Vitamin C, Hydrocortisone and Thiamine in Patients With Septic Shock

NCT05192213 | Terminated Phase 3 DMC

• 2 other identifiers: AVAP-NG 100007445119.9.1001.5461
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 12

Brief Summary

A great interest exists regarding substances with an immunomodulatory effect for sepsis patients. Recent data have shown that intravenous vitamin C, together with corticosteroids and thiamine, could prevent progressive organ dysfunction and reduce vasopressor use in patients with severe sepsis and septic shock. Its effect on mortality, on the other hand, is yet to be demonstrated. The Vitamins study aims to conclusively determine, through its prospective, multicentre and double-blinded design including 1090 patients, wether Vitamin C, Thiamine and Hydrocortisone in combination can reduce mortality in patients with septic shock.

Conditions

Sepsis; Septic Shock

Keywords

sepsis; septic shock; vitamin C; thiamine; ICU

Outcome Measures

Primary Outcomes (1)

• 28-day Mortality

  Mortality by all causes at 28 days after randomization

  28 days

Secondary Outcomes (4)

• 90-day Mortality

  90 days

• Duration of support

  28 days

• Delta SOFA

  72 hours

• Quality of life assessment

  6 months

Other Outcomes (3)

• Duration of hospital stay

  Until hospital discharge or up to 90 days of randomisation

• Changes in Inflammatory Markers

  Up to 96 hours of randomisation

• Incidence of Treatment-Emergent Adverse Events

  28 days

Study Arms (2)

Intervention

EXPERIMENTAL

1,5 g of vitamin C every 6 hours + 200 mg of thiamine every 12 hours + 50 mg of hydrocortisone every 6 hours For 7 days or until patient's discharge/death

Drug: Vitamin C

Control

PLACEBO COMPARATOR

Placebo 1 for vitamin C every 6 hours + Placebo 2 for thiamine every 12 hours + 50 mg of hydrocortisone every 6 hours For 7 days or until patient's discharge/death

Other: Placebo

Interventions

Vitamin C DRUG

Patients will be allocated in a 1: 1 ratio to the treatment group, receiving intravenous Vitamin C (1.5 g every 6 hours), Thiamine (200 mg every 12 hours) and Hydrocortisone (50 mg every 6 hours) for 7 days

Also known as: thiamine, hydrocortisone

Intervention

Placebo OTHER

Patients will receive 2 placebos (every 6 hours and every 12 hours) + Hydrocortisone (50 mg every 6 hours) for 7 days.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Above 18 years of age
• Sepsis of any background
• Vasopressor-dependent sepsis for at least 2 hours and vasopressor dose ≥ 0.25 µg / kg / min

You may not qualify if:

• Pregnancy;
• Requests for DNR (do not resuscitate) / DNI (do not intubate);
• Death is considered imminent or inevitable during this hospitalization and the attending physician, patient or substitute decision maker is not committed to active treatment;
• Patients with acute cerebral vascular event, acute coronary syndrome, active gastrointestinal bleeding, burn or trauma at admission;
• Patients with known HIV infection;
• Patients with known glucose-6 phosphate dehydrogenase (G-6PD) deficiency;
• Patients with septic shock transferred from another ICU or hospital with characteristics of septic shock for\> 12 hours;
• Patients with septic shock characteristics for\> 12 hours;
• Patients with a known history of oxalate nephropathy;
• Patients with short bowel syndrome or severe known fat malabsorption;
• Patients with acute beriberi disease;
• Patients with acute Wernicke's encephalopathy;
• Patients with known malaria;
• Patients with known or suspected scurvy;
• Patients with known or suspected Addison's disease;

Sponsors & Collaborators

• Hospital Sirio-Libanes: lead
• PROADI-SUS: collaborator
• Ministry of Health, Brazil: collaborator

Study Sites (12)

