Vit C fails to deliver- VITAMINS trial

Tomoko Fujii,  Nora Luethi,  Paul J. Young et al  published the results of   much awaited VITAMINS (The Vitamin C, Hydrocortisone and Thiamine in Patients With Septic Shock) trial.



It was an investigator-initiated, multicenter, open-label, parallel-group randomized trial comparing vitamin-C, thiamine and hydrocortisone to hydrocortisone alone in patients with septic shock.


10 intensive care units in Australia, New Zealand, and Brazil.


Adult patients with a diagnosis of septic shock based on Sepsis-3 consensus definition  of 24 hour duration.

Exclusion criteria included age younger than 18 years, a do-not-resuscitate order, imminent death, diagnosis of septic shock longer than 24 hours ago, known or suspected disease with a strong indication or contraindication for any of the study drugs, and another indication for hydrocortisone than septic shock.


Patients in the intervention group received IV vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours). Patients in the control group received IV hydrocortisone (50 mg every 6 hours).

The RCT compared the combination therapy in conjunction with usual care (intervention group; n = 109) vs hydrocortisone plus usual care (control group; n = 107).


Primary – Time alive and free of vasopressors at day 7.


28-day, 90-day, ICU, and hospital mortality, 28-day cumulative vasopressor-free days, 28-day cumulative mechanical ventilation-free days, 28-day renal replacement therapy–free days, change in SOFA score at day 3, 28-day ICU free-days, and hospital length of stay.


There was no significant difference in time alive and free of vasopressors up to day 7 (168 hours) after randomization between the intervention group and the control group (median, 122.1 hours [IQR, 76.3-145.4 hours] vs 124.6 hours [IQR, 82.1-147.0 hours], respectively.

Only secondary outcome where there was difference, was change in SOFA score at day 3. It  was significantly greater in the intervention group than in the control group (median, –2 [IQR, –4 to 0] vs –1 [IQR, –3 to 0], respectively; difference, –1.0 [95% CI, –1.9 to –0.1]; P = .02).


Absolute deficiencies of vitamin C and thiamine both cause severe disease (scurvy and beri beri). Relatively low levels are implicated in the pathogenesis of sepsis.Thiamine deficiency has also been reported in 20% of critically ill patients with sepsis. The combination of high-dose IV vitamin C and hydrocortisone together with thiamine was assessed in a single-center retrospective before-and-after study of 94 patients with severe sepsis or septic shock.  This trial showed improvement in mortality,  and created a lot of hype. However,  the results were too good to be true.  Given the hype,  several trials were planned.  At present, 37 trials are examining vitamin C as a treatment for sepsis in Asia, Africa, Europe, North America, and Latin America.

This trial showed an almost identical median time alive and free of vasopressors in the 2 study groups.

Prior to this, Vit C has been studied in 8 RCTs and 6 observational studies that reported data on all-cause mortality (mostly hospital and 28-day outcomes). Of the 8 RCTs, 6 (including a total of 633 patients) showed no significant effect of vitamin C on mortality.

So far, Vit C has not been proven of any value in sepsis.

We can wait for the reminder of studies.




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