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Vitamin C–based regimens in sepsis plausible, need more data, expert says


 

EXPERT ANALYSIS FROM CHEST 2019

– While further data are awaited on the role of vitamin C, thiamine, and steroids in sepsis, there is at least biologic plausibility for using the combination, and clinical equipoise that supports continued enrollment of patients in the ongoing randomized, controlled VICTAS trial, according to that study’s principal investigator.

Jon Sevransky, MD, professor of medicine at Emory University in Atlanta, Ga

Dr. Jon Sevransky

“There is tremendous biologic plausibility for giving vitamin C in sepsis,” said Jon Sevransky, MD, professor of medicine at Emory University in Atlanta. But until more data are available on vitamin C–based regimens, those who choose to use vitamin C with thiamine and steroids in this setting need to ensure that glucose is being measured appropriately, he warned.

“If you decide that vitamin C is right for your patient, prior to having enough data – so if you’re doing a Hail Mary, or a ‘this patient is sick, and it’s probably not going to hurt them’ – please make sure that you measure your glucose with something that uses whole blood, which is either a blood gas or sending it down to the core lab, because otherwise, you might get an inaccurate result,” Dr. Sevransky said at the annual meeting of the American College of Chest Physicians.

Results from the randomized, placebo-controlled Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) trial may be available within the next few months, according to Dr. Sevransky, who noted that the trial was funded for 500 patients, which provides an 80% probability of showing an absolute risk reduction of 10% in mortality.

The primary endpoint of the phase 3 trial is vasopressor and ventilator-free days at 30 days after randomization, while 30-day mortality has been described as “the key secondary outcome” by Dr. Sevransky and colleagues in a recent report on the trial design.

Clinicians have been “captivated” by the potential benefit of vitamin C, thiamine, and hydrocortisone in patients with severe sepsis and septic shock, as published in CHEST in June 2017, Dr. Sevransky said. In that study, reported by Paul E. Marik, MD, and colleagues, hospital mortality was 8.5% for the treatment group, versus 40.4% in the control group, a significant difference.

That retrospective, single-center study had a number of limitations, however, including its before-and-after design and the use of steroids in the comparator arm. In addition, little information was available on antibiotics or fluids given at the time of the intervention, according to Dr. Sevransky.

In results of the CITRIS-ALI randomized clinical trial, just published in JAMA, intravenous administration of high-dose vitamin C in patients with sepsis and acute respiratory distress syndrome (ARDS) failed to significantly reduce organ failure scores or biomarkers of inflammation and vascular injury.

In an exploratory analysis of CITRIS-ALI, mortality at day 28 was 29.8% for the treatment group and 46.3% for placebo, with a statistically significant difference between Kaplan-Meier survival curves for the two arms, according to the investigators.

That exploratory result from CITRIS-ALI, however, is indicative of “something that needs further study,” Dr. Sevransky cautioned. “In summary, I hope I told you that biologic plausibility is present for vitamin C, thiamine, and steroids. I think that, and this is my own personal opinion, that evidence to date allows for randomization of patients, that there’s current equipoise.”

Dr. Sevransky disclosed current grant support from the Biomedical Advanced Research and Development Authority (BARDA) and the Marcus Foundation, as well as a stipend from Critical Care Medicine related to work as an associate editor. He is also a medical advisor to Project Hope and ARDS Foundation and a member of the Surviving Sepsis guideline committees.

SOURCE: Sevransky J et al. Chest 2019.

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