Score-based immunoglobulin G therapy of patients with sepsis:: The SBITS study

Objective: Intravenous immunoglobulin as an adjunctive treatment in sepsis was regarded as promising by a Cochrane meta-analysis of smaller trials. In this phase III multicenter trial, we assessed whether intravenous immunoglobulin G (ivlgG) reduced 28-day mortality and improved morbidity in patients with score-defined severe sepsis. Design: Randomized, double-blind, placebo-controlled, multicenter trial. Setting: Twenty-three medical and surgical intensive care units in university centers and large teaching hospitals. Patients: Patients (n = 653) with score-defined sepsis (sepsis score 12-27) and score-defined sepsis-induced severity of disease (Acute Physiology and Chronic Health Evaluation II score 20-35). Interventions. Patients were assigned to receive either placebo or ivlgG (day 0, 0.6 g/kg body weight; day 1, 0.3 g/kg body weight). Measurements and Main Results. The prospectively defined primary end point was death from any cause after 28 days. Prospectively defined secondary end points were 7-day all-cause mortality, short-term change in morbidity, and pulmonary function at day 4. Six hundred fifty-three patients from 23 active centers formed the intention-to-treat group, 624 patients the per-protocol group (placebo group, n = 303; ivIgG group, n = 321). The 28-day mortality rate was 37.3% in the placebo group and 39.3% in the ivIgG group and thus not significantly different (p = .6695). Seven-day mortality was not reduced, and 4-day pulmonary function was not improved. Drug-related adverse events were rare in both groups. Exploratory findings revealed a 3-day shortening of mechanical ventilation in the surviving patients and no effect of ivIgG on plasma levels of interleukin-6 and tumor necrosis factor receptors I and II. Conclusions: In patients with score-defined severe sepsis, ivIgG with a total dose of 0.9 g/kg body weight does not reduce mortality.