Vitamin C, steroids, thiamine for septic shock: no benefit in ACTS trial
A combination of vitamins C and B1 with corticosteroids didn't prevent organ failure in septic shock, the ACTS trial showed. The intervention improved the Sequential Organ Failure Assessment (SOFA) score 4.7 points compared with a 4.1-point improvement with placebo over the 72 hours after enrollment, which was not significant at P=0.12 for interaction, reported Michael Donnino, MD, of Beth Israel Deaconess Medical Center in Boston, and colleagues in JAMA. Kidney failure and 30-day mortality, if anything, went numerically against the regimen of 4 days on an IV of 1,500-mg parenteral ascorbic acid, 50-mg hydrocortisone, and 100-mg thiamine every 6 hours. The researchers concluded that the combination doesn't merit routine use. "There's been a tremendous amount of interest in vitamin C as a treatment for sepsis, based largely on a small, single-center observational study. But we've now got three decently-sized randomized controlled trials, all in agreement: vitamin C does not reverse organ failure in sepsis," commented critical care physician Robert Dickson, MD, of the University of Michigan School of Medicine in Ann Arbor. The VITAMINS trial showed no advantage in recovery from septic shock and numerically higher mortality with a vitamin C-hydrocortisone-thiamine combination. The CITRIS-ALI trial showed no impact on SOFA scores from high-dose IV vitamin C. "If the signal of benefit for vitamin C was anywhere near as strong as was initially suggested, it shouldn't be this hard to detect it in clinical trials," Dickson added. The researchers noted that vitamin C has also been proposed for treating respiratory failure from COVID-19, as was seen in a recent case report. However, Dickson said, "the data supporting use of vitamin C in sepsis were already weak. The data supporting its use in COVID-19 are non-existent." The ACTS trial included 205 adults with septic shock randomized at 14 U.S. medical centers (mean age 68, 44% women). Other treatment followed local sepsis management guidelines, with recommendation of early antibiotics, keeping mean arterial pressure to at least 65 mm Hg with a combination of volume resuscitation and vasopressors, and early treatment of the source of infection. Among secondary endpoints, incidence of kidney failure was 31.7% with the intervention versus 27.3% with placebo (P=0.58). Mortality at 30 days was 34.7% and 29.3%, respectively, for a hazard ratio of 1.3 for the intervention (P=0.26). Median ventilator-free days in the first week after enrollment was 6 in both groups, but shock-free days was 5 with intervention versus 4 without, which did reach statistical significance. Cardiovascular SOFA score also favored the intervention by 0.5 points (P=0.03 for interaction). Those two findings should be considered hypothesis generating, given the number of comparisons made, the researchers cautioned. Serious adverse events were similar between groups. Limitations included not selecting patients on the basis of vitamin deficiency and exclusion of patients with ongoing or planned corticosteroid use, which might have been a group more likely to benefit from it.
The trial was supported by a grant from Open Philanthropy. Donnino disclosed support from the NIH.
by Crystal Phend, Senior Editor, MedPage Today August 18, 2020