Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
116 participants
INTERVENTIONAL
2018-12-01
2020-04-14
Brief Summary
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Detailed Description
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Vitamin C plays a role in mediating inflammation through antioxidant activities and is also important as a cofactor/co-substrate for the synthesis of endogenous adrenaline, cortisol, and vasopressin. Recently, several clinical trials have reported the positive effects of vitamin C on outcomes in sepsis or septic shock. During sepsis, vitamin C prevents neutrophil-induced lipid oxidation and protects against the loss of the endothelial barrier. Early intravenous supplementation is therefore needed to limit loss of microcirculation and oxidation of lipids. Thiamine is also a key cofactor for glucose metabolism, the generation of ATP (adenosine triphosphate), and the production of NADPH. Considering acute consumption in the hypermetabolic state, thiamine supplementation might be a reasonable therapeutic adjunct for patients with sepsis and was added to reduce the risk of renal oxalate crystallization. These findings led to a recent before-and-after study showing that treatment of sepsis with a combination of vitamin C, hydrocortisone, and thiamine prevented organ dysfunction and reduced the mortality rate.
The aim of this study is to evaluate the efficacy of early metabolic resuscitation with combination therapy using vitamin C and thiamine in improving organ function and survival in patients with septic shock.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Treatment
Combination therapy of vitamin C and thiamine for 2 days.
Combination therapy of vitamin C and thiamine
Vitamin C (50 mg/kg up to 3 g, every 12 hours) and thiamine (200 mg every 12 hours) intravenously administered mixed in 50 mL solution bags of normal saline for 2 days
Control
Normal Saline Solution
Normal saline solution
Normal saline solution in a volume to match the treatment components administered mixed in 50 mL solution bags of normal saline for 2 days
Interventions
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Combination therapy of vitamin C and thiamine
Vitamin C (50 mg/kg up to 3 g, every 12 hours) and thiamine (200 mg every 12 hours) intravenously administered mixed in 50 mL solution bags of normal saline for 2 days
Normal saline solution
Normal saline solution in a volume to match the treatment components administered mixed in 50 mL solution bags of normal saline for 2 days
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Septic shock: sepsis with persisting hypotension requiring vasopressors to maintain a mean arterial pressure ≥65 mm Hg and a serum lactate level \>2 mmol/L despite adequate volume resuscitation. Sepsis is defined as clinically suspected or confirmed infection with acute organ failure identified as an acute change in total SOFA score with 2 points or more.
15. Inability or refusal of a subject or legal surrogate to give informed consent
Exclusion Criteria
2. Patients who signed a "Do not attempt resuscitation" order or who had set limitations on invasive care
3. Patients who have a terminal, unresponsive illness and survival discharge is not expected (metastatic terminal cancer, etc.)
4. Patients who experienced cardiac arrest before enrollment or when death is anticipated within 24 hours despite maximal treatment
5. Patients who take more than 1g of Vitamin C per day before enrollment or who take supplemental thiamine
6. Pregnant woman
7. Known Glucose-6-phosphate dehydrogenase deficiency
8. Patients with a history of hypersensitivity to vitamin C or thiamine
9. Known Mediterranean anemia
10. Known hyperoxaluria
11. Known cystinuria
12. Acute gout attack
13. Known oxalate renal stone
19 Years
89 Years
ALL
No
Sponsors
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National Research Foundation of Korea
OTHER
Tae Gun Shin
OTHER
Responsible Party
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Tae Gun Shin
Associate professor
Principal Investigators
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Tae Gun Shin, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Samsung Medical Center, Sungkyunkwan University School of Medicine
Locations
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Department of Emergency Medicine, Seoul National University Bundang Hospital,
Seongnam-si, Gyeonggi-do, South Korea
Department of Emergency Medicine, Borame Medical Center, Seoul National University, College of Medicine
Seoul, , South Korea
Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine,
Seoul, , South Korea
Department of Emergency Medicine, Seoul National University College of Medicine,
Seoul, , South Korea
Department of Emergency Medicine, University of Ulsan College of Medicine, Asan Medical Center,
Seoul, , South Korea
Department of Emergency Medicine, Yonsei University College of Medicine
Seoul, , South Korea
Countries
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References
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Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
Hwang SY, Park JE, Jo IJ, Kim S, Chung SP, Kong T, Shin J, Lee HJ, You KM, Jo YH, Kim D, Suh GJ, Kim T, Kim WY, Kim YJ, Ryoo SM, Choi SH, Shin TG; Korean Shock Society (KoSS) Investigators. Combination therapy of vitamin C and thiamine for septic shock in a multicentre, double-blind, randomized, controlled study (ATESS): study protocol for a randomized controlled trial. Trials. 2019 Jul 11;20(1):420. doi: 10.1186/s13063-019-3542-x.
Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017 Mar;45(3):486-552. doi: 10.1097/CCM.0000000000002255.
Teng J, Pourmand A, Mazer-Amirshahi M. Vitamin C: The next step in sepsis management? J Crit Care. 2018 Feb;43:230-234. doi: 10.1016/j.jcrc.2017.09.031. Epub 2017 Sep 18.
Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest. 2017 Jun;151(6):1229-1238. doi: 10.1016/j.chest.2016.11.036. Epub 2016 Dec 6.
Oudemans-van Straaten HM, Spoelstra-de Man AM, de Waard MC. Vitamin C revisited. Crit Care. 2014 Aug 6;18(4):460. doi: 10.1186/s13054-014-0460-x.
Donnino MW, Andersen LW, Chase M, Berg KM, Tidswell M, Giberson T, Wolfe R, Moskowitz A, Smithline H, Ngo L, Cocchi MN; Center for Resuscitation Science Research Group. Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study. Crit Care Med. 2016 Feb;44(2):360-7. doi: 10.1097/CCM.0000000000001572.
Zabet MH, Mohammadi M, Ramezani M, Khalili H. Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock. J Res Pharm Pract. 2016 Apr-Jun;5(2):94-100. doi: 10.4103/2279-042X.179569.
Fowler AA 3rd, Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, Farthing CA, Larus TL, Martin E, Brophy DF, Gupta S; Medical Respiratory Intensive Care Unit Nursing; Fisher BJ, Natarajan R. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014 Jan 31;12:32. doi: 10.1186/1479-5876-12-32.
May JM, Harrison FE. Role of vitamin C in the function of the vascular endothelium. Antioxid Redox Signal. 2013 Dec 10;19(17):2068-83. doi: 10.1089/ars.2013.5205. Epub 2013 May 29.
Leite HP, de Lima LF. Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic? J Thorac Dis. 2016 Jul;8(7):E552-7. doi: 10.21037/jtd.2016.05.37.
de Grooth HJ, Geenen IL, Girbes AR, Vincent JL, Parienti JJ, Oudemans-van Straaten HM. SOFA and mortality endpoints in randomized controlled trials: a systematic review and meta-regression analysis. Crit Care. 2017 Feb 24;21(1):38. doi: 10.1186/s13054-017-1609-1.
Park JE, Jo YH, Hwang SY, Kim WY, Ryoo SM, Jang DH, Kim T, Kim YJ, Kim S, Cho H, Lee GT, Chung SP, Choi SH, Shin TG, Suh GJ; Korean Shock Society (KoSS) Investigators. Biomarker Analysis for Combination Therapy of Vitamin C and Thiamine in Septic Shock: A Post-Hoc Study of the ATESS Trial. Shock. 2022 Jan 1;57(1):81-87. doi: 10.1097/SHK.0000000000001850.
Other Identifiers
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2018R1C1B6006821
Identifier Type: -
Identifier Source: org_study_id