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This study will assess the safety and effectiveness of a drug called apixaban for the treatment of upper extremity deep vein thrombosis (UEDVT) and clinically important bleeding. Subjects will receive apixaban 10 mg by mouth twice a day for 7 days, followed by 5 mg by mouth twice a day for a duration of 11 weeks. There will be a followup visit at 12 weeks for all participants. A total of 375 are to be enrolled.

The study drug has been approved to treat blood clots. The study drug has not been studied uniquely for the treatment of blood clots in the upper extremity however. Because it is unknown whether it is effective to treat blood clots in the upper extremity, the principal investigator cannot guarantee that there will be benefit to study subjects; however, it is hoped that the information obtained from this research study will help treat patients in the future.

Background: Upper extremity deep vein thrombosis (UEDVT) constitutes approximately 10% of all DVT. A recent increase in incidence is largely secondary to the increasing use of peripherally inserted central venous catheters. Treatment for UEDVT is derived from evidence for treatment of lower extremity deep vein thrombosis (LEDVT). No evidence exists for the use of a direct oral anticoagulant (DOAC) for the treatment of UEDVT.

Population: Sequential patients identified within the Intermountain Healthcare system with UEDVT defined as the formation of thrombus within the internal jugular, subclavian, axillary, and brachial veins of the arm demonstrated by imaging.

Comparison: In the primary analysis, the principal investigator will report the rate of clinically overt objective VTE and VTE-related death in comparison to the rate reported upon literature review ("reference value in the literature"). If the confidence interval for this rate excludes the commonly accepted threshold event rate of 4%, the principal investigator will conclude that treatment with apixaban is noninferior, and therefore a clinically valid approach to treat UEDVT. As a secondary analysis, the principal investigator will compare the rate of the primary efficacy outcome and primary safety outcome with a historical control of case matched patients with UEDVT ("historical control") treated with therapy conventional (low molecular weight heparin plus warfarin) prior to the approval of DOACs.

Sample Size: A sample size of 357 patients who meet eligibility criteria was chosen so that an exact 95% confidence interval would exclude an event rate of venous thromboembolism (VTE) in the observation cohort of 4%. The principal investigator will add 5% for anticipated withdrawal to assure adequate patient enrollment in the case of patient withdrawal and enroll 375 patients.

Outcome: 90 day rate of new or recurrent objectively confirmed symptomatic venous thrombosis and VTE-related death. The primary safety outcome is major bleeding and clinically relevant nonmajor bleeding.

Inclusion Criteria:

• Be ≥ 18 years of age
• Have received no more than six (6) doses of any therapeutic anticoagulant, or intravenous and bridging heparin for longer than 72 hours
• Women must not be breastfeeding
• Receiving apixaban as administered per clinical routine (apixaban 10 mg by mouth twice daily for 7 days, followed by apixaban 5 mg twice daily for 11 weeks)
• Provide informed consent within 72 hours of receiving apixaban

Exclusion Criteria:

• Another indication for long-term anticoagulation for which no FDA approval of apixaban exists (e.g. prosthetic heart valves)
• Life expectancy of less than 6 months
• Unable to engage in reliable follow-up as per protocol
• Participating in a clinical trial or has participated in a clinical trial within the last 30 days
• Receiving concomitant dual antiplatelet therapy
• Requires aspirin dose of greater than 165 mg daily
• Intend pregnancy or breastfeeding within the next year
• Known allergy to apixaban, rivaroxaban, or edoxaban
• Active pathological bleeding.
• Any condition that at the discretion of the investigator is thought to prohibit active participation and follow-up in the trial
• UEDVT that occurs while therapeutic anticoagulation is being taken by the patient ("event on therapy")
• The patient has concomitant VTE diagnosed elsewhere except deep vein thrombosis that has its most proximal aspect in the distal veins ("isolated distal DVT")
• Any contraindication to apixaban referenced in the package insert