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.
Drug: Enoxaparin
Subcutaneous enoxaparin While hospitalized only.
Drug: Rivaroxaban
Oral rivaroxaban While hospitalized and through discharge for a total of 28 days.
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.
St. David's Medical Center
Austin, Texas, United States