Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/22439
Title: Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial.
Authors: Fujii, Tomoko;Luethi, Nora;Young, Paul J;Frei, Daniel R;Eastwood, Glenn M;French, Craig J;Deane, Adam M;Shehabi, Yahya;Hajjar, Ludhmila A;Oliveira, Gisele;Udy, Andrew A;Orford, Neil;Edney, Samantha J;Hunt, Anna L;Judd, Harriet L;Bitker, Laurent;Cioccari, Luca;Naorungroj, Thummaporn;Yanase, Fumitaka;Bates, Samantha;McGain, Forbes;Hudson, Elizabeth P;Al-Bassam, Wisam;Dwivedi, Dhiraj Bhatia;Peppin, Chloe;McCracken, Phoebe;Orosz, Judit;Bailey, Michael;Bellomo, Rinaldo
Affiliation: Clinical School of Medicine, University of New South Wales, Sydney, Australia
Department of Intensive Care, Anaesthesia, Pain, and Perioperative Medicine, Footscray Hospital, Western Health, Footscray, Melbourne, Victoria, Australia
Service de médecine intensive et réanimation, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
Intensive Care Unit, Wellington Hospital, Capital and Coast District Health Board, Wellington, New Zealand
Medical Research Institute of New Zealand, Wellington, New Zealand
Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine, Kyoto, Japan
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Australia
Intensive Care Unit, Austin Health, Heidelberg, Victoria, Australia
Department of Intensive Care and Hyperbaric Medicine, Alfred Hospital, Melbourne, Victoria, Australia
Intensive Care Unit, University Hospital Geelong, Barwon Health, Geelong, Victoria, Australia
School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia
University of Melbourne, Parkville, Victoria, Australia
Department of Intensive Care, Siriraj Hospital, Mahidol University, Bangkok, Thailand
Department of Intensive Care Medicine, University Hospital, University of Bern, Bern, Switzerland
Critical Care and Perioperative Services, School of Clinical Sciences, Monash University and Monash Health, Melbourne, Victoria, Australia
Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia
Department of Anaesthesia and Pain Medicine, Wellington Hospital, Capital and Coast District Health Board, Wellington, New Zealand
Cancer Institute of the State of Sao Paulo, Sao Paulo, Brazil
Intensive Care Unit, Wellington Hospital, Capital and Coast District Health Board, Wellington, New Zealand
Issue Date: 17-Jan-2020
EDate: 2020-01-17
Citation: JAMA 2020; online first: 17 January
Abstract: It is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock. To determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock. Multicenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019. Patients were randomized to the intervention group (n = 109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n = 107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days. The primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were prespecified, including 90-day mortality. Among 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], 76.3-145.4 hours) in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was -0.6 hours (95% CI, -8.3 to 7.2 hours; P = .83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported. In patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. The finding suggests that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone. ClinicalTrials.gov Identifier: NCT03333278.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22439
DOI: 10.1001/jama.2019.22176
ORCID: 0000-0002-1650-8939
0000-0003-4993-427X
0000-0002-1650-8939
PubMed URL: 31950979
Type: Journal Article
Appears in Collections:Journal articles

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