Clinical trial NCT04640181: Factor Xa Inhibitor Versus Standard of Care Heparin in Hospitalized Patients With COVID-19 (XACT)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Keywords: Coronavirus
Enoxaparin
Rivaroxaban
Anticoagulants
Anti-inflammatory
Anti-viral
ARDS
Lead sponsor: St. David's HealthCare
Sponsor class: OTHER
First posted: 2020-11-23
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Death or 30-day all cause mortality
timeFrame: 30 days
measure: Mechanical ventilation, intubation
timeFrame: 30 days
measure: Transfer to an ICU setting
timeFrame: 30 days
Secondary outcomes:
measure: New requirement for hemodialysis (HD) or continuous renal replacement therapy (CRRT) or extracorporeal membrane oxygenation (ECMO)
timeFrame: 30 days
measure: New thrombotic events
timeFrame: 30 days
measure: Major bleeding event
timeFrame: 30 days
measure: Time to recovery (defined as no limitation or minor limitation in activity level or hospitalized but require no oxygen)
timeFrame: 30 days
Other outcomes:
Locations:
city: Austin
country: United States
facility: St. David's Medical Center
state: Texas
Study officials:
affiliation: Cardio Texas, PLLC
name: Edward Chafizadeh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: PPD Austin
name: Theresa Pham, MD
role: PRINCIPAL_INVESTIGATOR
References: