Safety of Heparin in Patients With Septic Shock

NCT01234285 | Withdrawn Phase 2 DMC

• 1 other identifier: 10-0595
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis

Keywords

sepsis; septic shock; anticoagulation; intensive care unit

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (4)

intravenous heparin aPTT 40-50 seconds

EXPERIMENTAL

Patients 11-15: IV heparin, target aPTT range 40-50 seconds

Drug: heparin

intravenous heparin

EXPERIMENTAL

Patients 26-40: IV heparin, target range aPTT 50-60 seconds

Drug: heparin

Intravenous heparin

EXPERIMENTAL

Patients 41-55 IV heparin, target aPTT range 60-70 seconds

Drug: heparin

sq heparin three times a day

ACTIVE COMPARATOR

Patients 1-10 will receive subcutaneous heparin three times a day

Drug: heparin

Interventions

heparin DRUG

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.

intravenous heparin aPTT 40-50 seconds

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 -

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Related Publications (5)

• 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.

  PMID: 11445742 BACKGROUND

• 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.

  PMID: 16007415 BACKGROUND

• 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.

  PMID: 18824906 BACKGROUND

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

  PMID: 16930112 BACKGROUND

• 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.

  PMID: 12682480 BACKGROUND

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Heparin

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Sara Cheng, MD;PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2010
• First Posted: November 4, 2010
• Study Start: December 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: October 1, 2013
• Last Updated: May 20, 2014

Record last verified: 2014-05

Locations

US (1)