Safety of Heparin in Patients With Septic Shock
Primary Purpose
Sepsis
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
heparin
heparin
heparin
heparin
Sponsored by
About this trial
This is an interventional treatment trial for Sepsis focused on measuring sepsis, septic shock, anticoagulation, intensive care unit
Eligibility Criteria
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 -
Sites / Locations
- University of Colorado Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
intravenous heparin aPTT 40-50 seconds
intravenous heparin
Intravenous heparin
sq heparin three times a day
Arm Description
Patients 11-15: IV heparin, target aPTT range 40-50 seconds
Patients 26-40: IV heparin, target range aPTT 50-60 seconds
Patients 41-55 IV heparin, target aPTT range 60-70 seconds
Patients 1-10 will receive subcutaneous heparin three times a day
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01234285
First Posted
September 23, 2010
Last Updated
May 19, 2014
Sponsor
University of Colorado, Denver
1. Study Identification
Unique Protocol Identification Number
NCT01234285
Brief Title
Safety of Heparin in Patients With Septic Shock
Official Title
Safety of Heparin Anticoagulation for Prevention of Death in Patients With Septic Shock.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2014
Overall Recruitment Status
Withdrawn
Why Stopped
Sara Cheng, MD has left the Univ. of Colorado and the study has been closed.
Study Start Date
December 2010 (undefined)
Primary Completion Date
April 2013 (Anticipated)
Study Completion Date
October 2013 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
4. Oversight
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis
Keywords
sepsis, septic shock, anticoagulation, intensive care unit
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
intravenous heparin aPTT 40-50 seconds
Arm Type
Experimental
Arm Description
Patients 11-15: IV heparin, target aPTT range 40-50 seconds
Arm Title
intravenous heparin
Arm Type
Experimental
Arm Description
Patients 26-40: IV heparin, target range aPTT 50-60 seconds
Arm Title
Intravenous heparin
Arm Type
Experimental
Arm Description
Patients 41-55 IV heparin, target aPTT range 60-70 seconds
Arm Title
sq heparin three times a day
Arm Type
Active Comparator
Arm Description
Patients 1-10 will receive subcutaneous heparin three times a day
Intervention Type
Drug
Intervention Name(s)
heparin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
heparin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
heparin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
heparin
Intervention Description
5000 units subcutaneously three times a day, starting within 24 hours of ICU admission up to 6 days.
Primary Outcome Measure Information:
Title
Incidence of major bleeding
Description
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.
Time Frame
This outcome will be measured for an average of 30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sara Cheng, MD;PhD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
11445742
Citation
Marshall JC. Inflammation, coagulopathy, and the pathogenesis of multiple organ dysfunction syndrome. Crit Care Med. 2001 Jul;29(7 Suppl):S99-106. doi: 10.1097/00003246-200107001-00032.
Results Reference
background
PubMed Identifier
16007415
Citation
Agarwal R, Gupta D. Anticoagulation in sepsis: is low-dose heparin as effective as activated protein C? Intensive Care Med. 2005 Sep;31(9):1297-8. doi: 10.1007/s00134-005-2723-0. Epub 2005 Jul 9. No abstract available.
Results Reference
background
PubMed Identifier
18824906
Citation
Zarychanski R, Doucette S, Fergusson D, Roberts D, Houston DS, Sharma S, Gulati H, Kumar A. Early intravenous unfractionated heparin and mortality in septic shock. Crit Care Med. 2008 Nov;36(11):2973-9. doi: 10.1097/CCM.0b013e31818b8c6b.
Results Reference
background
PubMed Identifier
16930112
Citation
Robertson MS. Heparin: the cheap alternative for immunomodulation in sepsis? Crit Care Resusc. 2006 Sep;8(3):235-8.
Results Reference
background
PubMed Identifier
12682480
Citation
Derhaschnig U, Pernerstorfer T, Knechtelsdorfer M, Hollenstein U, Panzer S, Jilma B. Evaluation of antiinflammatory and antiadhesive effects of heparins in human endotoxemia. Crit Care Med. 2003 Apr;31(4):1108-12. doi: 10.1097/01.CCM.0000059441.70680.DC.
Results Reference
background
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Safety of Heparin in Patients With Septic Shock
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