Vitamin C Study Fails to Improve Sepsis Outcomes

 

A new study published in JAMA suggests that treatment with vitamin C, in addition to thiamine and hydrocortisone, does not improve treatment outcomes in hospitalized patients with sepsis.

The findings from this study slash hopes that vitamin C, a once-promising treatment option for sepsis, may hold little clinical value for the management of this life-threatening complication.

In the multicenter, randomized, placebo-controlled study, hospitalized patients with sepsis-induced respiratory and/or cardiovascular dysfunction (median age=62 years) were randomly assigned to a treatment regimen consisting of 1.5 g vitamin C, 100 mg thiamine, and 50 mg hydrocortisone every 6 hours (n=252) or a matching placebo (n=249).

The assigned treatments were administered over a 96-hour period or until discharge or death. All participants in the study had the option of being treated with open-label corticosteroids, with 33% of patients in the intervention group and 32% of patients in the control group exercising this option.

There was no difference between the vitamin C and placebo arms in regard to the primary outcome of ventilator- and vasopressor-free days (median=25 vs. 26 days, respectively; median difference=−1 day; 95% CI, −4-2 days; p=0.85). The 30-day mortality rate was also similar between the intervention (22%) and placebo (24%) groups.

Due to administrative reasons, the trial was terminated early, with the researchers suggesting it “may have been underpowered to detect a clinically important difference” between the groups.

This trial, led by Dr. Jonathan Sevransky, researcher and critical care physician at Emory University, was one of the largest to date that reported disappointing results with the use of vitamin C in sepsis.

In an interview with NPR, Sevransky noted that there have been three other completed randomized trials, none of which demonstrated a difference between intervention and control.

“We can say with some confidence that if there were such a large effect, we would have seen that in our patients,” he said.

Sevransky said that a large study in Canada is currently underway, noting this study may detect a smaller effect of a vitamin C-based regimen, but there are still no guarantees on its efficacy.

Even a modest effect would be promising, however, given sepsis is a life-threatening post-infection complication that affects approximately 1.7 million people in the U.S. each year. Approximately 20% to 30% of people with sepsis succumb to the disease.

Dr. Paul Marik, a critical care specialist at Eastern Virginia Medical school, previously published claims that the same treatment regimen could work for improving outcomes in patients with sepsis but only if it is administered very early in the clinical course. “”Some people think the matter is dead,” Marik said in an interview with NPF. “We would disagree.”

He added that the study by Sevransky and colleagues should have been an emergency department study, rather than a study focused on patients who were also in the intensive care unit (ICU).

“Once you’ve waited until they get to the ICU you’ve missed the boat,” he added.

Currently, doctors in Belgium are conducting a study utilizing the vitamin C, thiamine and hydrocortisone regimen in patients with sepsis in the emergency department to determine its benefits when given earlier.

Due to the conflicting data, doctors are now faced with a dilemma of whether or not to administer this vitamin C-based regimen in patient with sepsis.

“What if the drug has no demonstrable treatment benefit but doesn’t show any harm?” asked Dr. Christopher Seymour, critical care specialist at the University of Pittsburgh, also interviewed by NPR. “Should we just give it with the hope that if the ‘kitchen sink’ is thrown at the patient there will be a benefit? I don’t think so, in part because that distracts us from the science and the clinical care that might actually be making a difference.”

The dilemma reflects those faced by doctors treating patients with COVID-19. Early findings on experimental COVID-19 treatments, like convalescent plasma, suggested strong benefits for improving COVID-19-related outcomes, but definite conclusions on these therapies have yet to be made.