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 (ivIgG) reduced 28-day mortality and improved morbidity in patients with score-defined severe sepsis.


METHODS
Randomized, double-blind, placebo-controlled, multicenter trial.


METHODS
Twenty-three medical and surgical intensive care units in university centers and large teaching hospitals.


METHODS
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).


METHODS
Patients were assigned to receive either placebo or ivIgG (day 0, 0.6 g/kg body weight; day 1, 0.3 g/kg body weight).


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.
Werdan
Karl
K
Department of Medicine III, University Hospital, Martin-Luther-University Halle-Wittenberg, Germany. karl.werdan@medizin.uni-halle.de
Pilz
Günter
G
Bujdoso
Oskar
O
Fraunberger
Peter
P
Neeser
Gertraud
G
Schmieder
Roland Erich
RE
Viell
Burkhard
B
Marget
Walter
W
Seewald
Margret
M
Walger
Peter
P
Stuttmann
Ralph
R
Speichermann
Norbert
N
Peckelsen
Claus
C
Kurowski
Volkhard
V
Osterhues
Hans-Heinrich
HH
Verner
Ljiljana
L
Neumann
Roswita
R
Müller-Werdan
Ursula
U
D018806:APACHE; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000276:immunology / Q000628:therapy*; D012772:Shock, Septic / Q000276:immunology / Q000628:therapy; D016019:Survival Analysis
D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors