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

• ClinicalTrials.gov Identifier: NCT04640181
• Recruitment Status: Not yet recruiting
• First Posted: November 23, 2020
• Last Update Posted: November 23, 2020
• Sponsor: St. David's HealthCare
• Information provided by (Responsible Party): St. David's HealthCare

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Covid19	Drug: Enoxaparin; Drug: Rivaroxaban	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.
• Masking: None (Open Label)
• Masking Description: Open label
• Primary Purpose: Treatment
• 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)
• Estimated Study Start Date: December 1, 2020
• Estimated Primary Completion Date: June 30, 2021
• Estimated Study Completion Date: July 31, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Death or 30-day all cause mortality [ Time Frame: 30 days ]
2. Mechanical ventilation, intubation [ Time Frame: 30 days ]
3. Transfer to an ICU setting [ Time Frame: 30 days ]

Secondary Outcome Measures :

1. New requirement for hemodialysis (HD) or continuous renal replacement therapy (CRRT) or extracorporeal membrane oxygenation (ECMO) [ Time Frame: 30 days ]
2. New thrombotic events [ Time Frame: 30 days ]
3. Major bleeding event [ Time Frame: 30 days ]
4. Time to recovery (defined as no limitation or minor limitation in activity level or hospitalized but require no oxygen) [ Time Frame: 30 days ]

Eligibility Criteria

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

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.

Contacts and Locations

Contacts

Contact: Matt Cowperthwaite, PhD; 512-544-2626; info@stdavidsresearch.com

Contact: Theresa Pham, MD; theresa.pham@ppdi.com

Sponsors and Collaborators

St. David's HealthCare

Investigators

• Principal Investigator: Edward Chafizadeh, MD; Cardio Texas, PLLC
• Principal Investigator: Theresa Pham, MD; PPD Austin

More Information

Additional Information:

Drug information for Enoxaparin sodium provided by the National Library of Medicine 

Xarelto (rivaroxaban) full prescribing information 

• Responsible Party: St. David's HealthCare
• ClinicalTrials.gov Identifier: NCT04640181
• Other Study ID Numbers: 2020-001708-41
• First Posted: November 23, 2020
• Last Update Posted: November 23, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Keywords provided by St. David's HealthCare:

Coronavirus; Enoxaparin; Rivaroxaban; Anticoagulants; Anti-inflammatory; Anti-viral; ARDS

Additional relevant MeSH terms:

Enoxaparin; Rivaroxaban; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents