Burn injuries are a common cause of injury on the battlefield and in civilian life. All burn patients experience an initial injury, a healing process, and the long-term effects of injury, such as scars. But during the healing process, some patients (such as those with larger burns) experience additional problems, like too much inflammation and stress. Inflammation is the response of the body's infection- and injury-fighting white blood cells. Oxidative stress is caused by chemicals in the body that form in response to injury and that can cause additional damage. Too much inflammation and oxidative stress places burn patients at risk of organ failure, disability, and even death. More clinical studies are needed, to define better ways to reduce these risks and improve the outcomes of burn victims.

Vitamin C is a naturally occurring substance that can be found in many foods, such as oranges and tomatoes. Vitamin C has been called the most important antioxidant, which is a substance that can reduce inflammation and oxidative stress in severely injured patients. In a recent review performed by our group, vitamin C given in high doses to a general intensive care unit (ICU) population was associated with a significant reduction in mortality, and there were no safety problems. Admittedly, the evidence supporting vitamin C in burn patients is weak: Data come from one small trial published over 20 years ago. Moreover, high-dose vitamin C is not widely administered in burn units around the world. Thus, further trials testing vitamin C in burn patients are needed.

Consistent with the focus of the Military Burn Research Program's call for proposals on developing novel therapeutic interventions for the management of burn patients, this study aims to test whether vitamin C is useful in treating such patients. The amount of vitamin C the patients will receive in this trial is much higher than the amount normally eaten in food, and it will be given intravenously (IV). In this study, eligible patients with significant burn injury will receive a high dose of vitamin C (200 mg/kg/day) or a placebo (a solution of sugar or salt water) through an intravenous line 4 times a day for 96 hours (4 days), from the time they join the study or until they are discharged from the hospital, whichever comes first. Neither the patient nor the treatment team will know which treatment the patient is getting. We will monitor patients' progress to see if they are healing well and to see how long they stay in the ICU and hospital. We will then compare those that received vitamin C with those that did not to see if they developed fewer problems with their organs (kidneys, lung, and heart), a lower death rate, a shorter hospital length of stay, and an improvement in the quality of their lives 6 months later. This will enable us to determine the effect of this inexpensive, readily available, safe, therapeutic strategy.

We have an international burn research network that is currently piloting the study procedures, and we have shown this study protocol to be feasible. We have 40 burn units worldwide ready to help us enroll patients in this large multi-center trial so that a total of 666 patients are enrolled over the next 4 years.

The importance of this study is that we stand to demonstrate that a simple nutrient, vitamin C, can significantly impact the outcome of critically ill, burn-injured patients. If this trial is positive, we aim to ensure that this therapy is an option for severely injured burn patients worldwide, whether civilian or military. This will be one of the first treatments that can be delivered by medics on the battlefield that addresses the underlying effects of severe burn injury on the body as it meets the weight and size requirements for prehospital battlefield care.