MICA: Hydroxyurea - Pragmatic Reduction In Mortality and Economic burden (H-PRIME)

MICA：羟基脲 - 务实降低死亡率和经济负担 (H-PRIME)

• 批准号: MR/S004904/1
• 负责人: Thomas Williams
• 金额: $ 570.73万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS004904%2F1
• 关键词: MICA; Hydroxyurea; Pragmatic; Reduction; Mortality

Sickle cell anaemia (SCA) is a common inherited condition that affects around 1% of all children born in much of sub-Saharan Africa. Without early diagnosis and appropriate treatment under-5 mortality in those affected is between 50 and 90%. As a result, through much of the continent SCA is responsible for between 5 and 16% of total under-5 mortality. These high levels of mortality could be reduced dramatically with simple treatments that include educating parents to recognise danger signs and seek emergency care, and by measures that protect against acute bacterial and malarial infections using vaccines and prophylactic antibiotic and anti-malarial drugs. Nevertheless, without specific treatments that modify the course of the disease, many of those affected will live lives that are characterized by frequent and recurrent bouts of severe illness that include acute and chronic pain and progressive multi-organ deterioration. Unlike diseases like HIV, malaria and tuberculosis, SCA does not enjoy a high profile in the eyes of the international community and remains widely neglected by ministries of health through much of sub-Saharan Africa. Through H-PRIME, we will address three key questions in the management of children with SCA in Africa today through a single large, efficient and pragmatic clinical trial. First, we will determine whether hydroxyurea, a common and effective treatment for SCA in resource-rich regions, could be a useful option in parts of Africa with limited access to medical care. In most countries hydroxyurea is administered and monitored in a way that will not be achievable in most of Africa and our primary question, therefore, will be whether the drug can be used safely and effectively to reduce mortality and improve the quality of life in survivors when administered pragmatically following a weight-band-based dosing strategy with minimal clinical and laboratory monitoring. Second, we will investigate whether better protection from bacterial infections in children with SCA can reduce all cause hospital admission and further reduce mortality. The current approach to the prevention of bacterial infections is through the use of oral penicillin. However, this is only effective against a narrow range of bacterial organisms and we will therefore investigate whether the addition of a second agent, co-trimoxazole, could bring further benefits in the absence of harm. Finally, the current approach to the prevention of malaria infections relies on drugs that are associated with high levels of resistance. We will therefore investigate whether malaria prevention with a more modern and highly effective drug - dihidroartemisinin-piperaquine - could be used as an alternative, and that this will not cause harm in terms of side effects and the development of further drug resistance.

镰状细胞性贫血 (SCA) 是一种常见的遗传性疾病，影响撒哈拉以南非洲大部分地区出生的大约 1% 的儿童。如果没有早期诊断和适当的治疗，受影响的 5 岁以下儿童死亡率为 50% 至 90%。因此，在非洲大陆的大部分地区，SCA 占 5 岁以下儿童死亡率的 5% 至 16%。通过简单的治疗，包括教育父母识别危险迹象并寻求紧急护理，以及使用疫苗和预防性抗生素和抗疟疾药物来预防急性细菌和疟疾感染，可以显着降低如此高的死亡率。然而，如果没有改变病程的具体治疗方法，许多受影响的人将过着频繁和反复发作的严重疾病的生活，包括急性和慢性疼痛以及进行性多器官恶化。与艾滋病毒、疟疾和结核病等疾病不同，SCA 在国际社会眼中并不引人注目，并且仍然被撒哈拉以南非洲大部分地区的卫生部广泛忽视。通过 H-PRIME，我们将通过一项大型、高效、务实的临床试验来解决当今非洲 SCA 儿童管理中的三个关键问题。首先，我们将确定羟基脲（一种资源丰富地区常见且有效的 SCA 治疗方法）是否可以成为医疗服务有限的非洲部分地区的有用选择。在大多数国家，羟基脲的管理和监测方式在非洲大部分地区是无法实现的，因此，我们的首要问题是，在以下情况下，是否可以安全有效地使用该药物来降低幸存者的死亡率并改善幸存者的生活质量：按照基于体重带的剂量策略进行务实给药，并进行最少的临床和实验室监测。其次，我们将研究更好地保护 SCA 儿童免受细菌感染是否可以减少全因住院并进一步降低死亡率。目前预防细菌感染的方法是使用口服青霉素。然而，这仅对一小部分细菌有效，因此我们将研究添加第二种药物复方新诺明是否可以在没有危害的情况下带来更多好处。最后，目前预防疟疾感染的方法依赖于具有高耐药性的药物。因此，我们将研究是否可以使用更现代、更高效的药物——双氢青蒿素哌喹——作为预防疟疾的替代方案，并且这不会造成副作用和进一步耐药性的发展。

项目成果

Characterising demographics, knowledge, practices and clinical care among patients attending sickle cell disease clinics in Eastern Uganda.

描述乌干达东部镰状细胞病诊所患者的人口统计、知识、实践和临床护理特征。

• DOI: 10.12688/wellcomeopenres.15847.2
• 发表时间: 2020
• 期刊: Wellcome open research
• 作者: Olupot-Olupot P

Red Blood Cell Deformability Demonstrated with the Oxygenscan: Exploring the Association with Hydroxyurea Treatment, Co-Inherited a-Thalassemia, and Frequency of Pain in Children with Sickle Cell Anemia

使用 Oxygenscan 证明红细胞变形能力：探索与羟基脲治疗、共同遗传性 α-地中海贫血以及镰状细胞性贫血儿童疼痛频率的关系

• DOI: 10.1182/blood-2019-129836
• 发表时间: 2019
• 期刊: Blood
• 影响因子: 20.3
• 作者: Nardo-Marino A

Filling the data gaps on sickle cell anaemia in sub-Saharan Africa.

• DOI: 10.1016/s2352-3026(22)00042-4
• 发表时间: 2022-03
• 期刊: The Lancet. Haematology
• 作者: Williams TN