Posted January 13, 2023

Daren Heyland, MD, MSc., Queen’s University

Severe burn injuries are notoriously difficult to treat, owing to the disruption of the primary barrier between the environment and the body. This disruption causes pain and frequently leads to infection, disruptions in thermoregulation, and fluid imbalance. During Operation Iraqi Freedom and Operation Enduring Freedom, severe burns represented 5%-20% of all combat-related casualties.¹ It is expected that as combat operations transition to urban environments, multi-domain operations increase, and conflicts occur with peer and near-peer adversaries, the number of burn casualties will rise. Moreover, healing from burn injuries can be a long and arduous process, with some patients experiencing increased inflammation and oxidative stress that puts the individual at greater risk for multiple organ failure, disability, and death. Strategies to decrease inflammation and oxidative stress immediately after burn injury are urgently needed to mitigate secondary sequelae and improve both short- and long-term burn injury outcomes.

With support from the fiscal year 2021 Military Burn Research Program Clinical Translational Research Award – Clinical Trial Option, Dr. Daren Heyland and his co-principal investigators, Dr. Christian Stoppe and Dr. Leopoldo Cancio aim to assess the utility of high-dose intravenous vitamin C (HDVC) for the early initial treatment of burn patients in the context of a phase 3 double-blind multi-center randomized clinical trial. Vitamin C is an important, naturally occurring antioxidant that is widely commercially available and inexpensive. It has been shown to be therapeutically safe, with the potential to decrease oxidative stress damage in the body, reduce the volume of fluid required for burn resuscitation, optimize the bodies` own defense mechanisms and protect against burn-related organ injury in large-animal preclinical studies as well as small-scale clinical trials. Recently, Dr. Heyland’s group performed a meta-analysis, assessing HDVC in the general intensive care unit population, and found a significant reduction in mortality.² Evidence-based clinical evaluation of HDVC is a significant research gap within the burn care continuum; existing evidence is from small-scale trials and, therefore, administration of HDVC is not standard clinical practice globally.

In this large-scale, multi-center clinical trial, Dr. Heyland and co-investigators from 40 medical centers worldwide will recruit 666 patients with significant burn injuries, administer either HDVC or a placebo, and monitor patient outcomes. Each burn center will assess factors such as organ complications, morbidity rates, hospital length of stay, and quality of life post injury.

Once completed, the results of this study could support the use of HDVC as one of the first treatments that can be easily delivered early in the course of burn treatment to address and mitigate the underlying effects of burn injuries and its sequelae soon after injury. Advantageously, the vitamin C treatment has the potential to reduce the volume and weight of liquid that a medic must carry for burn resuscitation on the battlefield. This multi-center trial evaluating HDVC has the potential to change how burns are treated, both in the military and civilian population, and could impact the survival of critically ill, burn-injured patients and improve their quality of life.

References:
¹Engel C, McBain R, McBirney S, et al. 2020. The effect of blast-related burn injuries from prolonged field care to rehabilitation and resilience: A review of the scientific literature. Research Reports. RAND Corporation. Santa Monica, California. doi: 10.7249/RRA807-1.

²Patel JJ, Ortez-Reyes LA, Clarke J, Dhaliwal R, Hill A, Stoppe C, Lee ZY, Heyland DK. Intravenous Vitamin C in Critically Ill Patients: A Systematic Review and Meta-Analysis. Crit Care Med. 2021 Sep 22. doi: 10.1097/CCM.00000000000053202021.

Links:
Public and Technical Abstracts:  Vitamin C in Thermal Injury: The Victory Trial

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