Summary

• EXPLORER is a global cardiovascular (CV) research program for XARELTO (rivaroxaban). This program for XARELTO was launched by Janssen in 2013 in order to explore a broader indication profile and to improve patient outcomes in the CV setting. Supported by data from the EXPLORER program, XARELTO has eight indications. As a highly selective Factor Xa inhibitor, XARELTO is indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF), treatment of deep vein thrombosis (DVT), treatment of pulmonary embolism (PE), reduction in the risk of recurrence of DVT and/or PE in patients at continued risk for recurrent DVT and/or PE, prophylaxis of DVT following hip or knee replacement surgery, prophylaxis of VTE in acutely ill medical patients at risk for thromboembolic complications not at high risk of bleeding, reduction of risk of major cardiovascular events in patients with coronary artery disease (CAD), and for the reduction of risk of major thrombotic vascular events in patients with peripheral artery disease (PAD). Trials in this program have investigated the safety and efficacy of XARELTO for conditions including heart failure, embolic stroke of undetermined source (ESUS), acute coronary syndrome, and active cancer.  
• For additional information on these clinical studies, please refer to the individual associated publications and/or to https://clinicaltrials.gov/.

EXPLORER CLINICAL STUDIES

The clinical studies included in the global EXPLORER research program are listed below in Table: EXPLORER Program Studies.

APPROVED INDICATIONS

Reduced the Risk of Stroke & Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation

• ROCKET AF¹ (Rivaroxaban, Once-daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial and Atrial Fibrillation) trial was a phase 3, randomized, double-blind, double-dummy, active-controlled, parallel-group, multicenter, event-driven, noninferiority study to evaluate the efficacy and safety of oral fixed-dose XARELTO 20 mg once daily (15 mg for patients with creatinine clearance [CrCl] 30-49 mL/min) and dose-adjusted warfarin (target international normalized ratio [INR]: 2.0 to 3.0) for the prevention of stroke and systemic embolism in patients with nonvalvular AF at moderate-to-high risk for stroke
• J ROCKET AF² (Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation) was a phase 3, prospective, randomized, double blind, double dummy, parallel group, active controlled, multicenter, noninferiority study that evaluated the safety of XARELTO versus warfarin in Japanese patients with non-valvular AF.

Treatment of DVT or PE

• EINSTEIN-DVT³ (Oral rivaroxaban for symptomatic venous thromboembolism) was a phase 3, randomized, open-label, event-driven, noninferiority trial that compared oral XARELTO alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin (1.0 mg/kg twice daily) followed by dose-adjusted oral vitamin K antagonist (VKA) (warfarin or acenocoumarol) in patients with confirmed symptomatic deep vein thrombosis (DVT) without symptomatic pulmonary embolism (PE).
• EINSTEIN-PE⁴ (Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism) was a phase 3, randomized, open-label, event-driven, noninferiority study evaluating the efficacy and safety of oral XARELTO (15 mg twice daily for 3 weeks followed by 20 mg once daily) versus subcutaneous enoxaparin (1.0 mg/kg twice daily) followed by dose-adjusted oral VKA in patients with acute symptomatic PE with or without DVT.

Reduction in the Risk of Recurrence of DVT and /or PE

• EINSTEIN-EXTENSION⁵ (Oral rivaroxaban after symptomatic venous thromboembolism: the continued treatment study) was a phase 3 randomized, double-blind, placebo-controlled, event driven, superiority study evaluating the efficacy of XARELTO (20 mg daily) versus placebo (daily) in patients with confirmed symptomatic PE or DVT who have been treated for 6 to 12 months with VKA or XARELTO.
• EINSTEIN CHOICE⁶ (Comparison of rivaroxaban treatment and prophylactic doses with aspirin in the extended treatment of patients with venous thromboembolism) was a phase 3, randomized, double-blind study that compared the efficacy and safety of two doses of XARELTO (20 mg and 10 mg, once-daily) with aspirin (100 mg, once-daily) in 3365 patients with VTE who had completed 6-12 months of anticoagulation therapy and for whom there was equipoise with respect to the need for ongoing anticoagulation.

