Vitamin C infusion does not stave off death, organ dysfunction in ICU-admitted patients with sepsis

The administration of intravenous vitamin C to patients with sepsis admitted to the intensive care unit (ICU) did not result in a reduced risk of death or organ dysfunction, according to results of the phase III LOVIT* trial.

Participants in this international trial (35 ICUs in Canada, New Zealand, and France) were 872 adults (mean age 65 years) who had been admitted to the ICU for ≤24 hours due to proven or suspected infection and who were receiving vasopressors. They were randomized 1:1 to receive intravenous infusions of vitamin C (50 mg/kg) or placebo every 6 hours for ≤96 hours while they were in the ICU.

Median duration of ICU stay was 6 days and median duration of hospitalization 16 days. Mean APACHE** II and SOFA** scores at baseline were 24 and 10, respectively. Most patients (>70 percent) scored between 1 and 4 on the Clinical Frailty Scale. About 45–46 percent of patients received glucocorticoids and 65–69 percent mechanical ventilation.

At day 28, the composite of death or persistent organ dysfunction*** was increased among patients who received vitamin C vs placebo (44.5 percent vs 38.5 percent; risk ratio [RR], 1.21, 95 percent confidence interval, 1.04–1.40; p=0.01). [N Engl J Med 2022;386:2387-2398]

At day 28, a greater proportion of patients assigned to vitamin C than placebo died (35.4 percent vs 31.6 percent; RR, 1.17, 95 percent CI, 0.98–1.40) or experienced persistent organ dysfunction (9.1 percent vs 6.9 percent; RR, 1.30, 95 percent CI, 0.83–2.05). The median number of days without organ dysfunction was 17 and 19.5 in the vitamin C and placebo groups, respectively (median difference -2.43 days). SOFA score at day 28 did not differ between groups (6.5 vs 7.9)

At 6 months, 45.8 and 43.4 percent of patients in the vitamin C and placebo groups, respectively, had died. Quality of life, as per European Quality of Life–5 Dimension 5-Level (EQ-5D-5L) visual-analogue scale score, was similar between groups at 6 months (65.8 vs 63.8).

A comparable proportion of patients in the vitamin C and placebo groups experienced stage 3 acute kidney injury (37.8 percent vs 37.9 percent). Hypoglycaemia occurred in 6.1 and 5.1 percent, respectively, with one incident in a vitamin C recipient considered serious, warranting “a protocol amendment requiring modifications in blood glucose monitoring in many centres”. There were no incidents of acute haemolysis. One patient in the vitamin C group experienced a serious adverse event (an anaphylactic reaction deemed possibly related to vitamin C infusion).

“Vitamin C … levels are low in many critically ill patients, which has increased the plausibility of benefit with supplementation,” said the investigators.

“[However,] among adults with sepsis in the ICU, high-dose intravenous vitamin C was found not to be a helpful treatment,” said study co-principal investigators Dr Neill Adhikari from the Sunnybrook Health Sciences Centre, Toronto, and Professor François Lamontagne from the Université de Sherbrooke, Quebec, Canada. [https://sunnybrook.ca/media/item.asp?c=1&i=2452&f=lovit-trial, accessed 31 August 2022]

“Importantly, we also found that study participants in the treatment group had a higher risk of death or persistent organ dysfunction at 28 days, compared to those who did not receive the treatment,” they added.

“Given this, we advise against using high-dose vitamin C to treat sepsis patients, unless they are part of a clinical trial,” they noted.