Covid19
Conditions
Keywords
Coronavirus, Enoxaparin, Rivaroxaban, Anticoagulants, Anti-inflammatory, Anti-viral, ARDS
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.
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.
Interventions
DRUGEnoxaparin
Subcutaneous enoxaparin While hospitalized only.
DRUGRivaroxaban
Oral rivaroxaban While hospitalized and through discharge for a total of 28 days.
Sponsors
St. David's HealthCare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label
Intervention model description
Open-label Multicenter Prospective Randomized Trial in hospitalized patients with severe acute respiratory syndrome (SARS)-CoV-2 infection. Patients will be randomized 1:1 to subcutaneous enoxaparin (Lovenox) versus rivaroxaban after hospitalization, with the exact dosing is based on an adaptive strategy.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Death or 30-day all cause mortality | 30 days |
| Mechanical ventilation, intubation | 30 days |
| Transfer to an ICU setting | 30 days |
Secondary
| Measure | Time frame |
|---|---|
| New requirement for hemodialysis (HD) or continuous renal replacement therapy (CRRT) or extracorporeal membrane oxygenation (ECMO) | 30 days |
| Time to recovery (defined as no limitation or minor limitation in activity level or hospitalized but require no oxygen) | 30 days |
| New thrombotic events | 30 days |
| Major bleeding event | 30 days |
Countries
United States
Outcome results
None listed