Factor Xa Inhibitor Versus Standard of Care Heparin in Hospitalized Patients With COVID-19 (XACT)

A Phase 2-3, Multi-Center, Randomized Trial to Study the Potential Benefit of Factor Xa Inhibitor (Rivaroxaban) Versus Standard of Care Low Molecular Weight Heparin (Lovenox) in Hospitalized Patients With COVID-19 (XACT)

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.

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.

Inclusion Criteria:

• Patients age 18-100 admitted to hospital with laboratory-confirmed SARS-CoV-2 infection
• Not be intubated or mechanically ventilated or imminently at risk for same or ICU admission within 24 hours of enrollment.
• Not be admitted for central nervous system (CNS) diagnosis
• Not have a current history of a condition requiring full therapeutic anticoagulation such as venous thromboembolism, atrial fibrillation.

Exclusion Criteria:

Medical Conditions

• Life expectancy of less than 6 months
• Active or recent gastrointestinal bleeding in the past 6 months
• Intracranial bleeding in the past 6 months
• Major trauma or head trauma in the past 2 months
• Major surgery in the past 2 months or planned within 2 weeks after completion of the study
• Recent spinal or epidural procedures in the past 2 weeks
• Ischemic stroke in the past 2 weeks
• History of intracranial neoplasm, arteriovenous malformation or aneurysm
• 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
• Allergy to heparin or rivaroxaban or any factor Xa inhibitors, including a history of heparin-induced thrombocytopenia
• History of antiphospholipid syndrome
• End-stage renal failure requiring dialysis
• Valvular heart disease requiring chronic anticoagulation
• History of atrial fibrillation, atrial flutter or venous thromboembolic event (VTE) currently requiring anticoagulation
• History of solid organ transplant requiring immunosuppressant therapy
• Cancer requiring ongoing anticoagulation
• History of cirrhosis or liver failure, hepatorenal syndrome
• History of baseline bronchiectasis
• 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

• PT INR > 2.0.
• Platelet < 90 10^3/µL
• Total bilirubin > 3.0 mg/dL
• Hemoglobin < 9.0 g/dL
• Urine with gross hematuria (not due to menses)
• Estimated glomerular filtration rate (GFR) less than 30 mL/min calculated with the Cockcroft-Gault formula

Medications

• Patients on dual anti-platelet therapy
• Patients taking hypoxia-inducible factor prolyl hydroxylase inhibitors (such as roxadustat.)
• Erythropoiesis-stimulating agents (such as epoetin alfa, darbepoetin alfa)

Other COVID-19 drug studies or trials

• Any COVID19 vaccination trials
• Experimental COVID drug trial except for treatment(s) that has become accepted standard of care.