Clinical trial NCT04138394: VItamin C in Thermal injuRY: The VICToRY Trial
Official title: VItamin C in Thermal injuRY: The VICToRY Trial A Phase III Multi-center Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Shock
Thermal Burn
Lead sponsor: Clinical Evaluation Research Unit at Kingston General Hospital
Sponsor class: OTHER
Collaborators: name: Dr. Christian Stoppe, MD, Co-Principal Investigator, Wurzburg University, Wurzburg, Germany
First posted: 2019-10-24
Enrollment: 666
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Patients will be allocated to receive intravenous vitamin C at 50mg/kg, every 6 hrs for 96 hrs or placebo. We justify this proposed dosing strategy as the proposed dose of vitamin C has been shown to be safe and effective in patients with sepsis and lung injury whereas prior dosing strategies used in the burns literature (66 mg/kg/24 hours) have safety issues and are not long enough in duration. Control group: patients will receive a similar amount of placebo (either D5W or saline) delivered in the same manner as the vitamin C.
Primary purpose: TREATMENT

Brief summary: This study aims to show that giving high dose, intravenous vitamin C in addition to standard care to burned critically ill patients will be associated with less organ dysfunction, improved survival and a quicker rate of recovery. In this study, all patients will receive standard care and of the patients will also receive high dose intravenous vitamin C, while the other half of patients will receive placebo.

Detailed description: In certain disease states, such as those associated with severe burns and other critical illnesses, the relationship between nutrient deficiencies, altered immune status, and acquired infection has been recognized for many years. More than in any other injury, the inflammation and catabolism associated with severe burns can exacerbate nutrient deficiencies, thereby predisposing patients to impaired immune function and increased risk of developing infectious complications, organ dysfunction, and death.

We aim to conduct a large-scale, multi-center randomized trial to evaluate the effect of high-dose (50mg/kg every 6 hours for 96 hours) intravenous vitamin C in addition to standard of care (SOC) on 28-days composite outcome of Persistent Organ Dysfunction (POD) and all-cause mortality compared to add-on placebo and SOC.

Patients will be allocated to 2 groups, active or control: patients in the active group will receive intravenous vitamin C at 50mg/kg every 6 hrs for 96 hrs. Patients in the control group will receive a similar amount of placebo (either D5W or saline) delivered in the same manner as the vitamin C. This study will be the first large international multi-centre trial examining the effects of high dose intravenous vitamin C in burn patients. It represents a unique collaboration of burn units worldwide that is coordinated by the Clinical Evaluation Research Unit, based in Kingston Ontario Canada, a coordinating center that has demonstrated the ability to run multi-center trials and translate findings into practice.

Eligibility criteria: Inclusion Criteria:

* 18 years of age or older
* Deep 2nd and/or 3rd degree burns requiring skin grafting
* Minimum burn size of ≥ 20% Total Body Surface Area (TBSA)

Exclusion Criteria:

* \>24 hours from admission to participating hospital to consent.
* Patients admitted to burn unit \>24 from injury or accident.
* Patients who are moribund (not expected to survive the next 72 hours).
* Pregnancy (pregnancy will be ruled out as part of standard of care) or lactating.
* Enrollment in another industry sponsored ICU intervention study.
* Receiving high-dose IV vitamin C already (enteral or oral vitamin C is allowed).
* Known glucose-6-phosphate dehydrogenase (G6PD) deficiency.
* Recent history of kidney stones (within the last year).
* Concomitant use of hydroxycobalamin (vitamin B12) for suspected cyanide poisoning.

Primary outcomes:
measure: Persistent Organ Dysfunction + Death
timeFrame: at 28 days
measure: Time to discharge alive from hospital
timeFrame: 90 days
Secondary outcomes:
Other outcomes:
measure: ICU length of stay
timeFrame: 90 days
measure: Duration of mechanical ventilation
timeFrame: 90 days
measure: ICU readmission rate
timeFrame: 90 days
measure: Hospital mortality
timeFrame: 90 days
measure: Hospital length of stay
timeFrame: 90 days
measure: Wound healing
timeFrame: 90 days
measure: Gram negative bacteremia
timeFrame: 90 days
measure: 6 month mortality
timeFrame: 6 months
measure: Health-related quality of life
timeFrame: 6 months
Locations:
city: Phoenix
country: United States
facility: Arizona Burn Center Valleywise Health
state: Arizona
city: Bridgeport
country: United States
facility: Bridgeport Hospital
state: Connecticut
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Saint Louis
country: United States
facility: Mercy Hospital St. Louis
state: Missouri
city: Ohio City
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center - Houston
state: Texas
city: Seattle
country: United States
facility: Harborview Medical Center - Seattle
state: Washington
city: Milwaukee
country: United States
facility: Ascension Columbia St. Mary's
state: Wisconsin
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
state: Hainaut
city: Ghent
country: Belgium
facility: Ghent University Hospital
state: Oost Vlaanderen
city: Brussels
country: Belgium
facility: Belgium Military Hospital, Military Hospital
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liege
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton General Hospital, Hamilton Health Sciences Corporation
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre, Ross Tilley Burn Centre
state: Ontario
city: Montréal
country: Canada
facility: Centre de recherche du CHUM
state: Quebec
city: Québec
country: Canada
facility: CHU de Québec-Université Laval, Hôpital de l'Enfant-Jésus
city: San José
country: Costa Rica
facility: Hospital San Juan de Dios
city: Tübingen
country: Germany
facility: BG Klinik Tübingen
state: Baden-Württemberg
city: Leipzig
country: Germany
facility: Klinikum St. George
state: Saxonia
city: Aachen
country: Germany
facility: RWTH Aachen University, Aachen
city: Cologne
country: Germany
facility: Merheim Medical Center, Hospitals of Cologne
city: Ludwigshafen
country: Germany
facility: Berufsgenossenschaftliche Unfallklinik Ludwigshafen
city: Würzburg
country: Germany
facility: University Hospital Würzburg
city: San Luis Potosí
country: Mexico
facility: Hospital Central Dr. Ignacio Morones Prieto
city: Asunción
country: Paraguay
facility: Centro Nacional del Quemado y Cirugías Reconstructivas
city: Bangkok
country: Thailand
facility: Siriraj Hospital, Mahidol University
city: Chelsea
country: United Kingdom
facility: Chelsea and Westminster Hospital
state: London
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
state: Mindelsohn Way
city: Prescot
country: United Kingdom
facility: St Helens and Knowsley Hospitals NHS Trust
city: Wakefield
country: United Kingdom
facility: The Mid Yorkshire Hospitals NHS Trust
Study officials:
affiliation: Queen's University
name: Daren K Heyland, MD
role: PRINCIPAL_INVESTIGATOR
References: