Eritoran May Reduce Mortality in Patients With High-Risk Severe Sepsis: Presented at SCCM
By Sophie Bainbridge
SAN DIEGO -- January 21, 2011 -- In patients with high-risk severe sepsis, the investigational drug eritoran, a toll-like receptor 4 antagonist, appeared to reduce 28-day mortality compared with placebo, researchers said here at the Society of Critical Care Medicine (SCCM) 40th Critical Care Congress.
Gary T. Kinasewitz, MD, Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, presented data from a randomised, placebo-controlled phase 2 trial which evaluated the efficacy of eritoran in 98 patients aged 18 to 85 years with severe sepsis.
The purpose of this research was to determine if 28-day all-cause mortality in high-risk severe sepsis patients receiving eritoran was affected by concomitant use of drotrecogin alfa, a recombinant form of human activated protein C that has antithrombotic, anti-inflammatory, and profibrinolytic properties.
"We expected that administration of concomitant drotrecogin would result in an additional reduction in mortality," Dr. Kinasewitz explained on January 18.
In the study, patients with baseline Acute Physiology and Chronic Health Evaluation II (APACHE II) scores >=25 received eritoran tetrasodium 105 mg, and 51 patients received placebo.
Twelve (34%) of the 35 eritoran-treated patients who were not receiving concomitant drotrecogin alfa died, and 20 (50%) of the 40 placebo-treated patients who were not receiving drotrecogin alfa died.
Among the 12 patients who were receiving concomitant drotrecogin alfa and eritoran, 5 (42%) died, and of the 11 placebo-treated patients receiving drotrecogin alfa, 5 (45%) died.
The study found that overall, there was better survival in eritoran-treated patients -- 30 of 47 patients (64%) survived compared with 26 of 51 (51%) of placebo-treated patients.
The incidence of serious adverse events was similar in the eritoran and placebo arms. Also, while there were differences in the incidence of thrombotic and bleeding complications between the patients who did and did not get drotrecogin alfa, they were not statistically significant, Dr. Kinasewitz said.
"Outcomes were similar regardless of whether or not drotrecogin alfa was used and the P value was 0.6075," he noted.
Finally, the relative risk of all-cause mortality for eritoran compared with placebo was 0.74 when stratified by concomitant drotrecogin alfa use.
"In this study eritoran appeared to reduce 28-day mortality over that seen with placebo, and the addition of drotrecogin alfa did not appear to reduce this mortality further," Dr. Kinasewitz said. "However, this apparent lack of effect may be explained by the small sample size."
[Presentation title: 28-Day Mortality in High-Risk Patients With Severe Sepsis Receiving Eritoran With or Without Drotrecogin Alfa: Analysis of Data From a Phase II Trial. Abstract 90]
By Sophie Bainbridge
SAN DIEGO -- January 21, 2011 -- In patients with high-risk severe sepsis, the investigational drug eritoran, a toll-like receptor 4 antagonist, appeared to reduce 28-day mortality compared with placebo, researchers said here at the Society of Critical Care Medicine (SCCM) 40th Critical Care Congress.
Gary T. Kinasewitz, MD, Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, presented data from a randomised, placebo-controlled phase 2 trial which evaluated the efficacy of eritoran in 98 patients aged 18 to 85 years with severe sepsis.
The purpose of this research was to determine if 28-day all-cause mortality in high-risk severe sepsis patients receiving eritoran was affected by concomitant use of drotrecogin alfa, a recombinant form of human activated protein C that has antithrombotic, anti-inflammatory, and profibrinolytic properties.
"We expected that administration of concomitant drotrecogin would result in an additional reduction in mortality," Dr. Kinasewitz explained on January 18.
In the study, patients with baseline Acute Physiology and Chronic Health Evaluation II (APACHE II) scores >=25 received eritoran tetrasodium 105 mg, and 51 patients received placebo.
Twelve (34%) of the 35 eritoran-treated patients who were not receiving concomitant drotrecogin alfa died, and 20 (50%) of the 40 placebo-treated patients who were not receiving drotrecogin alfa died.
Among the 12 patients who were receiving concomitant drotrecogin alfa and eritoran, 5 (42%) died, and of the 11 placebo-treated patients receiving drotrecogin alfa, 5 (45%) died.
The study found that overall, there was better survival in eritoran-treated patients -- 30 of 47 patients (64%) survived compared with 26 of 51 (51%) of placebo-treated patients.
The incidence of serious adverse events was similar in the eritoran and placebo arms. Also, while there were differences in the incidence of thrombotic and bleeding complications between the patients who did and did not get drotrecogin alfa, they were not statistically significant, Dr. Kinasewitz said.
"Outcomes were similar regardless of whether or not drotrecogin alfa was used and the P value was 0.6075," he noted.
Finally, the relative risk of all-cause mortality for eritoran compared with placebo was 0.74 when stratified by concomitant drotrecogin alfa use.
"In this study eritoran appeared to reduce 28-day mortality over that seen with placebo, and the addition of drotrecogin alfa did not appear to reduce this mortality further," Dr. Kinasewitz said. "However, this apparent lack of effect may be explained by the small sample size."
[Presentation title: 28-Day Mortality in High-Risk Patients With Severe Sepsis Receiving Eritoran With or Without Drotrecogin Alfa: Analysis of Data From a Phase II Trial. Abstract 90]