Adding Vitamin C and Thiamine Doesn't Outperform Hydrocortisone Alone For Sepsis Treatment

The current standard-of-care for sepsis includes fluid resuscitation, antibiotics, and blood pressure support. But clinicians lack a tried-and-true therapy to decrease mortality and according to a recent study, global sepsis deaths may be occurring more frequently.

Some clinicians were hopeful that a combination of vitamin C, hydrocortisone, and thiamine might make for a more effective sepsis therapy than hydrocortisone alone. Unfortunately, investigators of a new study published in JAMA have found that this combination does not appear to significantly improve time alive or time free of vasopressor administration among patients with sepsis.

Results were gathered through a multicenter, open-label, randomized clinical trial conducted in 10 intensive care units in Brazil, Australia, and New Zealand.

The primary outcome was duration of time alive and time free of vasopressor administration up to day 7. Secondary outcomes of 28 and 90-day mortality were prespecified as well.

A total of 216 patients who fulfilled the Sepsis-3 definition of septic shock were enrolled between May 2018 and July 2019, with a final follow-up date of October 6, 2019.

The intervention group consisted of 109 patients who received 1.5 g of intravenous vitamin C and 50 mg of hydrocortisone every 6 hours, as well as 200 mg of thiamine every 12 hours.

The control group consisted of 107 patients administered intravenous hydrocortisone every 6 hours. Patients were studied until shock resolution or for up to 10 days of treatment.

Among the 216 patients randomized, 211 consented to the trial and completed the primary outcome measurement. The mean age of patients was 61.7 years. According to the abstract 63% of participants were male.

Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR] 76.3-145.4 hours) in the intervention group, compared with 124.6 hours (IQR 82.1-147.0 hours) in the control group.

Secondary outcome results were also similar between the intervention and control group. There was no significant difference between groups for all-cause mortality at 28 days after randomization, at 22.6% and 20.4% all-cause mortality in the intervention and control groups, respectively.

Likewise, there was no significant difference in 90-day all-cause mortality between groups, at 28.6% and 24.5% all-cause mortality for the intervention and control groups, respectively.

The introduction of the intervention combination therapy did not appear to provide benefit or harm. None of the positive findings observed in a previous single-center before-after study were able to be replicated.

The study results appear to indicate that the search for improved sepsis treatments will have to continue, given patients treated with the intervention combination did not see significantly better outcomes.

“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,” study authors concluded.