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

Sponsor
St. David's HealthCare (Other)
Overall Status
Completed
CT.gov ID
NCT04640181
Collaborator
(none)
150
1
2
6.9
21.8

Study Details

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
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
Actual 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.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)
Actual Study Start Date :
Dec 1, 2020
Actual Primary Completion Date :
Jun 28, 2021
Actual Study Completion Date :
Jun 28, 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 [30 days]

  2. Mechanical ventilation, intubation [30 days]

  3. Transfer to an ICU setting [30 days]

Secondary Outcome Measures

  1. New requirement for hemodialysis (HD) or continuous renal replacement therapy (CRRT) or extracorporeal membrane oxygenation (ECMO) [30 days]

  2. New thrombotic events [30 days]

  3. Major bleeding event [30 days]

  4. Time to recovery (defined as no limitation or minor limitation in activity level or hospitalized but require no oxygen) [30 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 100 Years
Sexes Eligible for Study:
All
Accepts 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 St. David's Medical Center Austin Texas United States 78705

Sponsors and Collaborators

  • St. David's HealthCare

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
St. David's HealthCare
ClinicalTrials.gov Identifier:
NCT04640181
Other Study ID Numbers:
  • 2020-001708-41
First Posted:
Nov 23, 2020
Last Update Posted:
Jun 30, 2021
Last Verified:
Jun 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 30, 2021