Heparin anticoagulation to improve outcomes in septic shock: The HALO International Phase II Trial

Life-threatening infections account for 10% of all intensive care unit admissions and constitute the second more frequent cause of death in the ICU after heart diseases. The most common cause of death in patients admitted with life-threatening infections is multi-organ failure that is mediated by severe inflammation. Given the relationship between inflammation and blood clotting, blood-thinners (also called anticoagulants) have been used to decrease inflammation and the formation of small clots, and to increase survival. Several lines of evidence suggest that heparin, a widely available and inexpensive blood-thinner, may improve survival in patients diagnosed with life-threatening infection. Prior to conducting a large and costly international trial, we propose a smaller trial to demonstrate that heparin works to improve important clinical endpoints. We will enroll 500 patients from approximately 20 intensive care units in 4 countries. The primary objective of this study is to demonstrate that unfractionated heparin can safely reduce the number of days a patient requires life support. Patients with life threatening infections will have an equal chance of receiving an intravenous infusion of heparin at 18 units/kg or whatever is typically given to prevent blood clots in the ICU. The results of our trial will allow us to decide if a large international trial designed to answer the question "Does heparin reduce mortality in septic shock?" is justified. If justified, this small trial will help us to estimate an initial sample size and number of centres needed to execute the phase III trial.