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ACTS RCT – Ascorbic Acid, Corticosteroids, Thiamine for Septic Shock

October 6, 2020

Written by Clay Smith

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There was no benefit of ascorbic acid, hydrocortisone, and thiamine on improving 72-hour SOFA score in adults with septic shock.

Why does this matter?
We have covered this before, from the original case report of this weird sepsis cocktail, to CITRUS ALI, to HYVCTTSSS, to VITAMINS, to VITAMINS for kids, to ORANGES. Is this the final ACT?

If I see another paper on this, I’m gonna ACT out…
This was a multicenter RCT that enrolled 205 adults with septic shock to receive, “parenteral 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).” They found no difference in the primary outcome, improvement in SOFA score over the first 72 hours: -4.7 points (treatment) vs -4.1 points (placebo); adjusted difference, -0.8 (95%CI -1.7 to 0.2). There was also no difference in kidney failure or 30-day mortality in the treatment group; in fact, mortality was numerically, though not statistically, greater in the treatment arm. The treatment group vs placebo had more adverse events: hyperglycemia (12 vs 7 patients), hypernatremia (11 vs 7 patients), and new hospital-acquired infection (13 vs 12 patients). Interestingly, 4,569 patients were assessed for eligibility; 4,364 were excluded. A large number of patients, 3,514, were excluded because steroids had already been started or steroid use was planned. It’s a concern when it feels like such a select, almost hand-picked, group of patients were included for analysis – remember the PARACHUTE RCT. This may have blunted the potential impact of the treatment cocktail, since it only included patients whom the doctors thought would not need steroids. This may also impact the generalizability of the results. Regardless, this study did not show benefit with the sepsis cocktail, and neither have the other RCTs. I just don’t think vitamin C+hydrocortisone+thiamine is the magic bullet.

Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial. JAMA. 2020 Aug 18;324(7):642-650. doi: 10.1001/jama.2020.11946.

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