Mortality reduction by talactoferrin alfa (TLF) in severe sepsis with different types of infections.

Abstract

9024 Background: This randomized, placebo-controlled, double-blind study evaluated TLF, an oral agent with immunomodulatory and antibacterial properties, on 28-d all-cause mortality in patients with severe sepsis. TLF previously showed activity in NSCLC as monotherapy in the 2nd/3rd line setting and when added to a 1st line chemotherapy doublet. Methods: Eligible pts had onset of severe sepsis (at least 1 organ dysfunction) within 24 hours prior to randomization to TLF 1.5 g or placebo enterally (oral or by feeding tube) q 8 h for a maximum of 28 d in addition to standard care including drotrecogin alfa (activated). Results: Baseline characteristics of 190 randomized pts (97 TLF; 93 placebo [P]) were similar. The study met the primary endpoint of reducing 28-d mortality in the modified ITT population (14.4% TLF/26.6% P; 2-tailed P = 0.052 [Guntupalli ATS 2010]). The most common sites of infection were lung (46% TLF/52% P) and urinary tract (21% TLF/23% P). A positive culture was obtained in 66% TLF/71% P pts. Of the positive cultures, Gram + isolates were the most common (73% TLF/79% P) followed by Gram - (36% TLF/44% P) and fungal (16% TLF, 6% P). Of the positive cultures, blood was the most common site for isolation (59% TLF/49% P). Polymicrobial infection was present in 28% TLF/34% P pts. There was a consistent mortality decrease in the TLF arm by sites of infection (lung: 18% TLF/38% P p=0.04; urinary tract 5% TLF/29% P p=0.09), with the exception of intra-abdominal infection (31% TLF/14% P p=0.38). A consistent reduction in mortality also occurred in pts with a single isolate (19% TLF/29% P) and polymicrobial isolates (15% TLF/22% P). For single isolates, mortality was lower for Gram + (22% TLF/32% P) and Gram – (18% TLF/33% P) infections. Conclusions: The effect of TLF on mortality reduction appears consistent across different sites and types of infections. Further study of TLF in severe sepsis is warranted.