Prophylaxis of DVT following hip or knee replacement surgery (RECORD 1, 2, 3)

The RECORD studies were Phase 3, randomized, double-blind studies that assessed the efficacy and safety of XARELTO 10 mg once daily compared to subcutaneous enoxaparin therapy for VTE prevention in patients undergoing elective total knee replacement surgery or total hip arthroplasty.^7-9

Prophylaxis of VTE in Acutely Ill Medical Patients at risk for Thromboembolic Complications not at High Risk of Bleeding

• MAGELLAN¹⁰ (Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Patients) was a phase 3, international, randomized, double-blind trial designed to evaluate efficacy and safety of extended thromboprophylaxis with XARELTO compared with standard duration enoxaparin for the prevention of VTE in hospitalized acutely ill medical patients during the inpatient and post discharge periods.
• Additionally, a MAGELLAN subpopulation (that excluded subjects with active cancer, dual antiplatelet therapy at baseline, bronchiectasis/pulmonary cavitation, gastroduodenal ulcer, or bleeding within 3 months before randomization of MAGELLAN study) was assessed to reevaluate the benefit risk profile of XARELTO compared with enoxaparin for thromboprophylaxis.¹¹

Reduction of Risk of Major Cardiovascular Events in Patients with CAD

• COMPASS¹² (Cardiovascular Outcome for People Using Anticoagulation Strategies) was a phase 3, event-driven, double-blind, randomized study designed to evaluate whether treatment with XARELTO 2.5 mg twice daily (BID) plus aspirin 100 mg once daily or XARELTO 5 mg BID alone is more effective than aspirin 100 mg once daily alone for the prevention of myocardial infarction (MI), stroke, or cardiovascular (CV) death in patients with a history of stable atherosclerotic vascular disease (coronary artery disease [CAD] or peripheral artery disease [PAD]).

Reduction of Risk of Major Thrombotic Vascular Events in Patients with PAD

• The COMPASS study also evaluated the efficacy and safety of XARELTO 2.5 mg orally twice daily vs placebo on a background of aspirin 100 mg once daily in patients with PAD.
• VOYAGER PAD¹³(Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) was a phase 3, multicenter, randomized, placebo-controlled, double-blind, international study designed to evaluate whether XARELTO 2.5 mg BID plus aspirin 100 mg once daily is more effective than aspirin 100 mg once daily alone for risk reduction of major atherothrombotic vascular outcomes consisting of both CV and limb events in patients with symptomatic PAD undergoing lower-extremity revascularization.

VTE Treatment & Reduction in the Risk of Recurrent VTE in Pediatric Patients from Birth to <18 years of age after at least 5 days of Initial Parenteral Treatment

• EINSTEIN JUNIOR PROGRAM:
  • EINSTEIN JUNIOR PHASE 3:
    • Phase 3, multicenter, open-label, active-controlled, randomized study to evaluate the efficacy and safety of an age-and body weight-adjusted XARELTO regimen compared to standard of care in children (up to 17 years of age) with acute VTE.^14,15

Thromboprophylaxis in Pediatric patients (≥2 years of age) with Congenital Heart Disease after the Fontan Procedure

• UNIVERSE¹⁶ (Rivaroxaban, a Direct Factor Xa Inhibitor, versus Acetylsalicylic Acid as Thromboprophylaxis in Children Post-Fontan Procedure: Rationale and Design of a Prospective, Randomized Trial) is a phase 3, randomized, parallel-group, open-label study designed to characterize the single- and multiple-dose PK and PK/PD profiles following oral XARELTO administration to pediatric participants with single-ventricle physiology, who have completed the Fontan procedure within 4 months prior to enrollment (part A). This study will also evaluate the safety and efficacy of XARELTO compared to aspirin for thromboprophylaxis in pediatric participants 2 to 8 years of age with single-ventricle physiology, who have completed the Fontan procedure within 4 months prior to enrollment (part B).
  • Dosing interventions include:
    • XARELTO (dose based on weight) twice daily (parts A and B)
    • Aspirin 5 mg/kg once daily for up to 12 months (part B)
  • Primary outcome: maximum observed plasma concentration, area under the plasma concentration-time curve from time 0 to 24 hours, maximum observed plasma concentration at steady state, minimum observed plasma concentration at steady state, absolute prothrombin time, activated partial thromboplastin time, anti-factor Xa, number of participants with major bleeding events, and number of participants with incidence of thrombotic events up to 12 months.

