Unfractioned Heparin for Treatment of Sepsis
The purpose of this study is to determine whether low dose continuous infusion of unfractioned heparin (500 units/hour), in addition to the standard treatment, is efficacious as complementary therapy for sepsis patients.
Drug: Unfractioned heparin
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Unfractioned Heparin for Treatment of Sepsis: A Randomized Clinical Trial (The HETRASE Study)|
- Change from baseline Multiple Organ Dysfunction (MOD) score [ Time Frame: 15 days ] [ Designated as safety issue: No ]
- Length of stay [ Time Frame: During hospitalization ] [ Designated as safety issue: No ]
- 28-day all-cause mortality [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2005|
|Study Completion Date:||July 2007|
|Primary Completion Date:||July 2007 (Final data collection date for primary outcome measure)|
Standard treatment plus unfractioned heparin low-dose continuous infusion
Drug: Unfractioned heparin
Low-dose continuous-infusion, 500 units/hour per seven days
Placebo Comparator: 2
Standard treatment plus placebo
Sepsis is considered a leading cause of death worldwide with approximately 18 million cases annually and a mortality rate of almost 30%. The search for efficacious therapeutic approaches has largely failed and only a few of the recent interventions, such as activated protein C and low dose steroids, have shown some success in improving survival. However, these interventions were tested only in patients with severe sepsis and/or septic shock and although these groups exhibit the highest mortality, they represent less than 50% of the total affected population. Furthermore, these interventions necessitate special devices, tests and/or drugs that might be unavailable or simply unaffordable in resource-limited settings.
Animal and human models have suggested that heparin, in addition to successfully inhibiting the coagulation cascade, may also modulate the wide array of responses to infection. Furthermore, the three clinical trials for recombinant anticoagulants allowed the use of prophylactic treatment for venous thrombosis with a dose of unfractioned heparin (UFH) of up to 10,000 or 15,000 units subcutaneously per day. When those who did receive heparin were compared to those who did not in the placebo arms of the clinical trials, all three studies showed a higher mortality in the subgroups that did not receive heparin. Although this is not a randomized comparison, a constant result in three different study populations with variable entry criteria, along with the natural heterogeneity of the illness, strongly fosters the hypothesis that heparin might reduce, beyond its known anticoagulant and antithrombotic properties, the overall mortality for sepsis.
In this project, we propose a phase II/III, randomized, double-masked, placebo-controlled, single-center clinical trial with a total sample size of 310 patients, for testing low dose continuous infusions of UFH (500 units/hour) for 7 days, as complementary treatment for septic patients. Our primary aims are to estimate the effects of UFH on length of stay and change from baseline Multiple Organic Dysfunction (MOD) score. Secondary objectives are to estimate the effects of UFH on 28-day all-cause mortality, and to estimate the possible effect-modification on 28-day all-cause mortality, in subgroups defined by site of infection and baseline values of APACHE II score, MOD score and D-dimer.
|Hospital Universitario San Vicente de Paul|
|Medellin, Antioquia, Colombia|
|Principal Investigator:||Fabián A Jaimes, MD, MSc, PhD||Universidad de Antioquia|