Division of Pulmonary & Critical Care Medicine, Department of Medicine, Johns Hopkins Hospital, Johns Hopkins University, 1800 Orleans Street, Suite 9121, Baltimore, MD, 21287, USA.
Division of Pulmonary & Critical Care Medicine, Department of Medicine, Eastern Virginia Medical School and Sentara Healthcare, Norfolk, VA, USA.
Trials. 2019 Apr 5;20(1):197. doi: 10.1186/s13063-019-3254-2.
Sepsis accounts for 30% to 50% of all in-hospital deaths in the United States. Other than antibiotics and source control, management strategies are largely supportive with fluid resuscitation and respiratory, renal, and circulatory support. Intravenous vitamin C in conjunction with thiamine and hydrocortisone has recently been suggested to improve outcomes in patients with sepsis in a single-center before-and-after study. However, before this therapeutic strategy is adopted, a rigorous assessment of its efficacy is needed.
The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled trial. It will enroll patients with sepsis causing respiratory or circulatory compromise or both. Patients will be randomly assigned (1:1) to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 h or matching placebos until a total of 16 administrations have been completed or intensive care unit discharge occurs (whichever is first). Patients randomly assigned to the comparator group are permitted to receive open-label stress-dose steroids at the discretion of the treating clinical team. The primary outcome is consecutive days free of ventilator and vasopressor support (VVFDs) in the 30 days following randomization. The key secondary outcome is mortality at 30 days. Sample size will be determined adaptively by using interim analyses with pre-stated stopping rules to allow the early recognition of a large mortality benefit if one exists and to refocus on the more sensitive outcome of VVFDs if an early large mortality benefit is not observed.
VICTAS is a large, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled trial that will test the efficacy of vitamin C, thiamine, and hydrocortisone as a combined therapy in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. Because the components of this therapy are inexpensive and readily available and have very favorable risk profiles, demonstrated efficacy would have immediate implications for the management of sepsis worldwide.
ClinicalTrials.gov Identifier: NCT03509350 . First registered on April 26, 2018, and last verified on December 20, 2018. Protocol version: 1.4, January 9, 2019.
在美国，败血症导致的住院患者死亡人数占比为 30%至 50%。除了抗生素和源头控制外，治疗策略主要是支持性的，包括液体复苏以及呼吸、肾脏和循环支持。最近，一项单中心的前后对照研究提示，败血症患者联合应用维生素 C、硫胺素和皮质类固醇可以改善结局。然而，在采用这种治疗策略之前，需要对其疗效进行严格评估。
维生素 C、硫胺素和类固醇治疗败血症（VICTAS）试验是一项前瞻性、多中心、双盲、适应性样本量、随机、安慰剂对照试验。将招募因败血症导致呼吸或循环功能障碍或两者均有的患者。患者将被随机分配（1:1）接受静脉注射维生素 C（1.5 g）、硫胺素（100 mg）和皮质类固醇（50 mg），每 6 小时 1 次，或接受匹配的安慰剂，直至完成 16 次给药或转入重症监护病房（以先发生者为准）。随机分配至对照组的患者可根据治疗临床团队的判断接受开放标签应激剂量类固醇。主要结局为随机分组后 30 天内连续无呼吸机和血管加压药支持天数（VVFDs）。次要结局为 30 天死亡率。样本量将通过使用预先设定的停止规则的中期分析进行适应性确定，以便在存在较大死亡率获益时尽早识别，并在未观察到早期较大死亡率获益时将重点转向更敏感的 VVFDs 结局。
VICTAS 是一项大型、多中心、双盲、适应性样本量、随机、安慰剂对照试验，旨在测试维生素 C、硫胺素和皮质类固醇联合治疗因败血症导致呼吸或循环功能障碍（或两者均有）的患者的疗效。由于该治疗方案的组成部分价格低廉且易于获得，风险状况良好，因此如果证明有效，将立即对全球败血症的治疗产生影响。
ClinicalTrials.gov 标识符：NCT03509350。首次注册于 2018 年 4 月 26 日，最后一次验证于 2018 年 12 月 20 日。方案版本：1.4，2019 年 1 月 9 日。