COMPLETED STUDIES

The RECORD clinical development program, a comprehensive program of 4 phase III studies with over 12,000 patients, studied XARELTO^® (rivaroxaban tablets) for the prophylaxis of venous thromboembolism (VTE) in patients undergoing knee (RECORD 3 and 4) or hip (RECORD 1 and 2) replacement surgery.  The data from the RECORD program were submitted to the FDA.  XARELTO^® was approved on July 1, 2011 by the FDA for the indication studied in the RECORD program.

In the RECORD 4 study, patients received either oral XARELTO 10 mg once daily, beginning at least 6–8 h after surgery, or subcutaneous enoxaparin 30 mg every 12 hours, starting 12–24 hours after surgery.  Data from RECORD 4 are not included in the approved product labeling for XARELTO^®.

Since publication of RECORD 4 findings, the sponsor company conducted a verification of the data for all patients in this clinical trial.  With respect to study findings, additional adverse events/serious adverse events were identified; however, the distribution of those was balanced between study groups. In the company’s view, verification findings did not appreciably change the conclusions of the study. Thus, the RECORD 4 findings reported in the publication remain consistent with the overall results from the total RECORD program.

VTE Prophylaxis Following Knee or Hip Replacement Surgery (RECORD 4)

• The RECORD studies were Phase 3, randomized, double-blind studies that assessed the efficacy and safety of XARELTO 10 mg once daily compared to subcutaneous enoxaparin therapy for VTE prevention in patients undergoing elective total knee replacement surgery or total hip replacement surgery.¹⁷

Reduce the Risk of Stroke or Non-Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation

• mSToPS¹⁸ (Effect of a Home-Based Wearable Continuous ECG Monitoring Patch on Detection of Undiagnosed Atrial Fibrillation) was an investigator-initiated, randomized, pragmatic, site less clinical trial that evaluated the effect of a self-applied wearable electrocardiogram (ECG) patch in detecting AF and the clinical consequences associated with such a detection strategy.
• XANTUS¹⁹ (A Real-World, Prospective, Observational Study of Patients treated with Rivaroxaban for Stroke Prevention in Atrial Fibrillation) was an international, prospective, observational study designed to assess the efficacy and safety of XARELTO to prevent stroke or non-CNS systemic embolism in patients with non-valvular atrial fibrillation. The primary outcome is number of adjudicated treatment-emergent thromboembolic and bleeding events after 1 year or until 30 days after last dose of XARELTO.

VTE Prophylaxis in Medically Ill

• MARINER²⁰ (Medically Ill Patient Assessment of Rivaroxaban versus Placebo In Reducing Post-Discharge Venous Thrombo-Embolism Risk) trial was a phase 3, multicenter, randomized, double-blind, placebo-controlled, event-driven study that evaluated the efficacy and safety of XARELTO 10 mg once daily (7.5 mg once daily if creatinine clearance [CrCl] ≥30 to <50 mL/min) compared with placebo in the prevention of symptomatic VTE and VTE-related death after hospital discharge in high-risk, medically ill patients for a period of 45 days posthospital discharge.

Elective Cardioversion

• X-VERT^21,22 (Rivaroxaban vs. Vitamin K Antagonists for Cardioversion in Atrial Fibrillation) was a randomized, open-label, parallel group study that compared the efficacy and safety of XARELTO to dose-adjusted vitamin K antagonist (VKA) for the prevention of CV events in 1500 patients with nonvalvular AF scheduled for elective cardioversion. Patients were randomized in a 2:1 ratio (in favor of those receiving XARELTO).

Catheter Ablation

• VENTURE-AF^23,24 (Uninterrupted Rivaroxaban vs Uninterrupted Vitamin K Antagonists for Catheter Ablation in nonvalvular atrial fibrillation) was a randomized, open-label, active-controlled, multicenter study that evaluated the safety of XARELTO and uninterrupted VKA in adults with nonvalvular AF who underwent catheter ablation. During catheter ablation, heparin was administered and VKA was managed according to usual care. The next dose of XARELTO was administered at least 6 hours after hemostasis was established.

Heart Failure and Significant Coronary Artery Disease

• COMMANDER-HF²⁵ (Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease) was a phase 3, randomized, double-blind trial that assessed the efficacy and safety of XARELTO 2.5 mg twice daily compared with placebo in reducing the risk of all-cause mortality, myocardial infarction (MI), or stroke in participants with chronic heart failure (HF) and significant coronary artery disease (CAD), following a recent exacerbation of HF.

Percutaneous Coronary Intervention  

• PIONEER AF-PCI²⁶ (An open-label, randomized, controlled multicenter study exploring two treatment strategies of rivaroxaban and a dose-adjusted oral vitamin k antagonist treatment strategy in subjects with atrial fibrillation who undergo percutaneous coronary intervention) was a randomized, open-label, exploratory, phase 3 study that assessed the safety of two XARELTO treatment strategies (XARELTO 15 mg daily plus P2Y12 inhibitor for 12 months or XARELTO 2.5 mg twice daily plus 1, 6, or 12 months of dual antiplatelet therapy [DAPT]) and one VKA treatment strategy (target INR 2.0-3.0 plus 1, 6, or 12 months of DAPT) in patients who have paroxysmal, persistent, or permanent nonvalvular AF and have had a PCI with stent placement. The primary safety endpoint was TIMI clinically significant bleeding events (composite of TIMI major bleeding, minor bleeding, or bleeding requiring medical attention) during the treatment-emergent period (first study drug administration up to 2 days following drug discontinuation through 12 months of therapy).

Acute Coronary Syndrome

• GEMINI ACS 1²⁷ (Clinically Significant Bleeding with Low-Dose Rivaroxaban versus Aspirin in Addition to P2Y12 Inhibition, in Acute Coronary Syndromes) investigated the benefits of the dual pathway strategy of anticoagulation with XARELTO in combination with a single antiplatelet agent for long-term secondary prevention of additional CV events in patients with ACS. This study was a phase 2, multicenter, randomized, double-blind, parallel-group trial that compared low-dose XARELTO plus a P2Y12 inhibitor with aspirin plus a P2Y12 inhibitor in patients with unstable angina, non-ST segment elevation MI, or ST segment elevation MI, started within 10 days after presentation and continued for 6-12 months.
  • Patients were randomized to 1 of the following dosing interventions:
    • Active comparator (stratum 1/aspirin): Aspirin 100 mg once daily plus clopidogrel 75 mg once daily
    • Experimental (stratum 1/XARELTO): XARELTO 2.5 mg twice daily plus clopidogrel 75 mg once daily
    • Active comparator (stratum 2/aspirin): aspirin 100 mg once daily plus ticagrelor 90 mg twice daily
    • Experimental (stratum 2/XARELTO): XARELTO 2.5-mg tablet twice daily plus ticagrelor 90 mg twice daily
• ATLAS ACS-TIMI 46²⁸ (Rivaroxaban versus Placebo in Patients with Acute Coronary Syndromes) was a phase 2, randomized, double-blind, placebo-controlled, multicenter, dose-escalation and dose-confirmation study to evaluate the safety and efficacy of XARELTO in combination with Aspirin alone or with Aspirin and a Thienopyridine in subjects with ACS.
• ATLAS ACS 2 TIMI-51²⁹ (Anti-Xa Therapy to Lower Cardiovascular events in addition to Aspirin with/without thienopyridine therapy in Subjects with Acute Coronary Syndrome – Thrombolysis In Myocardial Infarction 51) was a phase 3, randomized, placebo-controlled, multicenter, event-driven study designed to determine whether XARELTO (2.5 mg twice daily [BID] or 5 mg BID), when added to standard care, is safe and reduces the risk of the composite of CV death, MI, or stroke in patients with a recent ACS.

