Cited by 253Sepsis Diagnosis and TreatmentVitamin C and Antioxidants ResearchAdrenal Hormones and Disorders

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

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Moskowitz, Ari, Huang, David T., Hou, Peter C., Gong, Jonathan, Doshi, Pratik B., Grossestreuer, Anne V., Andersen, Lars W., Ngo, Long, Sherwin, Robert L., Berg, Katherine M., Chase, Maureen, Cocchi, Michael N., McCannon, Jessica B., Hershey, Mark, Hilewitz, Ayelet, Korotun, Maksim, Becker, Lance B, Otero, Ronny M, Uduman, Junior, Sen, Ayan, Donnino, Michael W., for the ACTS Clinical Trial Investigators·2020·JAMA

DOI 10.1001/jama.2020.11946PMC PMC7435341

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Abstract

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.

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Authors: Moskowitz, A., Huang, D. T., Hou, P. C., Gong, J., Doshi, P. B., Grossestreuer, A. V., Andersen, L. W., Ngo, L., Sherwin, R. L., Berg, K. M., Chase, M., Cocchi, M. N., McCannon, J. B., Hershey, M., Hilewitz, A., Korotun, M., Becker, L. B., Otero, R. M., Uduman, J., Sen, A., Donnino, M. W., & for the ACTS Clinical Trial Investigators
Affiliations: Beth Israel Deaconess Medical Center (US)
University of Pittsburgh (US)
Brigham and Women's Hospital (US)
Hofstra University (US)
The University of Texas Health Science Center at Houston (US)
Wayne State University (US)
Mount Auburn Hospital (US)
South Shore Hospital (US)
Oakland University (US)
Henry Ford Health (US)
Mayo Clinic (US)
Corresponding author: Donnino, Michael W.
ORCID: Moskowitz, Ari
Huang, David T.
Hou, Peter C.
Gong, Jonathan
Doshi, Pratik B.
Grossestreuer, Anne V.
Andersen, Lars W.
Ngo, Long
Berg, Katherine M.
Chase, Maureen
Cocchi, Michael N.
Hilewitz, Ayelet
Korotun, Maksim
Becker, Lance B
Uduman, Junior
Sen, Ayan
Donnino, Michael W.
Venue: JAMA
Publisher: American Medical Association (AMA)
Published: 2020-08-18
Volume: 324
Issue: 7
Pages: 642
ISSN: 0002-9955 (ISSN-L)
0098-7484
DOI: 10.1001/jama.2020.11946
PMC: PMC7435341
OpenAlex: W3069087306
Semantic Scholar: a9205794d79affdd861a6a28192f566070b621c8
Cited by: 253
References: 25
Citations by year: 2026: 19 · 2025: 29 · 2024: 25 · 2023: 37 · 2022: 57 · 2021: 75 · 2020: 11
FWCI: 32.23
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: JAMA (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Massachusetts General Hospital
University of Pittsburgh
Open Philanthropy Project
National Institutes of Health
National Institute of General Medical Sciences (K23GM128005)
Topics: Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords: septic shock, vitamin C, cortisol, thiamine, organ failure, SOFA score, renal failure, 30-day mortality, combination therapy, sepsis
MeSH terms: Adrenal Cortex Hormones, Adult, Aged, Ascorbic Acid, Cross Infection, Drug Therapy, Combination, Female, Humans, Hyperglycemia, Hypernatremia, Male, Middle Aged, Multiple Organ Failure, Shock, Septic, Thiamine, Proportional Hazards Models, Treatment Failure, Organ Dysfunction Scores

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

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