Safety of Heparin in Patients With Septic Shock

Sponsor

University of Colorado, Denver (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01234285

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Sepsis	Drug: heparin Drug: heparin Drug: heparin Drug: heparin	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2010

Anticipated Primary Completion Date :

Apr 1, 2013

Anticipated Study Completion Date :

Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: intravenous heparin aPTT 40-50 seconds Patients 11-15: IV heparin, target aPTT range 40-50 seconds	Drug: heparin 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.
Experimental: intravenous heparin Patients 26-40: IV heparin, target range aPTT 50-60 seconds	Drug: heparin 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. Drug: heparin 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.
Experimental: Intravenous heparin Patients 41-55 IV heparin, target aPTT range 60-70 seconds	Drug: heparin 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. Drug: heparin 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.
Active Comparator: sq heparin three times a day Patients 1-10 will receive subcutaneous heparin three times a day	Drug: heparin 5000 units subcutaneously three times a day, starting within 24 hours of ICU admission up to 6 days.

Outcome Measures

Primary Outcome Measures

Incidence of major bleeding [This outcome will be measured for an average of 30 days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 -