children with signs of WHO defined severe or very severe disease.
- •Known penicillin allergy, with a history of accelerated rash, urticaria, or anaphylactic symptoms. Complicating acute non-pulmonary or chronic illness .
- •The children living outside the municipal limits of the city who cannot be followed up .
- •Children who have taken the appropriate doses of WHO-recommended dose of anti microbial drug for 48 hours prior to presentation .
- •Children who have prior history of wheezing or bronchial asthma and are wheezing now .
- •Children whose parents or guardians refuse to give consent.
- •Previously enrolled patients in the present study.
- •Hospitalization in the past two weeks.
结局指标
主要结局
Number of children with non-severe pneumonia failing treatment with standard and double dose amoxicillin
次要结局
- To measure the difference in treatment failure rates by day 5 by using the treatment failure definitions by WHO and the modified study definitions.