Combination vitamin C, hydrocortisone and thiamine no better than hydrocortisone alone for resolution of septic shock, study suggests
In this novel randomized controlled trial, investigators have evaluated the comparative effectiveness of combination vitamin C, hydrocortisone and thiamine versus hydrocortisone alone for the treatment of septic shock. Researchers have determined that both regimens are seemingly equally effective.
Led by investigators from Monash University (Melbourne, Australia), an international team of researchers has conducted a new randomized controlled trial evaluating the comparative effectiveness of combination vitamin C, hydrocortisone and thiamine versus hydrocortisone alone for the treatment of septic shock. The results of the study suggest that both treatment regimens are equally effective.
Sepsis is a life-threatening condition responsible for over 5 million deaths worldwide each year; it is characterized by an abnormal host response to infection and contributes to approximately one-third of hospital deaths.
A relatively small randomized clinical trial recently demonstrated that high-dose, intravenous vitamin C may function as an effective adjunct therapy for the treatment of septic shock, likely due its anti-inflammatory and -oxidant properties. Further, as thiamine deficiency has been reported in approximately one-fifth of individuals with sepsis, the effectiveness of combination vitamin C, hydrocortisone and thiamine as a treatment for septic shock has sparked much interest.
Indeed, a recent retrospective study demonstrated that the combination intervention was associated with both reduced time on vasopressor medication and hospital mortality amongst individuals with sepsis or septic shock.
Now, for the first time, researchers have investigated the comparative effectiveness of combination vitamin C, hydrocortisone and thiamine versus hydrocortisone alone – which has itself been demonstrated effective at accelerating sepsis recovery – for the treatment of septic shock.
In this open-label, randomized clinical trial – conducted across ten intensive care units in Australia, New Zealand and Brazil – 211 patients, who met the Sepsis-3 definition criteria for septic shock diagnosis, were randomized to receive either combination intravenous vitamin C, hydrocortisone and thiamine, or intravenous hydrocortisone alone. Treatment was administered for up to 10 days, or until septic shock recovery. The primary study outcome was duration of time alive and free of vasopressor administration for up to 7 days. Various secondary study outcomes, including 90-day mortality rates were also specified.
Amongst individuals randomized to the intervention study group, who received the combination regimen, time alive and vasopressor free up to 7 days was 122.1 hours. Similarly, this time was 124.6 hours for participants in the control group who were administrated hydrocortisone alone. Further, nine of the ten specified secondary outcomes of the study showed no statistically significant differences between intervention and control group measurements.
In the study, the authors concluded: “The finding suggests that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone.”
Fujii T, Luethi N, Young PJ et al. Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock. JAMA. doi:10.1001/jama.2019.22176 (2020) (Epub ahead of print);