OBJECTIVE: This study investigated whether treatment with the anti-tumor necrosis factor-alpha monoclonal antibody afelimomab would improve survival in septic patients with serum interleukin (IL)-6 concentrations of >1000 pg/mL. DESIGN: Multicenter, double-blind, randomized, placebo-controlled study. SETTING:Eighty-four intensive care units in academic medical centers in Europe and Israel. PATIENTS: A total of 944 septic patients were screened and stratified by the results of a rapid qualitative immunostrip test for serum IL-6 concentrations. Patients with a positive test kit result indicating IL-6 concentrations of >1000 pg/mL were randomized to receive either afelimomab (n = 224) or placebo (n = 222). Patients with a negative IL-6 test (n = 498) were not randomized and were followed up for 28 days. INTERVENTIONS: Treatment consisted of 15-min infusions of 1 mg/kg afelimomab or matching placebo every 8 hrs for 3 days. Standard surgical and intensive care therapy was otherwise delivered. MEASUREMENTS AND MAIN RESULTS: The study was terminated prematurely after an interim analysis estimated that the primary efficacy end points would not be met. The 28-day mortality rate in the nonrandomized patients (39.6%, 197 of 498) was significantly lower (p <.001) than that found in the randomized patients (55.8%, 249 of 446). The mortality rates in the IL-6 test kit positive patients randomized to afelimomab and placebo were similar, 54.0% (121 of 224) vs. 57.7% (128 of 222), respectively. Treatment with afelimomab was not associated with any particular adverse events. CONCLUSIONS: The IL-6 immunostrip test identified two distinct sepsis populations with significantly different mortality rates. A small (3.7%) absolute reduction in mortality rate was found in the afelimomab-treated patients. The treatment difference did not reach statistical significance.
RCT Entities:
OBJECTIVE: This study investigated whether treatment with the anti-tumor necrosis factor-alpha monoclonal antibody afelimomab would improve survival in septic patients with serum interleukin (IL)-6 concentrations of >1000 pg/mL. DESIGN: Multicenter, double-blind, randomized, placebo-controlled study. SETTING: Eighty-four intensive care units in academic medical centers in Europe and Israel. PATIENTS: A total of 944 septic patients were screened and stratified by the results of a rapid qualitative immunostrip test for serum IL-6 concentrations. Patients with a positive test kit result indicating IL-6 concentrations of >1000 pg/mL were randomized to receive either afelimomab (n = 224) or placebo (n = 222). Patients with a negative IL-6 test (n = 498) were not randomized and were followed up for 28 days. INTERVENTIONS: Treatment consisted of 15-min infusions of 1 mg/kg afelimomab or matching placebo every 8 hrs for 3 days. Standard surgical and intensive care therapy was otherwise delivered. MEASUREMENTS AND MAIN RESULTS: The study was terminated prematurely after an interim analysis estimated that the primary efficacy end points would not be met. The 28-day mortality rate in the nonrandomized patients (39.6%, 197 of 498) was significantly lower (p <.001) than that found in the randomized patients (55.8%, 249 of 446). The mortality rates in the IL-6 test kit positive patients randomized to afelimomab and placebo were similar, 54.0% (121 of 224) vs. 57.7% (128 of 222), respectively. Treatment with afelimomab was not associated with any particular adverse events. CONCLUSIONS: The IL-6 immunostrip test identified two distinct sepsis populations with significantly different mortality rates. A small (3.7%) absolute reduction in mortality rate was found in the afelimomab-treated patients. The treatment difference did not reach statistical significance.
Authors: Yoram Vodovotz; Gregory Constantine; James Faeder; Qi Mi; Jonathan Rubin; John Bartels; Joydeep Sarkar; Robert H Squires; David O Okonkwo; Jörg Gerlach; Ruben Zamora; Shirley Luckhart; Bard Ermentrout; Gary An Journal: Immunopharmacol Immunotoxicol Date: 2010-06 Impact factor: 2.730
Authors: Anders Perner; Anthony C Gordon; Derek C Angus; Francois Lamontagne; Flavia Machado; James A Russell; Jean-Francois Timsit; John C Marshall; John Myburgh; Manu Shankar-Hari; Mervyn Singer Journal: Intensive Care Med Date: 2017-05-12 Impact factor: 17.440
Authors: Kevin W McConnell; Jonathan E McDunn; Andrew T Clark; W Michael Dunne; David J Dixon; Isaiah R Turnbull; Peter J Dipasco; William F Osberghaus; Benjamin Sherman; James R Martin; Michael J Walter; J Perren Cobb; Timothy G Buchman; Richard S Hotchkiss; Craig M Coopersmith Journal: Crit Care Med Date: 2010-01 Impact factor: 7.598
Authors: Hector R Wong; Natalie Cvijanovich; Richard Lin; Geoffrey L Allen; Neal J Thomas; Douglas F Willson; Robert J Freishtat; Nick Anas; Keith Meyer; Paul A Checchia; Marie Monaco; Kelli Odom; Thomas P Shanley Journal: BMC Med Date: 2009-07-22 Impact factor: 8.775