Cancer VTE Prevention and Treatment  

• The CALLISTO Program³⁰:
  • CASSINI³¹ (Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer) was a phase 3, multicenter, randomized, double-blind study designed to evaluate efficacy and safety of XARELTO 10 mg once daily compared with placebo for prevention of cancer-associated thrombosis in ambulatory cancer patients who were initiated on systemic cancer therapy and at high risk for VTE. XARELTO did not significantly reduce VTE and VTE-related death for the intent-to-treat (ITT) population. In a supportive analysis of the on-treatment period (last dose plus 2 days), there was a substantially lower rate of VTE and VTE-related death. Thirty-nine percent of the events occurred following the discontinuation of the trial regimen. Incidence of major bleeding was low.
  • PRO-LAPS II³² (Rivaroxaban or Placebo for Extended Antithrombotic Prophylaxis after Laparoscopic Surgery for Colorectal Cancer) is a phase 3, investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial that assessed the efficacy and safety of post-discharge extended (3 weeks) antithrombotic prophylaxis with XARELTO 10 mg vs placebo after planned laparoscopic surgery for colorectal cancer.
  • COSIMO³⁰ (Patients with Active Cancer changing to Rivaroxaban for the Treatment and Prevention of recurrent Venous Thromboembolism: A Non-Interventional Study) is an international, prospective, noninterventional, observational, cohort registry designed to assess patient-reported treatment satisfaction with regard to the Anti-Clot Treatment Scale burden score related to use of XARELTO for the treatment of acute VTE and prevention of recurrent VTE in patients with active cancer changing to this therapy.
  • SELECT-D³³ (Comparison of an Oral Factor Xa Inhibitor with Low Molecular Weight Heparin in Patients with Cancer With Venous Thromboembolism) is a prospective, randomized, open-label, multicenter study designed to assess the efficacy and safety of XARELTO vs dalteparin for the treatment of VTE in patients with cancer.
  • CASTA-DIVA³⁴ (Rivaroxaban versus Dalteparin in Cancer-Associated Thromboembolism: A Randomized Trial) is a prospective, multicenter, randomized, open-label, noninferiority study with blinded adjudication of endpoints designed to assess the efficacy and safety of XARELTO vs dalteparin for the treatment of VTE in patients with active cancer at high risk of VTE recurrence.
  • QAI³⁵ (Safe and Effective Use of Rivaroxaban for Treatment of Cancer-Associated Venous Thromboembolic Disease: A Prospective Cohort Study) is a prospective cohort study that established a clinical pathway to guide XARELTO treatment for cancer-associated thrombosis (PE or symptomatic, proximal DVT).
  • CONKO-011³⁶ (Evaluation of Patient Satisfaction with the Treatment of Acute Venous Thromboembolism with Rivaroxaban or Low Molecular Weight Heparin in Cancer Patients. A Randomized Phase 3 Study) is a prospective, multicenter, randomized, open-label study that evaluated cancer patients reported treatment satisfaction with XARELTO in comparison with standard treatment with low molecular weight heparin in the treatment of VTE.
  • FRONTLINE-2³⁷ (Fundamental Research in Oncology and Thrombosis 2: A Follow Up Survey) is a global survey of physicians’ perceptions and practice in the management of VTE in patients with cancer and approach its prophylaxis and treatment.

Pulmonary Embolism – Early Discharge from the Emergency Room

• MERCURY PE³⁸ (Multicenter Trial of Rivaroxaban for early discharge of Pulmonary Embolism from the Emergency Department) was a randomized, open-label, parallel-group, multicenter, prospective, phase 4 study designed to determine if patients diagnosed with PE and identified as being at low risk of clinical deterioration may be safely discharged from the Emergency Department (ED) and treated with XARELTO as outpatients. The study evaluated whether these patients require fewer hospital days and lower costs compared to those on SOC therapy.
  • Study Design: Upon ED discharge, patients were randomized in a 1:1 ratio to the following treatment arms: XARELTO (15 mg taken twice daily with food for the first 21 days, followed by 20 mg once daily with food for approximately 69 days) or SOC as per local protocol. The primary efficacy outcome was the total amount of time (expressed in hours) spent in the hospital (including the index admission) for VTE or bleeding-related events during the first 30 days following randomization. The primary safety outcome was major bleeding within 90 days.

Embolic Stroke of Undetermined Source

• NAVIGATE ESUS³⁹, was an international, double-blind, randomized, phase 3 study comparing XARELTO 15 mg once daily with aspirin 100 mg once daily for reduction in the risk of recurrent stroke (ischemic, hemorrhagic, and undefined, including TIAs) or systemic embolism in patients with recent embolic stroke. The primary safety outcome was major bleeding according to ISTH criteria.

