Human recombinant activated protein C for severe sepsis

Abstract

This updated review found no evidence suggesting that APC should be used for treating patients with severe sepsis or septic shock. Additionally, APC is associated with a higher risk of bleeding. Unless additional RCTs provide evidence of a treatment effect, policy-makers, clinicians and academics should not promote the use of APC.

Adventure of Recombinant Human Activated Protein C in Sepsis and New Treatment Hopes on the Horizon

“…In The Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) study, rhAPC treatment was applied at a dose of 24 mcg/kg/h for 96-hour duration, to patients with mild to moderate sepsis. The authors demonstrated that rhAPC did not have any beneficial effect in patients with an APACHE 2 score of < 25 or in those with single organ failure; a report which was consistent with results of the PROWESS study [19]. Interestingly, both studies demonstrated that the 28-day mortality rate was higher in patients with single organ dysfunction and those who underwent surgery just prior to the administration of rhAPC [9].…”

“…As a result, there were found no evidence suggesting that rhAPC should be used for treating patients with severe sepsis or septic shock in this updated review [22]. In addition to that, rhAPC was associated with a higher risk of bleeding such as seen in many other studies [22,23]. At the end of this metanalysis, they concluded that unless additional Fig.…”

Adventure of Recombinant Human Activated Protein C in Sepsis and New Treatment Hopes on the Horizon

“…In The Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) study, rhAPC treatment was applied at a dose of 24 mcg/kg/h for 96-hour duration, to patients with mild to moderate sepsis. The authors demonstrated that rhAPC did not have any beneficial effect in patients with an APACHE 2 score of < 25 or in those with single organ failure; a report which was consistent with results of the PROWESS study [19]. Interestingly, both studies demonstrated that the 28-day mortality rate was higher in patients with single organ dysfunction and those who underwent surgery just prior to the administration of rhAPC [9].…”

“…As a result, there were found no evidence suggesting that rhAPC should be used for treating patients with severe sepsis or septic shock in this updated review [22]. In addition to that, rhAPC was associated with a higher risk of bleeding such as seen in many other studies [22,23]. At the end of this metanalysis, they concluded that unless additional Fig.…”

A Systematic Summary of Systematic Reviews on Anticoagulant Therapy in Sepsis

“…Study characteristics are summarized in Table 1. The target agent of 19 systematic reviews is as follows: antithrombin ( n = 4) [10,11,12,13], rTM ( n = 3) [9,14,15], heparin and low-molecular-weight heparin (LMWH) ( n = 3) [16,17,18], recombinant human activated protein C ( n = 8) [19,20,21,22,23,24,25,26], and all anticoagulants ( n = 1), which included all anticoagulant agents and evaluated separate meta-analyses in different populations [27].…”

An integrated transcriptome and expressed variant analysis of sepsis survival and death

“…This plasma protein, often depleted in severe sepsis, was the basis for recombinant activated protein C as the only drug approved for the treatment of severe sepsis. Subsequent trials failed to replicate the beneficial effects, prompting its removal from the market [ 39 ]. PROC expression was decreased to a similar degree in sepsis survivors and sepsis non-survivors when compared to SIRS.…”

Adventure of Recombinant Human Activated Protein C in Sepsis and New Treatment Hopes on the Horizon

“…In The Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) study, rhAPC treatment was applied at a dose of 24 mcg/kg/h for 96-hour duration, to patients with mild to moderate sepsis. The authors demonstrated that rhAPC did not have any beneficial effect in patients with an APACHE 2 score of < 25 or in those with single organ failure; a report which was consistent with results of the PROWESS study [19]. Interestingly, both studies demonstrated that the 28-day mortality rate was higher in patients with single organ dysfunction and those who underwent surgery just prior to the administration of rhAPC [9].…”

“…As a result, there were found no evidence suggesting that rhAPC should be used for treating patients with severe sepsis or septic shock in this updated review [22]. In addition to that, rhAPC was associated with a higher risk of bleeding such as seen in many other studies [22,23]. At the end of this metanalysis, they concluded that unless additional Fig.…”

A Systematic Summary of Systematic Reviews on Anticoagulant Therapy in Sepsis

“…Study characteristics are summarized in Table 1. The target agent of 19 systematic reviews is as follows: antithrombin ( n = 4) [10,11,12,13], rTM ( n = 3) [9,14,15], heparin and low-molecular-weight heparin (LMWH) ( n = 3) [16,17,18], recombinant human activated protein C ( n = 8) [19,20,21,22,23,24,25,26], and all anticoagulants ( n = 1), which included all anticoagulant agents and evaluated separate meta-analyses in different populations [27].…”

An integrated transcriptome and expressed variant analysis of sepsis survival and death

“…This plasma protein, often depleted in severe sepsis, was the basis for recombinant activated protein C as the only drug approved for the treatment of severe sepsis. Subsequent trials failed to replicate the beneficial effects, prompting its removal from the market [ 39 ]. PROC expression was decreased to a similar degree in sepsis survivors and sepsis non-survivors when compared to SIRS.…”

Adventure of Recombinant Human Activated Protein C in Sepsis and New Treatment Hopes on the Horizon

“…In The Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) study, rhAPC treatment was applied at a dose of 24 mcg/kg/h for 96-hour duration, to patients with mild to moderate sepsis. The authors demonstrated that rhAPC did not have any beneficial effect in patients with an APACHE 2 score of < 25 or in those with single organ failure; a report which was consistent with results of the PROWESS study [19]. Interestingly, both studies demonstrated that the 28-day mortality rate was higher in patients with single organ dysfunction and those who underwent surgery just prior to the administration of rhAPC [9].…”

“…As a result, there were found no evidence suggesting that rhAPC should be used for treating patients with severe sepsis or septic shock in this updated review [22]. In addition to that, rhAPC was associated with a higher risk of bleeding such as seen in many other studies [22,23]. At the end of this metanalysis, they concluded that unless additional Fig.…”

A Systematic Summary of Systematic Reviews on Anticoagulant Therapy in Sepsis

“…Study characteristics are summarized in Table 1. The target agent of 19 systematic reviews is as follows: antithrombin ( n = 4) [10,11,12,13], rTM ( n = 3) [9,14,15], heparin and low-molecular-weight heparin (LMWH) ( n = 3) [16,17,18], recombinant human activated protein C ( n = 8) [19,20,21,22,23,24,25,26], and all anticoagulants ( n = 1), which included all anticoagulant agents and evaluated separate meta-analyses in different populations [27].…”

An integrated transcriptome and expressed variant analysis of sepsis survival and death

“…This plasma protein, often depleted in severe sepsis, was the basis for recombinant activated protein C as the only drug approved for the treatment of severe sepsis. Subsequent trials failed to replicate the beneficial effects, prompting its removal from the market [ 39 ]. PROC expression was decreased to a similar degree in sepsis survivors and sepsis non-survivors when compared to SIRS.…”