Hospital Maternidade São Vicente de Paulo

Barbalha, Ceará, Brazil

Location

Hospital Otoclinica

Fortaleza, Ceará, 60135-100, Brazil

Location

Hospital Evangélico de Vila Velha

Vila Velha, Espírito Santo, Brazil

Location

Hospital Clínica São Roque

Ipiaú, Estado de Bahia, Brazil

Location

Hospital Felício Rocho

Belo Horizonte, Minas Gerais, Brazil

Location

Santa Casa de Misericordia de Passos

Passos, Minas Gerais, 37904-020, Brazil

Location

Hospital Universitário de Maringá

Maringá, Paraná, 87083-240, Brazil

Location

Hospital de Amor - Unidade Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

Hospital SEPACO

São Paulo, São Paulo, 04102-900, Brazil

Location

Hospital Naval Marcílio Dias

Rio de Janeiro, Brazil

Location

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP

São Paulo, Brazil

Location

Hospital São Paulo

São Paulo, Brazil

Location

Related Publications (14)

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  PMID: 28098591 BACKGROUND

• 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.

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• Fujita I, Hirano J, Itoh N, Nakanishi T, Tanaka K. Dexamethasone induces sodium-dependant vitamin C transporter in a mouse osteoblastic cell line MC3T3-E1. Br J Nutr. 2001 Aug;86(2):145-9. doi: 10.1079/bjn2001406.

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• Marik PE. Critical illness-related corticosteroid insufficiency. Chest. 2009 Jan;135(1):181-193. doi: 10.1378/chest.08-1149.

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• he10 leading causes of death by country income group 2012. WHO factsheets. [http://www.who.int/mediacentre/factsheets/fs310/en/index1.html ]

  BACKGROUND

• Sales Junior JA, David CM, Hatum R, Souza PC, Japiassu A, Pinheiro CT, Friedman G, Silva OB, Dias MD, Koterba E, Dias FS, Piras C, Luiz RR; Grupo de Estudo de Sepse do Fundo AMIB. [An epidemiological study of sepsis in Intensive Care Units: Sepsis Brazil study]. Rev Bras Ter Intensiva. 2006 Mar;18(1):9-17. Portuguese.

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• 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.

  PMID: 27162802 BACKGROUND

• Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y. Corticosteroids for treating sepsis. Cochrane Database Syst Rev. 2015 Dec 3;2015(12):CD002243. doi: 10.1002/14651858.CD002243.pub3.

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• Fujii T, Luethi N, Young PJ, Frei DR, Eastwood GM, French CJ, Deane AM, Shehabi Y, Hajjar LA, Oliveira G, Udy AA, Orford N, Edney SJ, Hunt AL, Judd HL, Bitker L, Cioccari L, Naorungroj T, Yanase F, Bates S, McGain F, Hudson EP, Al-Bassam W, Dwivedi DB, Peppin C, McCracken P, Orosz J, Bailey M, Bellomo R; VITAMINS Trial Investigators. 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. JAMA. 2020 Feb 4;323(5):423-431. doi: 10.1001/jama.2019.22176.

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• Hager DN, Hooper MH, Bernard GR, Busse LW, Ely EW, Fowler AA, Gaieski DF, Hall A, Hinson JS, Jackson JC, Kelen GD, Levine M, Lindsell CJ, Malone RE, McGlothlin A, Rothman RE, Viele K, Wright DW, Sevransky JE, Martin GS. The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) Protocol: a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial. Trials. 2019 Apr 5;20(1):197. doi: 10.1186/s13063-019-3254-2.

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MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Ascorbic Acid; Thiamine; Hydrocortisone

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Luciano CP Azevedo, PhD

  Hospital Sirio-Libanês

  PRINCIPAL INVESTIGATOR

• Gisele Queiroz, MD

  Hospitla Sirio-Libanês

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2021
• First Posted: January 14, 2022
• Study Start: August 1, 2021
• Primary Completion: July 14, 2022
• Study Completion: September 19, 2022
• Last Updated: January 30, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (12)