Back to resultsSafety and Efficacy of LMWH Versus Rivaroxaban in Chinese Patients Hospitalized With Acute Coronary Syndrome (H-REPLACE)
Primary Purpose
Acute Coronary Syndrome, Myocardial Infarction, Myocardial Ischemia
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Rivaroxaban 2.5 mg
Rivaroxaban 5 mg
Enoxaparin
Sponsored by
About this trial
This is an interventional treatment trial for Acute Coronary Syndrome
Eligibility 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.
Sites / Locations
- The First People's Hospital of Changde City
- Changsha Central Hospital
- Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University
- The Forth Hospital of Changsha
- The First Affiliated Hospital of Hunan University of Chinese Medicine
- The Second Xiangya Hospital of Central South University
- The First Hospital of Changsha
- The Third Xiangya Hospital of Central South University
- The Third Hospital of Changsha
- The Second People's Hospital of Hunan Province
- The First People's Hospital of Chenzhou
- The First Affiliated Hospital of University of South China
- The Second Affiliated Hospital of University of South China
- The First Affiliated Hospital of Hunan University of Medicine
- The First People's Hospital of Huaihua
- The First Affiliated Hospital of Jishou University
- The First People's Hospital of Loudi
- The Central Hospital of Shaoyang
- Xiangtan Central Hospital
- Xiangxiang People's Hospital
- Yiyang Central Hospital
- Yongzhou First People's Hospital
- The First People's Hospital of Yueyang
- Zhuzhou Central Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Rivaroxaban 2.5 mg
Rivaroxaban 5 mg
enoxaparin
Arm Description
One 2.5 mg rivaroxaban tablet twice daily
One 5 mg rivaroxaban tablet twice daily
Enoxaparin 1mg/kg twice daily SC twice daily
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT03363035
First Posted
November 29, 2017
Last Updated
February 21, 2022
Sponsor
Second Xiangya Hospital of Central South University
1. Study Identification
Unique Protocol Identification Number
NCT03363035
Brief Title
Safety and Efficacy of LMWH Versus Rivaroxaban in Chinese Patients Hospitalized With Acute Coronary Syndrome
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
January 15, 2018 (Actual)
Primary Completion Date
November 11, 2021 (Actual)
Study Completion Date
November 30, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Second Xiangya Hospital of Central South University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Coronary Syndrome, Myocardial Infarction, Myocardial Ischemia, Unstable Angina
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2055 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rivaroxaban 2.5 mg
Arm Type
Experimental
Arm Description
One 2.5 mg rivaroxaban tablet twice daily
Arm Title
Rivaroxaban 5 mg
Arm Type
Experimental
Arm Description
One 5 mg rivaroxaban tablet twice daily
Arm Title
enoxaparin
Arm Type
Active Comparator
Arm Description
Enoxaparin 1mg/kg twice daily SC twice daily
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban 2.5 mg
Other Intervention Name(s)
Xarelto
Intervention Description
One 2.5 mg rivaroxaban tablet twice daily until hospital discharge or 12 hours before revascularization therapy for a maximum of 8 days.
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban 5 mg
Other Intervention Name(s)
Xarelto
Intervention Description
One 5 mg rivaroxaban tablet twice daily until hospital discharge or 12 hours before revascularization therapy for a maximum of 8 days.
Intervention Type
Drug
Intervention Name(s)
Enoxaparin
Other Intervention Name(s)
LWMH
Intervention Description
Enoxaparin 1mg/kg twice daily SC until hospital discharge or 12 hours before revascularization therapy for a maximum of 8 days.
Primary Outcome Measure Information:
Title
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]
Description
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.
Time Frame
From the time of randomization (Day 1) up to completion of the follow up phase (Month 6)
Title
Primary Efficacy Outcome: The percentage of patients with the composite endpoint of cardiac death, myocardial infarction, re-revascularization or stroke.
Description
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.
Time Frame
From the time of randomization (Day 1) up to completion of the follow up phase (Month 6).
