Factor XI Levels in Acute Ischemic Stroke

Stroke Clinical Trial

Official title:

Factor XI Levels in Acute Ischemic Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00890812
• Other study ID #: 14363
• Secondary ID: ACC: 46499140IRB
• Status: Completed
• Phase: N/A
• First received: April 28, 2009
• Last updated: August 2, 2011
• Start date: May 2009
• Est. completion date: July 2011

Study information

• Verified date: August 2011
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to evaluate the utility of measuring coagulation factor activities in the setting of acute ischemic stroke, as potential markers of inherited thrombotic risk. The investigators will determine if relationships exist between coagulation factors, including factor VIII, factor IX, and factor XI and clinical diagnosis, classification, and outcome. The investigators will determine if any significant elevations of these factor activities are independent thrombotic risk factors.

Null Hypothesis: There is no statistical difference between coagulation factors, including factors VIII, IX, or XI activity levels in patients having acute ischemic stroke as compared to acute stroke mimics.

Description:

Increased factor XI levels have been associated with venous thromboembolic disease and acute myocardial infarction. However, checking factor XI levels is not currently indicated to assess individual thromboembolic risk. Factor XI is an important protease that links the extrinsic arm of the coagulation cascade with the intrinsic arm through dual activation by both factor XII and thrombin. Since thrombin is a downstream product of factor XI, a feedback loop is created that amplifies thrombin production and ultimately results formation of a stable fibrin clot. Sufficient thrombin generation via this pathway also contributes to activation of the Thrombin-Activatable Fibrinolysis Inhibitor (TAFI). Activated TAFI downregulates fibrinolysis and has been implicated as part of the association between elevated factor XI levels and venous thromboembolic disease. One study found that functional TAFI levels of > 120% increased the risk of ischemic stroke approximately 6-fold, however, the association between Factor XI and ischemic stroke has yet to be firmly established. We recently performed a preliminary retrospective analysis of 78 patients with stroke or transient ischemic attack (TIA) and found that patients with factor XI activity levels above the 95th percentile of an age and sex matched reference population had a relative risk of 5.3 for stroke or TIA. Factor XI measurements may be able to help identify thromboembolic disease, aiding in the determination of stroke etiology.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 450
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Those clinically diagnosed with acute ischemic stroke

• 18 years of age or greater

Exclusion Criteria:

• Those without clinical diagnosis of acute ischemic stroke will be included in the control group.

• Patients with hemorrhagic strokes

• Inpatients who are evaluated through the Brain Attack protocol

Study Design

Observational Model: Case Control, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Stroke

Locations

Country	Name	City	State
United States	University of Utah Health Sciences Center	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
University of Utah	Sheila B. Terry Memorial Research Fund

Country where clinical trial is conducted

United States, 

References & Publications (7)

Chandler WL, Rodgers GM, Sprouse JT, Thompson AR. Elevated hemostatic factor levels as potential risk factors for thrombosis. Arch Pathol Lab Med. 2002 Nov;126(11):1405-14. Review. — View Citation

Meijers JC, Tekelenburg WL, Bouma BN, Bertina RM, Rosendaal FR. High levels of coagulation factor XI as a risk factor for venous thrombosis. N Engl J Med. 2000 Mar 9;342(10):696-701. — View Citation

Minnema MC, Peters RJ, de Winter R, Lubbers YP, Barzegar S, Bauer KA, Rosenberg RD, Hack CE, ten Cate H. Activation of clotting factors XI and IX in patients with acute myocardial infarction. Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):2489-93. — View Citation

Murakami T, Komiyama Y, Masuda M, Karakawa M, Iwasaka T, Takahashi H. Evaluation of factor XIa-alpha 1-antitrypsin in plasma, a contact phase-activated coagulation factor-inhibitor complex, in patients with coronary artery disease. Arterioscler Thromb Vas — View Citation

Salomon O, Steinberg DM, Koren-Morag N, Tanne D, Seligsohn U. Reduced incidence of ischemic stroke in patients with severe factor XI deficiency. Blood. 2008 Apr 15;111(8):4113-7. doi: 10.1182/blood-2007-10-120139. Epub 2008 Feb 11. — View Citation

Santamaría A, Oliver A, Borrell M, Mateo J, Belvis R, Martí-Fábregas J, Ortín R, Tirado I, Souto JC, Fontcuberta J. Risk of ischemic stroke associated with functional thrombin-activatable fibrinolysis inhibitor plasma levels. Stroke. 2003 Oct;34(10):2387- — View Citation

Yang DT, Flanders MM, Kim H, Rodgers GM. Elevated factor XI activity levels are associated with an increased odds ratio for cerebrovascular events. Am J Clin Pathol. 2006 Sep;126(3):411-5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the relationship between elevated factors VIII, IX and XI and acute ischemic stroke as compared to other emergent events.		At time of incident stroke (baseline) and at early follow-up (30-60 Days post stroke).	No
Secondary	To determine the relationship between elevated factors VIII, IX and XI and stroke subtype.		30-60 Days post stroke	No
Secondary	To determine if a relationship exists between elevated factors VIII, IX and XI and the clinical severity and stroke outcome.		30-60 Days post stroke	No
Secondary	To determine if factors VIII, IX and XI level are different in the acute phase of ischemic stroke relative to chronic phase.		30-60 Days post stroke	No
Secondary	To determine if a relationship exists between factors VIII, IX and XI levels and early stroke/TIA recurrence.		30-60 Days post stroke	No