ACTS Randomized Control Trial

A new trial called the ACTS randomized control trial has found that combination therapy with Vitamin C (ascorbic acid), corticosteroids, and thiamine did not show any significant benefit for the patients with septic shock. The recent study was published in the journal, JAMA Network, 2020.

The combination of Vitamin C, corticosteroids, and thiamine has been identified as a potential therapy for septic shock.

Sepsis is a highly morbid condition where antibiotics and source control remain the mainstay of treatment. Previous studies found that thiamine attenuated renal damage and thus mortality in septic patients. Other studies have also found that ascorbic acid improved clinical outcomes and corticosteroids had a synergistic effect on ascorbic acid levels. As the combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock, various researchers from different centers conducted a trial to determine the effect of the combination therapy with ascorbic acid, corticosteroids, and thiamine on the attenuation of organ injury in patients with septic shock.

The study was a randomized, blinded, multicenter clinical trial conducted between February 9, 2018, and October 27, 2019, at 14 centers in the United States and followed up till November 26, 2019. Two hundred five adult patients with septic shock were enrolled. Patients were randomly assigned two groups to receive parenteral Vitamin C (ascorbic acid) 1500 mg, hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102). The primary outcome was to measure the change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrolment and 72 hours and the secondary outcome of measurement was to check the kidney failure and 30-day mortality.

Key Findings of the Study

• Among 205 randomized patients, the mean age with SD was 68±15 years.
• Out of these, 90 were [44%] women.
• 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group).
• Overall, there was no statistically significant interaction between time and treatment group regarding SOFA score over the 72 hours after enrolment.
• There was no statistically significant difference in the incidence of kidney failure or 30-day mortality.
• The most common serious adverse events were hyperglycaemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively).

Thus, the trial concluded that in patients with septic shock, the combination of Vitamin C (ascorbic acid), corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrolment. Hence, by this data, the researchers did not support the routine use of this combination therapy for patients with septic shock.

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