Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock

Abstract

It is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock.OBJECTIVE To determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTSMulticenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019.INTERVENTIONS Patients were randomized to the intervention group (n = 109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n = 107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days. MAIN OUTCOMES AND MEASURESThe primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were prespecified, including 90-day mortality.RESULTS Among 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was -0.6 hours (95% CI, -8.3 to 7.2 hours; P = .83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported. CONCLUSIONS AND RELEVANCEIn patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. 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.

Myth Busters: Dietary Supplements and COVID-19

“…8 Similarly, the VITAMINS trial showed that a combination of IV vitamin C, hydrocortisone, and thiamine did not improve duration of time alive or free from vasopressor administration compared with hydrocortisone alone in a population with septic shock. 9 Physicians from China have stated on various media outlets that they have successfully treated more than 50 patients with moderate to severe COVID-19 with large doses of IV vitamin C (10 000-20 000 mg/d), leading to a shorter mean hospital length of stay compared with untreated patients with COVID-19 and no incidences of death. 10 Details of this evidence are unavailable because these findings have not (at the time of this writing) been published in either preprint or peer-reviewed journals.…”

Evaluating extremely low plasma ascorbate levels and reduction of plasma ascorbate levels by dialysis in Japanese hemodialysis patients

“…However, in a recent prospective case series exploring high-dose intravenous vitamin C (15-100 g) administration, increased vitamin C intake was not associated with any cases of symptomatic renal stones and kidney injury [34]. Moreover, significant side effects of vitamin C are not reported in any of the mentioned controlled trials, including the most recent VITAMIN randomized trial [35].…”

Is the VITAMINS RCT indicating potential redundancy between corticosteroids and vitamin C?

“…Since the publication of the retrospective before and after study by Dr. Marik and colleagues, in which administration of hydrocortisone, intravenous (IV) vitamin C, and thiamine was indicated to provide a survival advantage in septic patients [1], there has been a prevalence of clinical trials of variable quality and subsequent meta-analyses indicating variable outcomes [2]. Unlike previous combination trials, which did not control for corticosteroid use in the control arm, the recently published VITAMINS randomized clinical trial standardized corticosteroid administration in the control arm to determine if IV vitamin C and thiamine could provide an additional survival advantage over hydrocortisone alone [3]. This trial showed no benefit of the combination of hydrocortisone, IV vitamin C, and thiamine in comparison to hydrocortisone alone.…”