Preparation for the Randomised Evaluation of a VItamin C bundle for Sepsis Treatment in Africa (REVISTA-Prep)

要点：1)败血症是一种危及生命的感染，可导致重要器官衰竭；它每年造成700多万人死亡，其中很大一部分发生在非洲。2)新出现的研究表明，使用氢化可的松（类固醇）、静脉注射维生素C（抗坏血酸）和静脉注射维生素B1（硫胺素）联合进行“代谢复苏”治疗败血症患者有希望获得好处。3)美国、欧洲、亚洲和南美正在进行不同的研究，以了解这些药物的组合或单独使用是否有助于提高脓毒症患者的几率。虽然这些研究都没有在非洲进行，但这种治疗方法中所包含的不同药物价格低廉，容易获得，而且使用起来相对安全。4)至关重要的是，在非洲进行类似的研究，以评估提供这些药物中的任何一种或它们的组合是否有助于挽救那里的人免于死于败血症。5)如果研究证明这些药物可以提高败血症患者的存活率，那么就有很大的可能挽救许多人的生命，因为每一种药物都很便宜，容易获得，而且相对安全。通过这个联合全球健康试验发展奖，我们打算在乌干达（东非）进行初步研究，以帮助我们更好地了解我们可能需要考虑什么来进行未来的大型试验，研究维生素C、维生素B1和类固醇（或单独药物）的哪种组合最能提高非洲环境中败血症的存活率，在那里资源有限，重症监护病房很少，贫困等问题，营养不良和艾滋病毒很常见。具体来说，我们将进行一系列小型研究，以了解感染艾滋病毒的败血症患者与感染或未感染艾滋病毒的健康人相比，维生素C和B1缺乏症的常见程度。我们还将调查是否这些维生素水平低与败血症患者死亡之间存在联系。此外，我们将为另一小群败血症患者提供不同剂量的维生素C（以及维生素B1），这样我们就可以更好地了解在未来的试验中应该使用的正确剂量，以及是否有任何实验室测试或临床症状我们可以用来专门监测维生素C水平。最后，由于我们将在一群重病患者中进行未来的试验，我们希望采访临床医生、患者和生活在社区中的人们，了解他们对参加一项大型临床试验的理解，在这项试验中，尚不清楚所研究的药物是否能帮助您，以及您将无法决定最终将随机接受哪种不同药物。我们将使用从该开发奖励中收集的所有信息来申请全额奖励，以便为更大规模的试验获得资金。

Preparation for Randomised Evaluation of a VItamin C bundle for Sepsis Treatment in Africa (REVISTA-Prep)Key points:1) Sepsis is a life-threatening infection that can result in failure of vital organs; it is responsible for more than 7 million deaths annually, a large percentage of which occur in Africa. 2) Emerging research shows promising benefits in patients with sepsis treated with "metabolic resuscitation" using combinations of hydrocortisone (steroids), intravenous vitamin C (ascorbic acid) and intravenous vitamin B1 (thiamine). 3) Different studies are underway in the US, Europe, Asia, and South America to understand whether combinations of these medicines or the medicines individually can help improve the chances of someone with sepsis. Although none of these studies are being conducted in Africa, the different medicines that are included in this treatment are inexpensive, readily available and relatively safe to administer. 4) It is critical that similar studies are conducted in Africa to evaluate whether or not providing any of these medicine or a combination of them can help save people there from dying of sepsis.5) If the studies prove that these medicines can improve survival from sepsis, there is a large potential to save many lives because each of the medicines are inexpensive, readily available and relatively safe to administer. Through this Joint Global Health Trials Development Award, we intend to conduct preliminary research in Uganda (East Africa) to help us understand better what we might need to consider for conducting a future large trial that studies which of the combinations of vitamin C, vitamin B1, and steroids (or the medicines individually) will be best at improving survival from sepsis in African settings, where the resources are constrained, intensive care units are rare, and issues like poverty, malnutrition, and HIV are common. Specifically, we will conduct a series of small studies to understand how common deficiencies of vitamin C and B1 are in sepsis patients who are HIV-infected compared to healthy individuals with and without HIV. We will also investigate or not there is a link between having low levels of these vitamins and death in sepsis patients. In addition, we will provide varying doses of vitamin C (alongside vitamin B1) to another small group of sepsis patients so we can gain a better understanding of the correct dose we should use in the future trial and whether there are any laboratory tests or clinical signs we can use to monitor the vitamin C levels specifically. Finally, because we will be conducting the future trial in a population of patients who are severely ill, we would like to interview clinicians, patients, and people living in the community about their understanding of what it means to be enrolled in a large clinical trial for which it is unclear whether the medicine being studied can help you and where you will not be able to decide which of the different medicines you will ultimately be randomised to receive. We will use all the information we collect from this development award to apply for a full award in order to get funding for the larger trial.