Following Transcatheter Aortic Valve Replacement (TAVR)

• GALLILEO⁴⁰, (A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement) the Bayer U.S. LLC-sponsored study was a randomized, open label, active-controlled, multicenter phase III trial to evaluate clinical outcomes after successful transcatheter aortic valve replacement (TAVR) in 1644 patients without atrial fibrillation, randomized to either a XARELTO-based anticoagulation strategy or an antiplatelet-based strategy. The first group received XARELTO 10 mg once daily and acetylsalicylic acid (ASA) 75-100 mg once daily for 90 days followed by maintenance with XARELTO 10 mg once daily; whereas the comparator group was given clopidogrel 75 mg and ASA 75-100 mg once daily for 90 days followed by ASA alone. The primary efficacy endpoint is a composite of all-cause death, stroke, systemic embolism, myocardial infarction, pulmonary embolism, deep vein thrombosis, and symptomatic valve thrombosis. The primary safety endpoint is a composite of life-threatening or disabling (BARC types 5 and 3b/3c) and major (BARC type 3a) bleeding events.

Observational Registries

• ORBIT-AF I⁴¹ (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation I) is a prospective, observational disease registry to identify treatment patterns and outcomes of patients with AF. The registry consists of nation-wide collaboration from a variety of HCPs with a focus on outpatient management associated with anticoagulant therapies. The primary outcome is stroke or non-CNS systemic embolism.
• ORBIT-AF II⁴² (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II) is a prospective, observational disease registry to assess the safety and efficacy of target-specific antithrombotic agents including NOACs, Factor Xa inhibitors, direct thrombin inhibitors in patients with AF. The registry will be used to identify treatment patterns and related outcomes. Patients enrolled in the registry will be monitored for up to 2 years.
• GARFIELD AF⁴³ (A Worldwide Prospective Registry of Patients with Atrial Fibrillation at Risk of Stroke) was a prospective, multi-center, international registry of male and female patients newly diagnosed with AF. The study assessed data on patients AF burden, patients’ clinical profile, patterns of clinical practice and antithrombotic management, focusing on stroke/systemic embolism prevention, uptake of new oral anticoagulants and impact on death and bleeding.

Post-Marketing Surveillance Studies

• XAMOS⁴⁴ was an observational parallel-group study that assessed the prophylactic potential of post-surgical VTE following major orthopedic hip or knee surgery. The study documented the effectiveness and safety of XARELTO in comparison with current standards of VTE prophylaxis in 17,701 patients.
• XALIA⁴⁵ (XARELTO for Long-term and Initial Anticoagulation in venous thromboembolism) was a global, prospective, observational study designed to assess the effectiveness and safety of XARELTO as monotherapy for treatment of acute DVT compared with standard therapy.
• XALIA LEA⁴⁶ (XARELTO for Long-term and Initial Anticoagulation in venous thromboembolism) was a global, prospective, observational study designed to assess the effectiveness and safety of XARELTO as monotherapy for treatment of acute DVT compared with standard therapy. This study was conducted in regions not included in XALIA (Latin America, Eastern Europe, the Middle East, Africa, and Asia Pacific).
• XANAP⁴⁷ (A Real-World, Prospective, Observational Study of Patients Treated with Rivaroxaban for Stroke Prevention in Atrial Fibrillation in Asia) was prospective, real-world, observational study in patients with NVAF that evaluated the safety and effectiveness of XARELTO in patients with AF in routine clinical practice in the Asia-Pacific region.  

Risk Reduction of Major Venous and Arterial Thrombotic Events in Patients with COVID-19

• PREVENT-HD⁴⁸ was a multicenter, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of prophylactic XARELTO 10 mg to reduce major venous and arterial thrombotic events, hospitalization, and mortality in outpatients with symptomatic COVID-19 and at least one thrombosis risk factor. The primary efficacy outcome was time to first occurrence of a composite of symptomatic VTE, MI, ischemic stroke, acute limb ischemia, non-central nervous system systemic arterial embolism, all-cause hospitalization, or all-cause mortality through day 35. The principal safety outcome was International Society on Thrombosis and Hemostasis critical-site or fatal bleeding. The study was ended early because of recruitment challenges and lower-than-expected event rate.
  • There was no reduction in the composite end point of venous and arterial thrombotic events, hospitalization, and death in outpatients who were prescribed XARELTO for 35 days.

LITERATURE SEARCH

A literature search of MEDLINE^® EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 03 September 2024.