APROCCHSS
Trial question
What is the role of hydrocortisone and fludrocortisone in adult patients with septic shock?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
33.0% female
67.0% male
N = 1241
1241 patients (415 female, 826 male)
Inclusion criteria: patients with septic shock
Key exclusion criteria: presence of septic shock for at least 24 hours, a high risk of bleeding, pregnancy or lactation, underlying conditions that could affect short-term survival, or previous treatment with corticosteroids
Interventions
N=614 hydrocortisone and fludrocortisone (hydrocortisone 50 mg IV q6h plus fludrocortisone 50 µg via nasogastric tube once daily)
N=627 placebo (matching placebo)
Primary outcome
Death at 90 days
43
49
49.0 %
36.8 %
24.5 %
12.3 %
0.0 %
Hydrocortisone and fludrocortisone
Placebo
Significant decrease ▼
NNT = 16
Significant decrease in death at 90 days (43% vs. 49%; RR 0.88, 95% CI 0.08 to 1.68)
Secondary outcomes
No significant difference in death at 28 days (34% vs. 39%; RR 0.87, 95% CI 0.75 to 1.01)
Significant decrease in ICU mortality (35% vs. 41%; RR 0.86, 95% CI 0.75 to 0.99)
Significant decrease in in-hospital mortality (39% vs. 45%; RR 0.86, 95% CI 0.76 to 0.98)
Safety outcomes
No significant differences in serious adverse events, bleeding, rate or site of superinfection, new-onset sepsis or septic shock, or neurologic sequelae.
Significant difference in hyperglycemia (89% vs. 83%).
Conclusion
In patients with septic shock, hydrocortisone and fludrocortisone were superior to placebo with respect to death at 90 days.
Reference
Djillali Annane, Alain Renault, Christian Brun-Buisson et al. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med. 2018 Mar 1;378(9):809-818.
Open reference URL