Human recombinant activated protein C for severe sepsis

Area of Science:

• Critical Care Medicine
• Pharmacology
• Clinical Trials

Background:

• Sepsis is a life-threatening condition with high mortality rates.
• Novel therapeutic strategies are crucial for improving sepsis outcomes.
• Human recombinant activated protein C (APC) has been investigated as a potential sepsis therapy.

Purpose of the Study:

• To evaluate the clinical effectiveness of APC in treating patients with severe sepsis or septic shock.
• To synthesize evidence from randomized controlled trials (RCTs) on APC's efficacy and safety.

Main Methods:

• Comprehensive literature search of multiple databases (CENTRAL, MEDLINE, EMBASE, LILACS) and direct contact with researchers.
• Inclusion of four RCTs involving 4911 participants (adults and children, excluding neonates).
• Independent study selection, quality assessment, and data extraction using random-effects models and heterogeneity assessment (I²).

Main Results:

• APC did not significantly reduce 28-day mortality in adult severe sepsis patients (RR 0.92, 95% CI 0.72-1.18).
• No clear association between APC effectiveness and sepsis severity (APACHE II score).
• APC use was linked to a statistically significant higher risk of bleeding (RR 1.48, 95% CI 1.07-2.06).

Conclusions:

• Current evidence does not support the use of APC for treating severe sepsis or septic shock.
• APC is associated with an increased risk of bleeding complications.
• Further RCTs are needed to confirm any potential treatment effect; current promotion of APC is not advised.