Activation of the coagulation system and depletion of endogenous anticoagulants are frequently found in patients with severe sepsis and septic shock.
The diffuse microthrombus formation that can then result may induce organ dysfunction and lead to excess mortality in septic shock.
It has been hypothesized that Antithrombin III may provide protection from multiorgan failure and may improve survival in severely ill patients.
A multicenter phase III clinical trial in patients with severe sepsis (the KyberSept Trial) has now been conducted to test this theory.
The double-blinded, placebo-controlled study was designed to determine if high-dose antithrombin III, administered within 6 hours of onset, would provide a survival advantage in patients with severe sepsis and septic shock.
The trial was conducted between 1997 and 2000, and involved a total of 2314 adult patients.
| Antithrombin III does not benefit the treatment of septic shock and sepsis.
| Journal of the American Medical Association |
The patients were randomized into two equal groups of 1157, to receive either intravenous antithrombin III (30 000 IU in total over 4 days) or a placebo (1% human albumin).
The main outcome measured was all-cause mortality 28 days after initiation of study medication.
The research group found that overall mortality at 28 days in the antithrombin III group was 39%, compared to 38% in the placebo group.
Secondary end points, including mortality at 56 and 90 days, and survival time in the intensive care unit, did not differ between the antithrombin III and placebo groups.
In the subgroup of patients who did not receive concomitant heparin during the 4-day treatment phase (n = 698), the 28-day mortality was non-significantly lower in the antithrombin III group (38%) than in the placebo group (44%).
This trend became significant after 90 days (n = 686, 45% for antithrombin III treatment versus 53% of the placebo group).
However, in patients receiving antithrombin III and concomitant heparin, a significantly increased incidence of bleeding was observed.