Safety and Efficacy of LMWH Versus Rivaroxaban in Chinese Patients Hospitalized With Acute Coronary Syndrome

Myocardial Infarction Clinical Trial

— H-REPLACE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03363035
• Other study ID #: H-REPLACE-201711
• Status: Completed
• Phase: Phase 4
• Start date: January 15, 2018
• Est. completion date: November 30, 2021

Study information

• Verified date: February 2022
• Source: Second Xiangya Hospital of Central South University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2055
• Est. completion date: November 30, 2021
• Est. primary completion date: November 11, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Angina, Unstable
• Infarction
• Ischemia
• Myocardial Infarction
• Myocardial Ischemia
• Syndrome
• Unstable Angina

Intervention

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.
• 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.
• Enoxaparin
Enoxaparin 1mg/kg twice daily SC until hospital discharge or 12 hours before revascularization therapy for a maximum of 8 days.

Locations

Country	Name	City	State
China	The First People's Hospital of Changde City	Changde	Hunan
China	Changsha Central Hospital	Changsha	Hunan
China	Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University	Changsha	Hunan
China	The First Affiliated Hospital of Hunan University of Chinese Medicine	Changsha	Hunan
China	The First Hospital of Changsha	Changsha	Hunan
China	The Forth Hospital of Changsha	Changsha	Hunan
China	The Second People's Hospital of Hunan Province	Changsha	Hunan
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	The Third Hospital of Changsha	Changsha	Hunan
China	The Third Xiangya Hospital of Central South University	Changsha	Hunan
China	The First People's Hospital of Chenzhou	Chenzhou	Hunan
China	The First Affiliated Hospital of University of South China	Hengyang	Hunan
China	The Second Affiliated Hospital of University of South China	Hengyang	Hunan
China	The First Affiliated Hospital of Hunan University of Medicine	Huaihua	Hunan
China	The First People's Hospital of Huaihua	Huaihua	Hunan
China	The First Affiliated Hospital of Jishou University	Jishou	Hunan
China	The First People's Hospital of Loudi	Loudi	Hunan
China	The Central Hospital of Shaoyang	Shaoyang	Hunan
China	Xiangtan Central Hospital	Xiangtan	Hunan
China	Xiangxiang People's Hospital	Xianxiang	Hunan
China	Yiyang Central Hospital	Yiyang	Hunan
China	Yongzhou First People's Hospital	Yongzhou	Hunan
China	The First People's Hospital of Yueyang	Yueyang	Hunan
China	Zhuzhou Central Hospital	Zhuzhou	Hunan

Sponsors (1)

Lead Sponsor	Collaborator
Second Xiangya Hospital of Central South University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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]	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.	From the time of randomization (Day 1) up to completion of the follow up phase (Month 6)
Primary	Primary Efficacy Outcome: The percentage of patients with the composite endpoint of cardiac death, myocardial infarction, re-revascularization or stroke.	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.	From the time of randomization (Day 1) up to completion of the follow up phase (Month 6).
Secondary	The percentage of patients with the cardiac-related rehospitalization.	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.	From the time of randomization (Day 1) up to completion of the follow up phase (Month 6).
Secondary	The percentage of patients with the all-cause death.	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.	From the time of randomization (Day 1) up to completion of the follow up phase (Month 6).