Vitamin C, Thiamine, and Steroids in Sepsis

NCT03509350 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: IRB00102528IRB00164053
• Study Type: interventional
• Target: 501
• Locations: 1 country
• Sites: 43

Brief Summary

The VItamin C, Thiamine And Steroids in Sepsis (VICTAS) Study is a double-blind, placebo-controlled, adaptive randomized clinical trial designed to investigate the efficacy of the combined use of vitamin C, thiamine and corticosteroids versus indistinguishable placebos for patients with sepsis. The objective of this study is to demonstrate the efficacy of combination therapy using vitamin C, thiamine and corticosteroids in reducing mortality and improving organ function in critically ill patients with sepsis.

Conditions

Sepsis

Keywords

Vitamin C; Thiamine; Corticosteroid

Outcome Measures

Primary Outcomes (1)

• Vasopressor and Ventilator-free Days (VVFD)

  The primary outcome measure is VVFD in the first 30 days after the start of treatment. The endpoint was recorded to the nearest day. Participants who died are scored zero days, even if there was a period during which the participant was alive and free of vasopressors and mechanical ventilation. Participants who must return to ventilation and/or vasopressors had their counters reset at zero days.

  Up to Day 30

Secondary Outcomes (18)

• Mortality at 30 Days

  Day 30

• Intensive Care Unit (ICU) Mortality

  Day 30

• Mortality at 180 Days

  Day 180

• Length of ICU Stay

  Day 30

• Length of Hospital Stay

  Day 30

Study Arms (2)

Treatment Protocol

EXPERIMENTAL

Participants randomized to the treatment protocol will receive the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.

Drug: Vitamin C; Drug: Thiamine; Drug: Hydrocortisone

Control Protocol

PLACEBO COMPARATOR

A placebo to match the VICTAS intervention will be administered for four days or until ICU discharge. During the treatment period, if an indication for steroids exist, the treating physicians are permitted to initiate open-label corticosteroid therapy based on local practice and international guidelines. If this occurs, the hydrocortisone/placebo will be withheld and subjects will be started on open-label corticosteroids.

Drug: Vitamin C Placebo; Drug: Thiamine Placebo; Drug: Hydrocortisone Placebo

Interventions

Vitamin C DRUG

Intravenous vitamin C (1.5 grams every 6 hours) will be administered for 4 days or until ICU discharge.

Also known as: Ascorbic acid

Treatment Protocol

Thiamine DRUG

Intravenous thiamine (100 mg every 6 hours) will be administered for 4 days or until ICU discharge.

Also known as: Thiamine hydrochloride

Treatment Protocol

Hydrocortisone DRUG

Intravenous hydrocortisone (50 mg every 6 hours) will be administered for 4 days or until ICU discharge.

Also known as: Hydrocortisone sodium succinate

Treatment Protocol

Vitamin C Placebo DRUG

A placebo to match intravenous vitamin C (1.5 grams every 6 hours) will be administered for 4 days or until ICU discharge.

Also known as: Placebo

Control Protocol

Thiamine Placebo DRUG

A placebo to match intravenous thiamine (100 mg every 6 hours) will be administered for 4 days or until ICU discharge.

Also known as: Placebo

Control Protocol

Hydrocortisone Placebo DRUG

A placebo to match intravenous hydrocortisone (50 mg every 6 hours) will be administered for 4 days or until ICU discharge. Steroids will be used when clinically indicated.

Also known as: Placebo

Control Protocol

Eligibility Criteria

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

You may qualify if:

• Suspected or confirmed infection as evidenced by ordering of blood cultures and administration of at least one antimicrobial agent
• Anticipated or confirmed intensive care unit (ICU) admission
• Acute respiratory or cardiovascular organ dysfunction attributed to sepsis as evidenced by at least one of the following requirements:
• Vasopressor Requirement - Continuous infusion of norepinephrine, epinephrine, vasopressin, dopamine, phenylephrine or other vasopressor agents at any dose for greater than 1 hour and required to maintain a mean arterial pressure ≥ 65 mm Hg despite intravenous crystalloid infusion of at least 1000cc
• Respiratory Support Requirement - Acute hypoxemic respiratory failure defined as persistent hypoxemia (partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤ 300 or blood oxygen saturation (SpO2)/FiO2 ≤ 315) requiring (1) intubation and mechanical ventilation, or (2) positive pressure ventilation via tight-fitting face mask (i.e. continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) or (3) high flow nasal cannula ≥ 40 liter per minute (LPM) flow and FiO2 ≥ 0.40

You may not qualify if:

• Weight \< 40 kilograms (kg)
• Prior enrollment in this study
• Qualifying organ dysfunction no longer present at the time subject would be randomized
• Cardiovascular or respiratory organ failure caused by an illness other than sepsis
• First episode of qualifying organ dysfunction during the current emergency department (ED) or ICU admission occurred \> 24 hours before the subject could be randomized
• Limitations of care (defined as refusal of cardiovascular and respiratory support modes) including "do not intubate" (DNI) status
• Current hospitalization \> 30 days at time of randomization
• Chronic hypoxemia requiring supplemental non-invasive oxygen (nasal cannula or NIPPV) or home mechanical ventilation
• Chronic cardiovascular failure requiring home mechanical hemodynamic support (e.g., LVAD) or home chemical hemodynamic support (e.g., milrinone)
• Known allergy or contraindication to vitamin C, thiamine, and/or corticosteroids (including previously or currently diagnosed primary hyperoxaluria and/or oxalate nephropathy, or known/suspected ethylene glycol ingestion, or known glucose-6-phosphate dehydrogenase (G6PD) deficiency)
• Use of vitamin C at a dose of \> 1 gram daily within the 24 hours preceding first episode of qualifying organ dysfunction during a given ED or ICU admission
• Chronic disease/illness that, in the opinion of the site investigator, have an expected lifespan of \< 30 days unrelated to current sepsis diagnosis (e.g., stage IV malignancy, neurodegenerative disease, etc.)
• Pregnancy or known active breastfeeding
• Prisoner or Incarceration
• Current participation in another interventional research study

