Skip to main content

Advertisement

Table 3 Safety assessment

From: Lack of evidence for qualitative treatment by disease severity interactions in clinical studies of severe sepsis

Study: agent Safety assessment
Opal et al. (2004) [28]: No differences between treatment groups in incidence of infectious events or serious bleeding events. No anti-PAFase antibody formation observed
Abraham et al. (2003) [29]: TFPI Increased incidence of bleeding complications in TFPI treatment group (serious adverse events with bleeding 6.5% with TFPI versus 4.8% with placebo for INR ≥ 1.2; 6.0% TFPI versus 3.3% placebo for INR <1.2)
Warren et al. (2001) [35]: ATIII Increased incidence of bleeding complications in ATIII treatment group (major bleeding 10.0% for ATIII versus 5.7% for placebo). No difference in event rates for other types of adverse events
Bernard et al. 1997 [44]: Ibuprofen No adverse findings noted. Second episodes of sepsis occurred more often in placebo group (8.2% versus 11.1% of patients)
Fisher et al. (1994) [32]; Knaus et al. (1996) [6]: IL-1ra (1st study) Cardiopulmonary arrest observed more often in IL-1ra treatment group (11% versus 8% of placebo patients)
Opal et al. (1997) [34]: IL-1ra (2nd study) No evidence of allergic reaction. No unique clinical or laboratory adverse events were significantly more frequent in IL-1ra treatment group
Greenman et al. (1991) [30]: E5 Evidence of an allergic reaction noted in one study. No unique clinical or laboratory adverse events were significantly more frequent in E5 treatment group. Positive IgG anti-murine antibody response developed in 47% of E5-treated patients
Abraham et al. (2001) [33]: Lenercept No unique clinical or laboratory adverse events were significantly more frequent in IL-1ra treatment group. Frequency of adverse events related to intracellular pathogen infection was similar between treatment groups
Reinhart et al. (2001) [46]: MAK 195F No unique clinical or laboratory adverse events were significantly more frequent in MAK 195F treatment group. IgG human antimouse antibodies developed in 16% of MAK 195F-treated patients. No evidence of allergic reactions
Abraham et al. (1998) [36]: BAYx1351 Human antimouse antibody titers positive in 59.7% of patients in the BAYx1351 treatment group. The rate of bacterial superinfections or recovery from superinfections did not differ between groups. Serum sickness reported in 0.5% and 0.1% of BAYx1351-treated and placebo-treated patients, respectively
Cohen and Carlet (1996) [47]: BAYx1351 Approximately 90% of BAYx1351-treated patients developed human anti-mouse antibodies
Abraham et al. (1995) [31]: BAYx1351 Serum sickness reported in 2.3% and 0.0% of BAYx1351-treated and placebo-treated patients, respectively. No differences in bacterial superinfections or recovery from superinfections were noted among treatment arms. Approximately 86% of BAYx1351-treated patients developed human antimouse antibodies
Bernard et al. (2001) [26]: rhAPC Increased incidence of bleeding complications in rhAPC treatment group (serious bleeding 3.5% for rhAPC versus 2.0% for placebo). No difference between treatment groups in the incidence of new infections. Neutralizing antibodies to APC not detected
Dhainaut et al. (1998) [48]: PAFra No difference in the incidence of adverse events between treatment groups
Albertson et al. (2003) [49]: MAB-T88 Hypotension and rash noted in three MAB-T88-treated patients. Higher number of adverse events reported in MAB-T88 treatment group than in the placebo group
Lopez et al. (2004) [50]: NOS inhibitor The number of patients experiencing an adverse event possibly related to study drug was higher in the 546C88 treatment group than in the placebo group (19% versus 8%). The majority of these adverse events involved the cardiovascular system (e.g. pulmonary hypertension, cardiac failure, cardiac arrest)
Panacek et al. (2004) [37]: afelimomab Human antimouse antibody formation rate was 23.6% in the afelimomab group and 6.3% in the control group. No clinical sequelae were associated with antibody formation
  1. ATIII, antithrombin III; IL-1ra, IL-1 receptor antagonist; INR, international normalized ratio; NOS, nitric oxide synthase; PAFra, platelet activating factor receptor antagonist; rhAPC, recombinant human activated protein C; TFPI, tissue factor pathway inhibitor.