Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock The ACTS Randomized Clinical Trial
Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock The ACTS Randomized Clinical Trial
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DOI：
10.1001/jama.2020.11946
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发表时间：
2020-08-18
影响因子：
120.7
通讯作者：
Donnino, Michael W.
中科院分区：
文献类型：
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作者：
Moskowitz, Ari;Huang, David T.;Donnino, Michael W.
抗坏血酸、皮质类固醇和硫胺素联合应用已被确定为感染性休克的潜在治疗方法。目的探讨抗坏血酸、糖皮质激素和硫胺素联合应用是否能减轻感染性休克患者的器官损伤。设计、环境和参与者：抗坏血酸、皮质类固醇和硫胺素与安慰剂对感染性休克成年患者的随机、盲法、多中心临床试验。在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225名患者。随访一直持续到2019年11月26日。干预措施患者被随机分配每6小时接受一次静脉注射抗坏血酸（1500 mg）、氢化可的松（50 mg）和硫胺素（100 mg），持续4天（n = 103）或在相同时间点接受相应剂量的安慰剂（n = 102）。主要结局和测量主要结局是入组至72小时间序贯器官衰竭评估（SOFA）评分的变化（范围0-24；0 =最佳）。主要次要结局包括肾衰竭和30天死亡率。接受至少一剂研究药物的患者被纳入分析。结果205例随机患者（平均年龄68 [SD， 15]岁，女性90[44%]）中，200例（98%）接受了至少一剂研究药物，完成了试验，并被纳入分析（干预组101例，安慰剂组99例）。总的来说，时间和治疗组在入组后72小时的SOFA评分方面没有统计学意义上的相互作用（干预组的平均SOFA评分从9.1到4.4[-4.7]分，安慰剂组的平均SOFA评分从9.2到5.1[-4.1]分；调整后的平均差异为-0.8;95% CI, -1.7到0.2；相互作用的P = 0.12）。两组肾衰竭发生率（干预组31.7% vs安慰剂组27.3%；校正风险差为0.03;95% CI, -0.1 ~ 0.2; P = 0.58）和30天死亡率（分别为34.7% vs 29.3%；风险比为1.3;95% CI, 0.8 ~ 2.2; P = 0.26）无统计学差异。最常见的严重不良事件是高血糖（干预组12例，安慰剂组7例）、高钠血症（分别为11例和7例）和新发医院获得性感染（分别为13例和12例）。在脓毒性休克患者中，与安慰剂相比，抗坏血酸、皮质类固醇和硫胺素联合使用在入组后的前72小时内并未导致SOFA评分的统计学显著降低。这些数据不支持对感染性休克患者常规使用这种联合治疗。抗坏血酸、皮质类固醇和硫胺素联合使用对感染性休克中器官损伤的影响是什么？在这项随机临床试验中，包括200名患有感染性休克的成年人，每6小时联合注射抗坏血酸（1500毫克）、氢化可的松（50毫克）和硫胺素（100毫克）治疗4天，干预组在72小时内的顺序器官衰竭评估评分为4.7分，而安慰剂组为4.1分，差异无统计学意义。意义本试验不支持常规使用抗坏血酸、皮质类固醇和硫胺素联合用于感染性休克人群的器官保护。这项随机临床试验比较了氢化可的松、抗坏血酸和硫胺素联合治疗（HAT或Marik方案）与安慰剂对感染性休克患者72小时SOFA评分测量的器官损伤的影响。
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.Question What is the effect of the combination of ascorbic acid, corticosteroids, and thiamine on the trajectory of organ injury in septic shock? Findings In this randomized clinical trial that included 200 adults with septic shock, treatment for 4 days with a combination of parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) vs placebo every 6 hours resulted in a change in the Sequential Organ Failure Assessment score of 4.7 in the intervention group vs 4.1 in the placebo group over 72 hours, a difference that was not statistically significant. Meaning This trial does not support the routine use of the combination of ascorbic acid, corticosteroids, and thiamine for organ protection in septic shock populations.This randomized clinical trial compares the effect of combination hydrocortisone, ascorbic acid, and thiamine (the HAT or Marik protocol) vs placebo on SOFA score-measured organ injury at 72 hours in patients with septic shock.