Secondary Outcome Measure Information:
Title
The percentage of patients with the cardiac-related rehospitalization.
Description
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.
Time Frame
From the time of randomization (Day 1) up to completion of the follow up phase (Month 6).
Title
The percentage of patients with the all-cause death.
Description
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.
Time Frame
From the time of randomization (Day 1) up to completion of the follow up phase (Month 6).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shenghua Zhou, Ph.D.
Organizational Affiliation
Second Xiangya Hospital of Central South University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First People's Hospital of Changde City
City
Changde
State/Province
Hunan
ZIP/Postal Code
415003
Country
China
Facility Name
Changsha Central Hospital
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410004
Country
China
Facility Name
Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410005
Country
China
Facility Name
The Forth Hospital of Changsha
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410006
Country
China
Facility Name
The First Affiliated Hospital of Hunan University of Chinese Medicine
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410007
Country
China
Facility Name
The Second Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410011
Country
China
Facility Name
The First Hospital of Changsha
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
Facility Name
The Third Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
Facility Name
The Third Hospital of Changsha
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410015
Country
China
Facility Name
The Second People's Hospital of Hunan Province
City
Changsha
State/Province
Hunan
ZIP/Postal Code
430100
Country
China
Facility Name
The First People's Hospital of Chenzhou
City
Chenzhou
State/Province
Hunan
ZIP/Postal Code
423000
Country
China
Facility Name
The First Affiliated Hospital of University of South China
City
Hengyang
State/Province
Hunan
ZIP/Postal Code
421001
Country
China
Facility Name
The Second Affiliated Hospital of University of South China
City
Hengyang
State/Province
Hunan
ZIP/Postal Code
421001
Country
China
Facility Name
The First Affiliated Hospital of Hunan University of Medicine
City
Huaihua
State/Province
Hunan
ZIP/Postal Code
418000
Country
China
Facility Name
The First People's Hospital of Huaihua
City
Huaihua
State/Province
Hunan
ZIP/Postal Code
418000
Country
China
Facility Name
The First Affiliated Hospital of Jishou University
City
Jishou
State/Province
Hunan
ZIP/Postal Code
416000
Country
China
Facility Name
The First People's Hospital of Loudi
City
Loudi
State/Province
Hunan
ZIP/Postal Code
417000
Country
China
Facility Name
The Central Hospital of Shaoyang
City
Shaoyang
State/Province
Hunan
ZIP/Postal Code
422000
Country
China
Facility Name
Xiangtan Central Hospital
City
Xiangtan
State/Province
Hunan
ZIP/Postal Code
411413
Country
China
Facility Name
Xiangxiang People's Hospital
City
Xianxiang
State/Province
Hunan
ZIP/Postal Code
411400
Country
China
Facility Name
Yiyang Central Hospital
City
Yiyang
State/Province
Hunan
ZIP/Postal Code
413000
Country
China
Facility Name
Yongzhou First People's Hospital
City
Yongzhou
State/Province
Hunan
ZIP/Postal Code
425000
Country
China
Facility Name
The First People's Hospital of Yueyang
City
Yueyang
State/Province
Hunan
ZIP/Postal Code
414000
Country
China
Facility Name
Zhuzhou Central Hospital
City
Zhuzhou
State/Province
Hunan
ZIP/Postal Code
412007
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32965585
Citation
Xiao Y, Tang L, Liu Q, Hu X, Fang Z, Zhou S. Rationale and Design of the H-REPLACE Study: Safety and Efficacy of LMWH Versus Rivaroxaban in ChinEse Patients HospitaLized with Acute Coronary SyndromE. Cardiovasc Drugs Ther. 2022 Feb;36(1):69-73. doi: 10.1007/s10557-020-07076-9. Epub 2020 Sep 23.
Results Reference
derived
Learn more about this trial
Safety and Efficacy of LMWH Versus Rivaroxaban in Chinese Patients Hospitalized With Acute Coronary Syndrome
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