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Safety and Efficacy of LMWH Versus Rivaroxaban in Chinese Patients Hospitalized With Acute Coronary Syndrome (H-REPLACE)

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ClinicalTrials.gov Identifier: NCT03363035
Recruitment Status : Recruiting
First Posted : December 5, 2017
Last Update Posted : March 17, 2020
Sponsor:
Information provided by (Responsible Party):
Shenghua Zhou, Second Xiangya Hospital of Central South University

Brief Summary:
H-REPLACE trial is a prospective, randomized, open-label, active-controlled, multicenter study in participants with ACS (STEMI or NSTEMI, unstable angina). All eligible participants receiving background treatment of aspirin plus clopidogrel or ticagrelor will be randomly assigned to either oral rivaroxaban 2.5 mg twice daily or rivaroxaban 5 mg twice daily or subcutaneous (SC) enoxaparin 1mg/kg twice daily until hospital discharge or 12 hours before revascularization therapy for a maximum of 8 days.

Condition or disease Intervention/treatment Phase
Acute Coronary Syndrome Myocardial Infarction Myocardial Ischemia Unstable Angina Drug: Rivaroxaban 2.5 mg Drug: Rivaroxaban 5 mg Drug: Enoxaparin Phase 4

Detailed Description:

Acute coronary syndrome (ACS) is a serious and life threatening condition. Anticoagulation during the acute phase of ACS is effective in reducing ischaemic events. The combination regimen of anticoagulation with dual antiplatelet therapy (DAPT) strategy is more effective than either treatment alone. The most widely used parenteral anticoagulation agent in ACS patients is enoxaparin (1 mg/kg administered subcutaneously twice daily).

Rivaroxaban is a novel oral anticoagulant with potent anti-Xa activity, which might be an attractive alternative drug to enoxaparin. In fact, rivaroxaban was consistently shown to be non-inferior to enoxaparin therapy aimed to reduce the event of recurrent venous thromboembolism. Moreover, the bleeding risk of low dose of rivaroxaban is low and acceptable (1.0-2.5%) during the acute phase of ACS as shown by ATLAS ACS-TIMI 46 Trial, and the bleeding risk of enoxaparin during the acute phase of ACS was 4.3% as shown in a meta-analysis.

We thus hypothesized that the safety and efficacy of rivaroxaban during the acute phase of ACS is non-inferior to enoxaparin and designed this prospective, randomized, open-label, active-controlled, multicenter study in participants with ACS (STEMI or NSTEMI or unstable angina). All eligible participants receiving background treatment of aspirin plus clopidogrel or ticagrelor will be randomly assigned to either receive oral rivaroxaban 2.5 mg twice daily or oral rivaroxaban 5 mg twice daily or enoxaparin 1mg/kg twice daily SC until hospital discharge or 12 hours before revascularization therapy for a maximum of 8 days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2055 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Low Molecular Weight Heparin Versus Rivaroxaban in Chinese Patients Hospitalized With Acute Coronary Syndrome(H-REPLACE): a Prospective, Randomized, Open-label, Active-controlled, Multicenter Trial
Actual Study Start Date : January 15, 2018
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Rivaroxaban

Arm Intervention/treatment
Experimental: Rivaroxaban 2.5 mg
One 2.5 mg rivaroxaban tablet twice daily
Drug: Rivaroxaban 2.5 mg
One 2.5 mg rivaroxaban tablet twice daily until hospital discharge or 12 hours before revascularization therapy for a maximum of 8 days.
Other Name: Xarelto

Experimental: Rivaroxaban 5 mg
One 5 mg rivaroxaban tablet twice daily
Drug: Rivaroxaban 5 mg
One 5 mg rivaroxaban tablet twice daily until hospital discharge or 12 hours before revascularization therapy for a maximum of 8 days.
Other Name: Xarelto

Active Comparator: enoxaparin
Enoxaparin 1mg/kg twice daily SC twice daily
Drug: Enoxaparin
Enoxaparin 1mg/kg twice daily SC until hospital discharge or 12 hours before revascularization therapy for a maximum of 8 days.
Other Name: LWMH




Primary Outcome Measures :
  1. Primary Safety Outcome: The percentage of patients with minor, clinically relevant non-major (CRNM) and major bleeding [International Society on Thrombosis and Haemostasis (ISTH) definition of bleeding] [ Time Frame: From the time of randomization (Day 1) up to completion of the follow up phase (Month 6) ]
    The percentage of patients with the first occurrence of bleeding event according to ISTH definition. The statistical analysis was based on the occurrence of the bleeding event from randomization to Month 6.

  2. Primary Efficacy Outcome: The percentage of patients with the composite endpoint of cardiac death, myocardial infarction, re-revascularization or stroke. [ Time Frame: From the time of randomization (Day 1) up to completion of the follow up phase (Month 6). ]
    The percentage of patients with the first occurrence of the composite of death, myocardial infarction, re-revascularization or stroke. The statistical analysis was based on the time from randomization to the first occurrence of the event up to Month 6.


Secondary Outcome Measures :
  1. The percentage of patients with the cardiac-related rehospitalization. [ Time Frame: From the time of randomization (Day 1) up to completion of the follow up phase (Month 6). ]
    The percentage of patients with the cardiac-related rehospitalization. The statistical analysis was based on the time from randomization to the first occurrence of the event up to Month 6.

  2. The percentage of patients with the all-cause death. [ Time Frame: From the time of randomization (Day 1) up to completion of the follow up phase (Month 6). ]
    The percentage of patients with the all-cause death. The statistical analysis was based on the time from randomization to the first occurrence of the event up to Month 6.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female aged ≥ 18 years
  • Diagnosed with ACS (STEMI, NSTEMI, unstable angina)
  • With an indication for short-term combination use of DAPT and enoxaparin.

Exclusion Criteria:

  • Already received thrombolytic therapy or revascularization or needing revascularization therapy in 12 hours.
  • With platelet glycoprotein IIb/IIIa receptor antagonist therapy.
  • With increased bleeding risk, such as but not limited to, active internal bleeding, clinically significant bleeding, bleeding at a non-compressible site, or bleeding diathesis within 30 days of randomization; platelet count less than 90,000/μL at screening; intracranial hemorrhage; major surgery, biopsy of a parenchymal organ, or serious trauma within 30 days before randomization; clinically significant gastrointestinal bleeding within 12 months before randomization; an international normalized ratio known to be>1.5 at the time of screening; abciximab bolus or infusion within the preceding 8 hours, or an eptifibatide or tirofiban bolus or infusion within the past 2 hours preceding randomization; or any other condition known to increase the risk of bleeding.
  • Severe concomitant condition or disease, such as cardiogenic shock at the time of randomization, ventricular arrhythmia refractory to treatment at the time of randomization, calculated creatinine clearance b 30 mL/min at screening, known significant liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis), or liver function test abnormalities (confirmed with repeat testing) which would require study drug discontinuation, i.e., aminoleucine transferase (ALT) >5 × the upper limit of the normal range (ULN) or ALT >3 × ULN plus total bilirubin >2 × ULN, prior ischemic stroke or transient ischemia attack, anemia (i.e., hemoglobin < 10 g/ dL= at screening, known clinical history of human immunodeficiency virus infection at screening, substance abuse (drug or alcohol) problem within the previous 6 months or any severe condition such as cancer that would limit life expectancy to less than 6 months.
  • With an indication for long-term oral anticoagulation therapy such as atrial fibrillation, venous thromboembolism, or prior placement of a mechanical heart valve.
  • With other contraindications for use of rivaroxaban and enoxaparin.
  • Enrolled in another clinical study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03363035


Contacts
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Contact: Shenghua Zhou, Ph.D. +86 0731-85292013 zhoushenghua@csu.edu.cn

Locations
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Sponsors and Collaborators
Second Xiangya Hospital of Central South University
Investigators
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Principal Investigator: Shenghua Zhou, Ph.D. Second Xiangya Hospital of Central South University
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Shenghua Zhou, Professor, Second Xiangya Hospital of Central South University
ClinicalTrials.gov Identifier: NCT03363035    
Other Study ID Numbers: H-REPLACE-201711
First Posted: December 5, 2017    Key Record Dates
Last Update Posted: March 17, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Myocardial Infarction
Acute Coronary Syndrome
Myocardial Ischemia
Angina, Unstable
Syndrome
Infarction
Ischemia
Disease
Pathologic Processes
Necrosis
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Pain
Neurologic Manifestations
Enoxaparin
Rivaroxaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents