Early administration of hydrocortisone, vitamin C, and thiamine in adult patients with septic shock: a randomized controlled clinical trial
What this study found
Early hydrocortisone, vitamin C, and thiamine did not improve survival or key clinical recovery outcomes in adult septic shock. Ninety-day mortality was 40.4% (86/213) with the intervention versus 39.0% (83/213) with placebo in ITT analysis (HR 1.08; 95% CI 0.80-1.46; P = 0.62), with similar null findings in PP analysis. There were also no meaningful differences in 28-day, ICU, or hospital mortality, shock reversal, time to shock reversal, or ICU-free days. Blood glucose disturbance was more common with the intervention (12.7% [27/213] vs 0.0%; P < 0.001).
- Study & population
- Randomized, placebo-controlled clinical trial in adults with septic shock diagnosed within 12 hours and treated in a single ICU at Northern Jiangsu People's Hospital in Yangzhou, China.
- Intervention
- The active regimen combined hydrocortisone 200 mg daily by continuous intravenous infusion over 24 h, vitamin C 2 g every 6 h, and thiamine 200 mg every 12 h.
- Key limitation
- Single-center trial in a Chinese Han ICU population, which limits generalizability.
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Open PDFOriginal abstract
Background The combination therapy of hydrocortisone, vitamin C, and thiamine has been proposed as a potential treatment in patients with sepsis and septic shock. However, subsequent trials have reported conflicting results in relation to survival outcomes. Hence, we performed this randomized controlled trial (RCT) to evaluate the efficacy and safety of early combination therapy among adult patients with septic shock. Methods This single-center, double-blind RCT enrolled adult patients with diagnosis of septic shock within 12 h from Northern Jiangsu People's Hospital between February 2019 and June 2021. Recruited patients were randomized 1:1 to receive intervention (hydrocortisone 200 mg daily, vitamin C 2 g every 6 h, and thiamine 200 mg every 12 h) or placebo (0.9% saline) for 5 days or until ICU discharge. The primary endpoint was 90-day mortality. The secondary endpoints included mortality at day 28, ICU discharge, and hospital discharge; shock reversal; 72-h Delta SOFA score; ICU-free days, vasopressor-free days, and ventilator support -free days up to day 28; ICU length of stay (LOS) and hospital LOS. Results Among 426 patients randomized, a total of 408 patients with septic shock were included in the per-protocol (PP) analysis, of which 203 were assigned to the intervention group and 205 to the placebo group. In the PP population, the primary outcome of 90-day mortality was 39.9% (81/203) and 39.0% (80/205) in the intervention and the placebo groups, respectively, and was not significantly different ( P = 0.86). There was no significant difference between two groups in 28-day mortality (36.5% vs. 36.1%, P = 0.94) or the ICU mortality (31.5% vs. 28.8%, P = 0.55) and hospital mortality (34.5% vs. 33.2%, P = 0.78). No other secondary outcomes showed significant differences between two groups, including shock reversal, vasopressor-free days, and ICU LOS. Intention-to-treat analysis included all the 426 patients and confirmed these results (all P > 0.05). Conclusion Among adult patients with septic shock, early use of hydrocortisone, vitamin C, and thiamine combination therapy compared with placebo did not confer survival benefits. Trial registration ClinicalTrials.gov: NCT03872011 , registration date: March 12, 2019. Graphic Abstract