Early administration of hydrocortisone, vitamin C, and thiamine in adult patients with septic shock: a randomized controlled clinical trial

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. The active intervention arm included 213 participants randomized in ITT analysis and 203 participants analyzed in PP analysis; all patients were Chinese Han.

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. Vitamin C and thiamine were diluted in 100 mL 0.9% sodium chloride and infused intravenously over 60 min for 5 days or until ICU discharge, whichever came first, versus placebo.

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).

Single-center trial in a Chinese Han ICU population, which limits generalizability. Although randomized and placebo-controlled, the study did not show benefit on mortality or secondary outcomes, and the intervention was associated with more blood glucose disturbances. The findings do not support routine use of this combination for septic shock in similar settings, but applicability outside this population remains uncertain.