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

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: Enoxaparin; Drug: Rivaroxaban

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 Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78705
      • St. David's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: St. David's HealthCare
• Investigators: Principal Investigator: Edward Chafizadeh, MD, Cardio Texas, PLLC; Principal Investigator: Theresa Pham, MD, PPD Austin

Publications and helpful links

Helpful Links

• Xarelto (rivaroxaban) full prescribing information

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Actual): June 28, 2021
• Study Completion (Actual): June 28, 2021

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: November 19, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Actual): June 30, 2021
• Last Update Submitted That Met QC Criteria: June 28, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Rivaroxaban; Coronavirus; ARDS; Enoxaparin; Anti-inflammatory; Anticoagulants; Anti-viral
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Enoxaparin
• Other Study ID Numbers: 2020-001708-41

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes