Safety and Efficacy of LMWH Versus Rivaroxaban in Chinese Patients Hospitalized With Acute Coronary Syndrome
H-REPLACE
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
1 other identifier
interventional
2,055
1 country
24
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Jan 2018
Longer than P75 for phase_4
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 29, 2017
CompletedFirst Posted
Study publicly available on registry
December 5, 2017
CompletedStudy Start
First participant enrolled
January 15, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 11, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
November 30, 2021
CompletedFebruary 22, 2022
February 1, 2022
3.8 years
November 29, 2017
February 21, 2022
Conditions
Outcome Measures
Primary Outcomes (2)
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 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 Outcomes (2)
The percentage of patients with the cardiac-related rehospitalization.
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.
From the time of randomization (Day 1) up to completion of the follow up phase (Month 6).
Study Arms (3)
Rivaroxaban 2.5 mg
EXPERIMENTALOne 2.5 mg rivaroxaban tablet twice daily
Rivaroxaban 5 mg
EXPERIMENTALOne 5 mg rivaroxaban tablet twice daily
enoxaparin
ACTIVE COMPARATOREnoxaparin 1mg/kg twice daily SC twice daily
Interventions
One 2.5 mg rivaroxaban tablet twice daily until hospital discharge or 12 hours before revascularization therapy for a maximum of 8 days.
One 5 mg rivaroxaban tablet twice daily until hospital discharge or 12 hours before revascularization therapy for a maximum of 8 days.
Enoxaparin 1mg/kg twice daily SC until hospital discharge or 12 hours before revascularization therapy for a maximum of 8 days.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (24)
The First People's Hospital of Changde City
Changde, Hunan, 415003, China
Changsha Central Hospital
Changsha, Hunan, 410004, China
Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University
Changsha, Hunan, 410005, China
The Forth Hospital of Changsha
Changsha, Hunan, 410006, China
The First Affiliated Hospital of Hunan University of Chinese Medicine
Changsha, Hunan, 410007, China
The Second Xiangya Hospital of Central South University
Changsha, Hunan, 410011, China
The First Hospital of Changsha
Changsha, Hunan, 410013, China
The Third Xiangya Hospital of Central South University
Changsha, Hunan, 410013, China
The Third Hospital of Changsha
Changsha, Hunan, 410015, China
The Second People's Hospital of Hunan Province
Changsha, Hunan, 430100, China
The First People's Hospital of Chenzhou
Chenzhou, Hunan, 423000, China
The First Affiliated Hospital of University of South China
Hengyang, Hunan, 421001, China
The Second Affiliated Hospital of University of South China
Hengyang, Hunan, 421001, China
The First Affiliated Hospital of Hunan University of Medicine
Huaihua, Hunan, 418000, China
The First People's Hospital of Huaihua
Huaihua, Hunan, 418000, China
The First Affiliated Hospital of Jishou University
Jishou, Hunan, 416000, China
The First People's Hospital of Loudi
Loudi, Hunan, 417000, China
The Central Hospital of Shaoyang
Shaoyang, Hunan, 422000, China
Xiangtan Central Hospital
Xiangtan, Hunan, 411413, China
Xiangxiang People's Hospital
Xianxiang, Hunan, 411400, China
Yiyang Central Hospital
Yiyang, Hunan, 413000, China
Yongzhou First People's Hospital
Yongzhou, Hunan, 425000, China
The First People's Hospital of Yueyang
Yueyang, Hunan, 414000, China
Zhuzhou Central Hospital
Zhuzhou, Hunan, 412007, China
Related Publications (3)
Zhang Q, Ding H, Dai Z, Yang R, Zhou S, Tai S. U-shaped association between plasma cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) levels and myocardial infarction. BMC Cardiovasc Disord. 2025 Feb 19;25(1):116. doi: 10.1186/s12872-025-04543-9.
PMID: 39972291DERIVEDZhou S, Xiao Y, Zhou C, Zheng Z, Jiang W, Shen Q, Zhu C, Pan H, Liu C, Zeng G, Ge L, Zhang Y, Ouyang Z, Fu G, Pan G, Chen F, Huang L, Liu Q; H-REPLACE Investigators. Effect of Rivaroxaban vs Enoxaparin on Major Cardiac Adverse Events and Bleeding Risk in the Acute Phase of Acute Coronary Syndrome: The H-REPLACE Randomized Equivalence and Noninferiority Trial. JAMA Netw Open. 2023 Feb 1;6(2):e2255709. doi: 10.1001/jamanetworkopen.2022.55709.
PMID: 36763358DERIVEDXiao 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.
PMID: 32965585DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Shenghua Zhou, Ph.D.
Second Xiangya Hospital of Central South University
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
November 29, 2017
First Posted
December 5, 2017
Study Start
January 15, 2018
Primary Completion
November 11, 2021
Study Completion
November 30, 2021
Last Updated
February 22, 2022
Record last verified: 2022-02
Data Sharing
- IPD Sharing
- Will not share