|Reference : Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragm...|
|Scientific journals : Article|
|Human health sciences : Anesthesia & intensive care|
|Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis: The RAMSES Study|
|Reinhart, Konrad [ > > ]|
|Menges, Thilo [ > > ]|
|Gardlund, Bengt [ > > ]|
|Zwaveling, Jan Harm [ > > ]|
|Smithes, Mark [ > > ]|
|Vincent, Jean-Louis [ > > ]|
|Tellado, Jose Maria [ > > ]|
|Salgado-Remigio, Antonio [ > > ]|
|Zimlichman, Reuven [ > > ]|
|Withington, Stuart [ > > ]|
|Tschaikowsky, Klaus [ > > ]|
|Brase, Rainer [ > > ]|
|Damas, Pierre [Université de Liège - ULg > > Soins intensifs >]|
|Kupper, Hartmut [ > > ]|
|Kempeni, Joachim [ > > ]|
|Eiselstein, Juergen [ > > ]|
|Kaul, Martin [ > > ]|
|Critical Care Medicine|
|Lippincott Williams & Wilkins|
|Yes (verified by ORBi)|
|[en] sepsis ; interleukin-6 ; tumor necrosis factor ; monoclonal antibody ; cytokines ; infection ; critical illness ; clinical trial ; septic shock|
|[en] Objective: This study investigated whether treatment with the
anti-tumor necrosis factor-a 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
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 5 224) or placebo (n 5 222).
Patients with a negative IL-6 test (n 5 498) 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
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.
|Researchers ; Professionals|
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