Abstract
Demonstrating the efficacy of new treatments in any condition may be a challenging
endeavor, and is particularly the case in sepsis. In the early 21st century, recombinant
activated protein C showed a survival benefit in severe sepsis; however, subsequent
studies could not replicate these results, leading to the discontinuation of this
agent. Several potential reasons have been proposed for the unfavorable results of
trials, including choosing an inappropriate outcome target. Concerning anticoagulant
therapies, some studies have targeted sepsis with disseminated intravascular coagulation
(DIC) and demonstrated clinical benefits, while other studies have focused on severe
sepsis or septic shock independent of whether patients had DIC. The timing for treatment
initiation, dosage, and duration of anticoagulant agents could be significant factors
contributing to the limitations faced in these trials. Moreover, relying solely on
28-day mortality as the primary endpoint for sepsis trials may not be appropriate,
as it can be influenced by various factors beyond anticoagulant therapies, and discernment
in a shorter period might be more pertinent. Success in clinical trials is more likely
if these issues are addressed and improvements are made. Recent clinical trials concentrating
on anticoagulants are increasingly targeting sepsis or septic shock with coagulopathy,
and adopting composite endpoints, including DIC resolution, is anticipated to overcome
some of these challenges.
Keywords sepsis - disseminated intravascular coagulation - clinical trial - anticoagulants
- composite endpoint
