Abstract
Background. A recombinant, soluble fusion protein that is a dimer of an extracellular portion of the human tumor necrosis factor (TNF) receptor and the Fc portion of IgG1 (TNFR:Fc) binds and neutralizes TNF-α and prevents death in animal models of bacteremia and endotoxemia. Methods. To evaluate the safety and efficacy of TNFR:Fc in the treatment of septic shock, we conducted a randomized, double-blind, placebo-controlled, multicenter trial. A total of 141 patients were randomly assigned to receive either placebo or a single intravenous infusion of one of three doses of TNFR:Fc (0.15, 0.45, or 1.5 mg per kilogram of body weight). The primary end point was mortality from all causes at 28 days. Results. There were 10 deaths among the 33 patients in the placebo group (30 percent mortality), 9 deaths among the 30 patients receiving the low dose of TNFR:Fc (30 percent mortality), 14 deaths among the 29 receiving the middle dose (48 percent mortality), and 26 deaths among the 49 receiving the high dose (53 percent mortality) (P=0.02 for the dose- response relation). Baseline differences in the severity of illness did not account for the increased mortality in the groups receiving the higher doses of TNFR:Fc. Conclusions. In patients with septic shock, treatment with the TNFR:Fc fusion protein does not reduce mortality, and higher doses appear to be associated with increased mortality.
| Original language | English |
|---|---|
| Pages (from-to) | 1697-1702 |
| Number of pages | 6 |
| Journal | New England Journal of Medicine |
| Volume | 334 |
| Issue number | 26 |
| DOIs | |
| State | Published - Jun 27 1996 |
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ASJC Scopus subject areas
- Medicine(all)
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Treatment of septic shock with the tumor necrosis factor receptor : Fc fusion protein. / Fisher, Charles J.; Agosti, Jan M.; Opal, Steven M.; Lowry, Stephen F.; Balk, Robert A.; Sadoff, Jerald C.; Abraham, Edward; Schein, Roland; Benjamin, Ernest.
In: New England Journal of Medicine, Vol. 334, No. 26, 27.06.1996, p. 1697-1702.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Treatment of septic shock with the tumor necrosis factor receptor
T2 - Fc fusion protein
AU - Fisher, Charles J.
AU - Agosti, Jan M.
AU - Opal, Steven M.
AU - Lowry, Stephen F.
AU - Balk, Robert A.
AU - Sadoff, Jerald C.
AU - Abraham, Edward
AU - Schein, Roland
AU - Benjamin, Ernest
PY - 1996/6/27
Y1 - 1996/6/27
N2 - Background. A recombinant, soluble fusion protein that is a dimer of an extracellular portion of the human tumor necrosis factor (TNF) receptor and the Fc portion of IgG1 (TNFR:Fc) binds and neutralizes TNF-α and prevents death in animal models of bacteremia and endotoxemia. Methods. To evaluate the safety and efficacy of TNFR:Fc in the treatment of septic shock, we conducted a randomized, double-blind, placebo-controlled, multicenter trial. A total of 141 patients were randomly assigned to receive either placebo or a single intravenous infusion of one of three doses of TNFR:Fc (0.15, 0.45, or 1.5 mg per kilogram of body weight). The primary end point was mortality from all causes at 28 days. Results. There were 10 deaths among the 33 patients in the placebo group (30 percent mortality), 9 deaths among the 30 patients receiving the low dose of TNFR:Fc (30 percent mortality), 14 deaths among the 29 receiving the middle dose (48 percent mortality), and 26 deaths among the 49 receiving the high dose (53 percent mortality) (P=0.02 for the dose- response relation). Baseline differences in the severity of illness did not account for the increased mortality in the groups receiving the higher doses of TNFR:Fc. Conclusions. In patients with septic shock, treatment with the TNFR:Fc fusion protein does not reduce mortality, and higher doses appear to be associated with increased mortality.
AB - Background. A recombinant, soluble fusion protein that is a dimer of an extracellular portion of the human tumor necrosis factor (TNF) receptor and the Fc portion of IgG1 (TNFR:Fc) binds and neutralizes TNF-α and prevents death in animal models of bacteremia and endotoxemia. Methods. To evaluate the safety and efficacy of TNFR:Fc in the treatment of septic shock, we conducted a randomized, double-blind, placebo-controlled, multicenter trial. A total of 141 patients were randomly assigned to receive either placebo or a single intravenous infusion of one of three doses of TNFR:Fc (0.15, 0.45, or 1.5 mg per kilogram of body weight). The primary end point was mortality from all causes at 28 days. Results. There were 10 deaths among the 33 patients in the placebo group (30 percent mortality), 9 deaths among the 30 patients receiving the low dose of TNFR:Fc (30 percent mortality), 14 deaths among the 29 receiving the middle dose (48 percent mortality), and 26 deaths among the 49 receiving the high dose (53 percent mortality) (P=0.02 for the dose- response relation). Baseline differences in the severity of illness did not account for the increased mortality in the groups receiving the higher doses of TNFR:Fc. Conclusions. In patients with septic shock, treatment with the TNFR:Fc fusion protein does not reduce mortality, and higher doses appear to be associated with increased mortality.
UR - http://www.scopus.com/inward/record.url?scp=0029900294&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029900294&partnerID=8YFLogxK
U2 - 10.1056/NEJM199606273342603
DO - 10.1056/NEJM199606273342603
M3 - Article
C2 - 8637514
AN - SCOPUS:0029900294
VL - 334
SP - 1697
EP - 1702
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 26
ER -