Factor Xa Inhibitor Versus Standard of Care Heparin in Hospitalized Patients With COVID-19 (XACT)
Study Details
Study Description
Brief Summary
This study is a multicenter, randomized trial to study the potential benefit of treatments with a direct FXa inhibitor (rivaroxaban) versus standard of care dose subcutaneous low molecular weight heparin (LMWH) (Lovenox) in hospitalized subjects with COVID-19.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Detailed Description
As clinicians learn how to better care for hospitalized COVID-19 patients, the clinical picture of a hypercoagulable state with abnormal blood clotting has emerged. Fulminant heart, lung, kidney, and liver failure are hallmarks of COVID-19 non-survivors and have been associated with abnormal blood coagulation parameters, such as elevated D-Dimer levels. The current standard of care using prophylactic levels of subcutaneous heparin has not significantly mitigated the risk of patients entering a hypercoagulable state, however the dysregulated thrombotic and inflammatory events that drive poor outcomes in many COVID-19 patients may be amenable to early treatment with a factor Xa (FXa) inhibitor. The purpose of this study is to study the potential benefit of treatments with a direct FXa inhibitor (rivaroxaban) versus standard of care dose subcutaneous LMWH (Lovenox) in hospitalized subjects with COVID-19.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Adaptive Dosing: Enoxaparin Low 40mg subcutaneous (SQ) daily, or Intermediate 40mg SQ q12 hours, or Therapeutic 1mg/kg SQ q12 hours |
Drug: Enoxaparin
Subcutaneous enoxaparin While hospitalized only.
|
Active Comparator: Adaptive Dosing: Rivaroxaban Low 10mg po daily Intermediate 10mg po daily Therapeutic 20mg po daily |
Drug: Rivaroxaban
Oral rivaroxaban While hospitalized and through discharge for a total of 28 days.
|
Outcome Measures
Primary Outcome Measures
- Death or 30-day all cause mortality [30 days]
- Mechanical ventilation, intubation [30 days]
- Transfer to an ICU setting [30 days]
Secondary Outcome Measures
- New requirement for hemodialysis (HD) or continuous renal replacement therapy (CRRT) or extracorporeal membrane oxygenation (ECMO) [30 days]
- New thrombotic events [30 days]
- Major bleeding event [30 days]
- Time to recovery (defined as no limitation or minor limitation in activity level or hospitalized but require no oxygen) [30 days]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients age 18-100 admitted to hospital with laboratory-confirmed SARS-CoV-2 infection
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Not be intubated or mechanically ventilated or imminently at risk for same or ICU admission within 24 hours of enrollment.
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Not be admitted for central nervous system (CNS) diagnosis
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Not have a current history of a condition requiring full therapeutic anticoagulation such as venous thromboembolism, atrial fibrillation.
Exclusion Criteria:
Medical Conditions
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Life expectancy of less than 6 months
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Active or recent gastrointestinal bleeding in the past 6 months
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Intracranial bleeding in the past 6 months
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Major trauma or head trauma in the past 2 months
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Major surgery in the past 2 months or planned within 2 weeks after completion of the study
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Recent spinal or epidural procedures in the past 2 weeks
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Ischemic stroke in the past 2 weeks
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History of intracranial neoplasm, arteriovenous malformation or aneurysm
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History of acquired or spontaneous impairment of hemostasis such as but not limited to hemophilia, idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), von Willebrand disease
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Allergy to heparin or rivaroxaban or any factor Xa inhibitors, including a history of heparin-induced thrombocytopenia
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History of antiphospholipid syndrome
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End-stage renal failure requiring dialysis
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Valvular heart disease requiring chronic anticoagulation
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History of atrial fibrillation, atrial flutter or venous thromboembolic event (VTE) currently requiring anticoagulation
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History of solid organ transplant requiring immunosuppressant therapy
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Cancer requiring ongoing anticoagulation
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History of cirrhosis or liver failure, hepatorenal syndrome
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History of baseline bronchiectasis
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History of systemic lupus erythematosus or other autoimmune diseases requiring immunosuppressant therapy.
Vital signs
- Uncontrolled hypertension: systolic blood pressure (SBP) > 180 mm Hg or diastolic blood pressure (DBP) > 105mm Hg. Subjects who have a transient, higher blood pressure elevation (SBP 180-200 mm Hg) may enter the study if a repeat confirmation is back in range prior to enrollment.
Laboratory
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PT INR > 2.0.
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Platelet < 90 10^3/µL
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Total bilirubin > 3.0 mg/dL
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Hemoglobin < 9.0 g/dL
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Urine with gross hematuria (not due to menses)
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Estimated glomerular filtration rate (GFR) less than 30 mL/min calculated with the Cockcroft-Gault formula
Medications
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Patients on dual anti-platelet therapy
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Patients taking hypoxia-inducible factor prolyl hydroxylase inhibitors (such as roxadustat.)
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Erythropoiesis-stimulating agents (such as epoetin alfa, darbepoetin alfa)
Other COVID-19 drug studies or trials
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Any COVID19 vaccination trials
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Experimental COVID drug trial except for treatment(s) that has become accepted standard of care.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | St. David's Medical Center | Austin | Texas | United States | 78705 |
Sponsors and Collaborators
- St. David's HealthCare
Investigators
- Principal Investigator: Edward Chafizadeh, MD, Cardio Texas, PLLC
- Principal Investigator: Theresa Pham, MD, PPD Austin
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Drug information for Enoxaparin sodium provided by the National Library of Medicine
- Xarelto (rivaroxaban) full prescribing information
Publications
None provided.- 2020-001708-41