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

Central South University

Status and phase: Completed; Phase 4

Conditions: Myocardial Ischemia; Unstable Angina; Acute Coronary Syndrome; Myocardial Infarction

Treatments: Drug: Rivaroxaban 5 mg; Drug: Rivaroxaban 2.5 mg; Drug: Enoxaparin

Study type: Interventional

Funder types: Other

Identifiers

NCT03363035

H-REPLACE-201711

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2,055 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,055 participants in 3 patient groups

Rivaroxaban 2.5 mg

Experimental group

Description:

One 2.5 mg rivaroxaban tablet twice daily

Treatment:

Drug: Rivaroxaban 2.5 mg

Rivaroxaban 5 mg

Experimental group

Description:

One 5 mg rivaroxaban tablet twice daily

Treatment:

Drug: Rivaroxaban 5 mg

enoxaparin

Active Comparator group

Description:

Enoxaparin 1mg/kg twice daily SC twice daily

Treatment:

Drug: Enoxaparin