Supportive care and antibiotics for severe pneumonia among hospitalized children: A pragmatic randomised controlled trial

住院儿童重症肺炎的支持治疗和抗生素：一项实用的随机对照试验

• 批准号: MR/R006083/1
• 负责人: Ambrose Agweyu
• 金额: $ 307.72万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR006083%2F1
• 关键词: Supportive; care; antibiotics; severe; pneumonia

Pneumonia, an infection of the lungs, is the leading cause of deaths among young children. The World Health Organization (WHO) have developed recommendations for the diagnosis and treatment of pneumonia in low and middle income countries using simple clinical features and low cost, widely available antibiotics. The recommend treatment for children at the highest risk of death (severe pneumonia) is injectable benzylpenicillin or ampicillin and gentamicin. Following the introduction of vaccines against the main causes of pneumonia to national immunization programmes in many low-income countries, there has been growing debate over the appropriateness of the currently recommended treatments. Many clinicians already believe that the recommended treatment is ineffective and frequently opt to use other antibiotics such as amoxicillin-clavulanic acid and ceftriaxone instead. The first key question in this study seeks to compare two antibiotics against the current recommended treatment. We will investigate is whether either (i) intravenous amoxicillin-clavulanic acid or (ii) ceftriaxone is superior to benzylpenicillin plus gentamicin (standard care) for the treatment of children admitted to hospital with severe pneumonia. Some authorities advise against feeding through a tube inserted into the stomach through the nose in severely ill children. The main reason for this is are the potential for compromising the ability to breath in a patient already experiencing difficulty breathing and an increased risk of choking on feeds given through the tube. However, the alternative, providing fluids through an intravenous drip requires careful monitoring by a nurse to ensure the fluid is given at a safe rate over the desired duration. This a common challenge in many low resource settings where a limited number of nursing staff are required to attend to several duties. Fluids provided through a drip are also lack the necessary nutrients to match the increased demands of the body during a serious illness. The second key question for this study is therefore whether feeding through a tube inserted into the stomach through the nose is superior to providing fluids through an intravenous drip for the management of children with severe pneumonia.We will recruit 4392 children at 12 hospitals in Kenya. Children who meet the criteria for recruitment will be allocated to the study treatment groups through a balanced process pre-determined process that ensures each participant has a fair chance of receiving any given study treatments. Each of the two questions will be studied in the same set of patients. Thus, a child recruited in the study will receive any one of the three antibiotic treatments and either of the two fluid treatments. For each of the study questions, we will compare the percentage of children who die within the first five day of recruitment in the alternative treatment groups. We will also compare the length of hospitalisation, and the percentage of children who die within 30 days of recruitment in the alternative treatment groups. Chest X-rays and blood samples will be collected in a smaller group of patients to examine possible explanations for differences in responses to the treatments. Finally, we will compare the costs of receiving the alternative study treatments against the outcomes we observe among children assigned to the respective study groups and explore the social perceptions of caregivers and health workers towards the treatments.

肺炎是一种肺部感染，是幼儿死亡的主要原因。世界卫生组织（世卫组织）已经制定了在低收入和中等收入国家使用简单的临床特征和低成本、广泛可用的抗生素诊断和治疗肺炎的建议。对于死亡风险最高的儿童（严重肺炎），推荐的治疗方法是注射用苄青霉素或氨苄青霉素和庆大霉素。在许多低收入国家的国家免疫方案中引入针对肺炎主要病因的疫苗后，对目前建议的治疗方法是否适当的争论越来越多。许多临床医生已经认为推荐的治疗无效，并经常选择使用其他抗生素，如阿莫西林-克拉维酸和头孢曲松。本研究的第一个关键问题是将两种抗生素与目前推荐的治疗方法进行比较。我们将研究（i）静脉注射阿莫西林-克拉维酸或（ii）头孢曲松是否上级苄青霉素加庆大霉素（标准治疗）治疗因重症肺炎入院的儿童。一些权威人士建议，对重病儿童，不要通过鼻子插入胃中的管子进食。其主要原因是可能损害已经经历呼吸困难的患者的呼吸能力，并且增加了通过管给予的饲料窒息的风险。然而，通过静脉滴注提供液体的替代方案需要护士仔细监测，以确保在所需的持续时间内以安全的速率提供液体。这是许多低资源环境中的一个共同挑战，在这些环境中，需要有限数量的护理人员来履行几项职责。通过点滴提供的液体也缺乏必要的营养，以满足严重疾病期间身体增加的需求。因此，本研究的第二个关键问题是，对于患有严重肺炎的儿童的管理，通过鼻子插入胃中的管子进食是否上级通过静脉滴注提供液体。我们将在12家医院招募4392名儿童肯尼亚。符合招募标准的儿童将通过平衡的预先确定的过程分配至研究治疗组，以确保每名受试者有公平的机会接受任何给定的研究治疗。这两个问题中的每一个都将在同一组患者中进行研究。因此，研究中招募的儿童将接受三种抗生素治疗中的任何一种和两种液体治疗中的任何一种。对于每个研究问题，我们将比较替代治疗组中招募后前5天内死亡的儿童百分比。我们还将比较住院时间的长短，以及在替代治疗组招募后30天内死亡的儿童百分比。将在一个较小的患者组中收集胸部X线和血液样本，以检查对治疗反应差异的可能解释。最后，我们将比较接受替代研究治疗的成本与我们在分配到相应研究组的儿童中观察到的结果，并探讨护理人员和卫生工作者对治疗的社会认知。

项目成果

Malaria hospitalisation in East Africa: age, phenotype and transmission intensity.

• DOI: 10.1186/s12916-021-02224-w
• 发表时间: 2022-01-27
• 期刊: BMC medicine
• 影响因子: 9.3
• 作者: Kamau A;Paton RS;Akech S;Mpimbaza A;Khazenzi C;Ogero M;Mumo E;Alegana VA;Agweyu A;Mturi N;Mohammed S;Bigogo G;Audi A;Kapisi J;Sserwanga A;Namuganga JF;Kariuki S;Otieno NA;Nyawanda BO;Olotu A;Salim N;Athuman T;Abdulla S;Mohamed AF;Mtove G;Reyburn H;Gupta S;Lourenço J;Bejon P;Snow RW
• 通讯作者: Snow RW

Employing learning health system principles to advance research on severe neonatal and paediatric illness in Kenya.

• DOI: 10.1136/bmjgh-2021-005300
• 发表时间: 2021-03
• 期刊: BMJ global health
• 影响因子: 8.1
• 作者: English M;Irimu G;Akech S;Aluvaala J;Ogero M;Isaaka L;Malla L;Tuti T;Gathara D;Oliwa J;Agweyu A
• 通讯作者: Agweyu A

Additional file 2 of Malaria hospitalisation in East Africa: age, phenotype and transmission intensity

东非疟疾住院的附加文件 2：年龄、表型和传播强度

• DOI: 10.6084/m9.figshare.19076361
• 发表时间: 2022
• 作者: Kamau A

Additional file 1 of Malaria hospitalisation in East Africa: age, phenotype and transmission intensity

东非疟疾住院的附加文件 1：年龄、表型和传播强度

• DOI: 10.6084/m9.figshare.19076355
• 发表时间: 2022
• 作者: Kamau A

Additional file 3 of Malaria hospitalisation in East Africa: age, phenotype and transmission intensity

东非疟疾住院的附加文件 3：年龄、表型和传播强度

• DOI: 10.6084/m9.figshare.19076364
• 发表时间: 2022
• 作者: Kamau A