"CAP remains the most common cause of death from infection," Dr. Wunderink said. "Anti-clotting therapies are sought to complement the antimicrobial treatment and supportive care measures that are currently used for sCAP patients."
In this study, researchers enrolled 2,138 sCAPpatients from 188 centers from 2005 to 2008, randomizing them to receive tifacogin or placebo intravenously for four days. Although two doses of tifacogin (0.025 mg/kg/h and 0.075 mg/kg/h) were initially included in the study, the higher dose was dropped early on when no benefit was demonstrated.
At the end of the study although tifacogin did show an effect on clotting measures in the blood, the researchers found mortality rates and the incidence of adverse events were similar in both the tifacogin and placebo groups.
Dr. Wunderink said the study's negative results could be due to several factors.
"The coagulation and inflammatory responses may have been irreversibly activated before tifacogin was administered, or specific processes that occur during CAP may have blunted the effect of the drug," he said. "However, the most logical explanation is that tissue factor activation, while important, may not be a critical step in the pathogenesis of sCAP mortality."
Although the study showed no benefit associated with the use of tifacogin in sCAP patients, Dr. Wunderink said it clearly demonstrates the need for additional research to improve sCAP mortality rates.
"CAPTIVATE represents the largest clinical trial of severe CAP performed to date," Dr. Wunderink said. "The design and execution of the study demonstrates that a more homogeneous population with a single source ofinfection, rather than a more generic sepsis population, can be defined, which will be of benefit for future studies.
"Although theprimary end-point was not achieved, this study d
|Contact: Brian Kell|
American Thoracic Society