Safety of Heparin in Patients With Septic Shock

Study Overview
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Brief Summary
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Sepsis is a syndrome comprised of a systemic inflammatory response, signs of tissue hypoperfusion, and organ in the setting of presumed infection. Heparin, in addition to being an anticoagulant, is also a well-known antiinflammatory. The investigators believe that unfractionated heparin has the potential to save the lives of septic patients at a drastically reduced cost. This is a dose escalation study to determine the safety of increasing levels of heparin in this patient population; compare markers of anticoagulation and inflammation between treatment groups; and compare clinical outcomes between groups.

Official Title
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Safety of Heparin Anticoagulation for Prevention of Death in Patients With Septic Shock.

Conditions
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Sepsis

Intervention / Treatment
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* Drug: heparin
* Drug: heparin
* Drug: heparin
* Drug: heparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-90 in the medical or surgical intensive care unit Within 24 hours of diagnosis with sepsis as defined by the Bone criteria (see Appendix A); Acute Physiology and Chronic Health Evaluation (APACHE II) score of > 25; Signed consent Exclusion Criteria: Currently therapeutically anticoagulated for known thrombotic diagnosis (myocardial infarction, venous thromboembolism) known molecular hypercoagulable state (Factor V Leiden, lupus anticoagulant, antiphospholipid antibody syndrome); or use of cardiopulmonary support machines (left-ventricular assist device, intra-aortic balloon pump, veno-venous ultrafiltration, or extracorporeal membrane oxygenation. History of gastrointestinal or cerebral hemorrhage within past 3 months; Active bleeding; Known allergy or sensitivity to heparin; History of heparin-induced thrombocytopenia Organ transplantation recipient -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intravenous heparin aPTT 40-50 seconds<br>Patients 11-15: IV heparin, target aPTT range 40-50 seconds | Drug: heparin<br>* intravenous heparin titrated to an aPTT of 40-50 seconds starting between 300-500 units per hour and adjusted every 6 hours based on aPTT, starting within 24 hours of ICU admission up to 6 days.<br>|
| Experimental: intravenous heparin<br>Patients 26-40: IV heparin, target range aPTT 50-60 seconds | Drug: heparin<br>* intravenous heparin titrated to an aPTT of 50-60 seconds starting between 300-500 units per hour and adjusted every 6 hours based on aPTT, starting within 24 hours of ICU admission up to 6 days.<br>Drug: heparin<br>* intravenous heparin titrated to an aPTT of 40-45 seconds starting between 300-500 units per hour and adjusted every 6 hours based on aPTT, starting within 24 hours of ICU admission up to 6 days.<br>|
| Experimental: Intravenous heparin<br>Patients 41-55 IV heparin, target aPTT range 60-70 seconds | Drug: heparin<br>* intravenous heparin titrated to an aPTT of 50-60 seconds starting between 300-500 units per hour and adjusted every 6 hours based on aPTT, starting within 24 hours of ICU admission up to 6 days.<br>Drug: heparin<br>* intravenous heparin titrated to an aPTT of 40-45 seconds starting between 300-500 units per hour and adjusted every 6 hours based on aPTT, starting within 24 hours of ICU admission up to 6 days.<br>|
| Active Comparator: sq heparin three times a day<br>Patients 1-10 will receive subcutaneous heparin three times a day | Drug: heparin<br>* 5000 units subcutaneously three times a day, starting within 24 hours of ICU admission up to 6 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of major bleeding | Defined as:decrease in hemoglobin greater than 2g/dl and/or transfusion of 2 or more units of packed red blood cells. However, if there are obvious other reasons for bleeding, such as within 12 hours of major surgery, coagulopathy unrelated to heparin or an anatomical basis. | This outcome will be measured for an average of 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sepsis, septic shock, anticoagulation, intensive care unit