Sponsors & Collaborators

• Emory University: lead
• The Marcus Foundation: collaborator

Study Sites (43)

Maricopa Integrated Health System

Phoenix, Arizona, 80045, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 30322, United States

Location

Stanford University

Stanford, California, 21201, United States

Location

University of Colorado Denver

Denver, Colorado, 19140, United States

Location

Denver Health

Denver, Colorado, 80204, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 94304, United States

Location

Christiana Care

Newark, Delaware, 19718, United States

Location

Medstar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida Jacksonville

Jacksonville, Florida, 32209, United States

Location

Piedmont Healthcare

Atlanta, Georgia, 30078, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

Lousiana State University

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins Bayview

Baltimore, Maryland, 21224, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

University of Maryland School of Medicine

Baltimore, Maryland, 55415, United States

Location

Baystate Health

Springfield, Massachusetts, 01199, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health System

Detroit, Michigan, 27710, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 48202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center Weiler

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center Moses

The Bronx, New York, 10467, United States

Location

Duke University

Durham, North Carolina, 90024, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 43210, United States

Location

University of Cincinnati Physicians Company

Cincinnati, Ohio, 23114, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 45241, United States

Location

Oregon Health Sciences University

Portland, Oregon, 27157, United States

Location

University of Pennsylvania Health System Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 21224, United States

Location

Temple University

Philadelphia, Pennsylvania, 29425, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 19107, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Intermountain Medical Center

Murray, Utah, 84157, United States

Location

University of Utah

Salt Lake City, Utah, 37235, United States

Location

Sentara Healthcare

Norfolk, Virginia, 23507, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

Location

Bon Secours

Richmond, Virginia, 85008, United States

Location

Related Publications (6)

• Williams Roberson S, Nwosu S, Collar EM, Kiehl AL, Harrison FE, Bastarache J, Wilson JE, Mart MF, Sevransky JE, Ely EW, Lindsell CJ, Jackson JC; VICTAS Investigators. Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors: A Secondary Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis Randomized Clinical Trial. JAMA Netw Open. 2023 Feb 1;6(2):e230380. doi: 10.1001/jamanetworkopen.2023.0380.

  PMID: 36853612 DERIVED

• Sevransky JE, Rothman RE, Hager DN, Bernard GR, Brown SM, Buchman TG, Busse LW, Coopersmith CM, DeWilde C, Ely EW, Eyzaguirre LM, Fowler AA, Gaieski DF, Gong MN, Hall A, Hinson JS, Hooper MH, Kelen GD, Khan A, Levine MA, Lewis RJ, Lindsell CJ, Marlin JS, McGlothlin A, Moore BL, Nugent KL, Nwosu S, Polito CC, Rice TW, Ricketts EP, Rudolph CC, Sanfilippo F, Viele K, Martin GS, Wright DW; VICTAS Investigators. Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial. JAMA. 2021 Feb 23;325(8):742-750. doi: 10.1001/jama.2020.24505.

  PMID: 33620405 DERIVED

• Lindsell CJ, McGlothlin A, Nwosu S, Rice TW, Hall A, Bernard GR, Busse LW, Ely EW, Fowler AA, Gaieski DF, Hinson JS, Hooper MH, Jackson JC, Kelen GD, Levine M, Martin GS, Rothman RE, Sevransky JE, Viele K, Wright DW, Hager DN. In response: Letter on update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol. Trials. 2020 Apr 22;21(1):351. doi: 10.1186/s13063-020-04290-6.

  PMID: 32317004 DERIVED

• Morgan J. Surviving sepsis and intensive care unit delirium: a remarkable recovery. Lancet Respir Med. 2020 Mar;8(3):241-242. doi: 10.1016/S2213-2600(20)30043-6. Epub 2020 Jan 30. No abstract available.

  PMID: 32007132 DERIVED

• Lindsell CJ, McGlothlin A, Nwosu S, Rice TW, Hall A, Bernard GR, Busse LW, Ely EW, Fowler AA, Gaieski DF, Hinson JS, Hooper MH, Jackson JC, Kelen GD, Levine M, Martin GS, Rothman RE, Sevransky JE, Viele K, Wright DW, Hager DN. Update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol: statistical analysis plan for a prospective, multicenter, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial. Trials. 2019 Dec 4;20(1):670. doi: 10.1186/s13063-019-3775-8.

  PMID: 31801567 DERIVED

• 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.

  PMID: 30953543 DERIVED

MeSH Terms

Conditions

Sepsis

Interventions

Ascorbic Acid; Thiamine; thiamine hydrochloride; Hydrocortisone

Condition Hierarchy (Ancestors)

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

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

Results Point of Contact

• Title: Jon Sevransky MD, MHS
• Organization: Emory University

jonathan.sevransky@emoryhealthcare.org

404-778-5734

Study Officials

• Jonathan Sevransky, MD, MHS

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 10, 2018
• First Posted: April 26, 2018
• Study Start: August 22, 2018
• Primary Completion: August 22, 2019
• Study Completion: January 29, 2020
• Last Updated: April 13, 2021
• Results First Posted: September 18, 2020

Record last verified: 2021-03

Locations

US (43)