Importance The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock. Objective To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock. Design, Setting, and Participants Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019. Interventions Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102). Main Outcomes and Measures The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses. Results Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively). Conclusions and Relevance In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock. Trial Registration ClinicalTrials.gov Identifier: NCT03389555.

中文翻译：

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抗坏血酸、皮质类固醇和硫胺素对感染性休克器官损伤的影响

重要性 抗坏血酸、皮质类固醇和硫胺素的组合已被确定为感染性休克的潜在疗法。目的确定抗坏血酸、皮质类固醇和硫胺素的组合是否能减轻感染性休克患者的器官损伤。设计、设置和参与者针对感染性休克成人患者的抗坏血酸、皮质类固醇和硫胺素与安慰剂的随机、双盲、多中心临床试验。2018 年 2 月 9 日至 2019 年 10 月 27 日期间，在美国的 14 个中心招募了 205 名患者。随访持续至 2019 年 11 月 26 日。干预措施患者被随机分配接受肠外抗坏血酸（1500 mg）、氢化可的松（50 mg）、和硫胺素（100 毫克）每 6 小时一次，持续 4 天（n = 103）或安慰剂在相同时间点匹配体积（n = 102）。主要结果和测量 主要结果是入组和 72 小时之间序贯器官衰竭评估 (SOFA) 评分（范围，0-24；0 = 最佳）的变化。关键的次要结局包括肾衰竭和 30 天死亡率。接受至少 1 剂研究药物的患者被纳入分析。结果 在 205 名随机患者（平均年龄 68 [SD，15] 岁；90 [44%] 名女性）中，200 名（98%）至少接受了 1 剂研究药物，完成了试验，并被纳入分析（干预组 101 人，安慰剂组 99 人）。总体，在入组后 72 小时内，时间和治疗组之间在 SOFA 评分方面没有统计学意义的交互作用（干预组的平均 SOFA 评分从 9.1 变为 4.4 [-4.7] 分，而安慰剂组从 9.2 变为 5.1 [-4.1] 分；调整后的平均差，-0.8；95% CI，-1.7 至 0.2；P = .12（交互作用）。肾衰竭的发生率（干预组为 31.7%，安慰剂组为 27.3%；调整后的风险差异为 0.03；95% CI，-0.1 至 0.2；P = 0.58）或 30 天死亡率（分别为 34.7% 和 29.3%；风险比，1.3；95% CI，0.8-2.2；P = .26）。最常见的严重不良事件是高血糖（12 名干预患者和 7 名安慰剂患者）、高钠血症（分别为 11 和 7 名患者）和新的医院获得性感染（13 和 12 名患者，分别）。结论和相关性 在感染性休克患者中，与安慰剂相比，抗坏血酸、皮质类固醇和硫胺素的组合在入组后的前 72 小时内并未导致 SOFA 评分显着降低。这些数据不支持对感染性休克患者常规使用这种联合疗法。试验注册 ClinicalTrials.gov 标识符：NCT03389555。