Safety of Heparin in Patients With Septic Shock - Full Text View

Purpose

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	Intervention	Phase
Sepsis	Drug: heparin	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Safety of Heparin Anticoagulation for Prevention of Death in Patients With Septic Shock.

Resource links provided by NLM:

MedlinePlus related topics: Blood Thinners Sepsis Shock

Drug Information available for: Heparin

U.S. FDA Resources

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:

Incidence of major bleeding [ Time Frame: This outcome will be measured for an average of 30 days ] [ Designated as safety issue: Yes ]
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.

Estimated Enrollment:	100
Study Start Date:	December 2010
Estimated Study Completion Date:	October 2013
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Eligibility

Ages Eligible for Study:	18 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 -

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01234285

Contacts

Contact: Elizabeth Luzier, RN

303-724-3597

elizabeth.luzier@ucdenver.edu

Locations

United States, Colorado
University of Colorado Hospital	Recruiting
Aurora, Colorado, United States, 80045

Sponsors and Collaborators

University of Colorado, Denver

Investigators

Principal Investigator:

Sara Cheng, MD;PhD

University of Colorado, Denver

More Information

Publications:

Marshall JC. Inflammation, coagulopathy, and the pathogenesis of multiple organ dysfunction syndrome. Crit Care Med. 2001 Jul;29(7 Suppl):S99-106. Review.

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. Epub 2005 Jul 9. No abstract available.

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.

Robertson MS. Heparin: the cheap alternative for immunomodulation in sepsis? Crit Care Resusc. 2006 Sep;8(3):235-8. Review.

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.

Responsible Party:	University of Colorado, Denver
ClinicalTrials.gov Identifier:	NCT01234285 History of Changes
Other Study ID Numbers:	10-0595
Study First Received:	September 23, 2010
Last Updated:	November 21, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:

sepsis
septic shock
anticoagulation
intensive care unit

Additional relevant MeSH terms:

Sepsis
Shock
Shock, Septic
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Calcium heparin
Heparin

Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 16, 2013