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Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Ari Moskowitz, Harvard University
  • ,
  • David T. Huang, University of Pittsburgh
  • ,
  • Peter C. Hou, Harvard University
  • ,
  • Jonathan Gong, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
  • ,
  • Pratik B. Doshi, McGovern Medical School
  • ,
  • Anne V. Grossestreuer, Harvard University
  • ,
  • Lars W. Andersen
  • Long Ngo, Harvard University
  • ,
  • Robert L. Sherwin, Wayne State University School of Medicine
  • ,
  • Katherine M. Berg, Harvard University
  • ,
  • Maureen Chase, Harvard University
  • ,
  • Michael N. Cocchi, Harvard University
  • ,
  • Jessica B. McCannon, Mount Auburn Hospital
  • ,
  • Mark Hershey, South Shore Hospital
  • ,
  • Ayelet Hilewitz, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
  • ,
  • Maksim Korotun, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
  • ,
  • Lance B. Becker, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
  • ,
  • Ronny M. Otero, Oakland University William Beaumont School of Medicine
  • ,
  • Junior Uduman, Henry Ford Hospital, Detroit, Michigan.
  • ,
  • Ayan Sen, Mayo Clinic Scottsdale-Phoenix, Arizona
  • ,
  • Michael W. Donnino, Harvard University
  • ,
  • ACTS Clinical Trial Investigators

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.

Original languageEnglish
JournalJAMA
Volume324
Issue7
Pages (from-to)642-650
Number of pages9
ISSN0098-7484
DOIs
Publication statusPublished - Aug 2020

    Research areas

  • ADULTS, DOUBLE-BLIND, HYDROCORTISONE, SEPSIS, VITAMIN-C

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