Efficacy and Safety of the Platelet-Activating Factor Receptor Antagonist BN 52021 (Ginkgolide B) in Patients with Severe Sepsis : A Randomised, Double-Blind, Placebo-Controlled, Multicentre Trial.

OBJECTIVE

To evaluate the efficacy and safety of the natural platelet-activating factor receptor antagonist, BN 52021 (ginkgolide B) in the treatment of patients with severe sepsis related to Gram-negative and mixed bacterial infection.

DESIGN AND SETTING

Prospective, randomised, double-blind, placebo-controlled, multicentre study carried out in 13 academic medical intensive care centres in Germany with up to 14 patients per centre.

PATIENTS

88 patients with severe sepsis under standard medical and surgical care: nine patients with pure Gram-positive infection, 79 patients with Gram-negative or mixed bacterial infections (subgroup for which efficacy was to be established).

INTERVENTIONS

Patients were randomised to receive either placebo or BN 52021 1.25 mg/kg bodyweight intravenously every 12h over a 4-day period in addition to their standard medical and surgical care.

MAIN OUTCOME MEASURES AND RESULTS

The primary efficacy variable was the 28-day all-cause mortality rate. The treatment groups were similar with respect to demographic data and prognostic factors influencing the outcome except for bodyweight and adequacy of antibiotic therapy. Analysis of patients with Gram-negative or mixed bacterial infection, for which efficacy was to be established, resulted in a 28-day all-cause mortality of 42.5% in the placebo group (n = 40; 17 deaths) versus 38.5% in the BN 52021 group (n = 39; 15 deaths). Among all randomised patients, the 28-day all-cause mortality rate was 40.9% in the placebo group (n = 44; 18 deaths) and 38.6% in the BN 52021 group (n = 44; 17 deaths). There were no differences in frequency and severity of adverse events between the two treatment groups.

CONCLUSIONS

Four-day administration of BN 52021 failed to demonstrate a statistically significant reduction in mortality in patients with severe sepsis suspected or confirmed to be related to infections other than Gram-positive bacterial infection.