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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 : January 17, 2018
Sponsor:
Information provided by (Responsible Party):

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.

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3390 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 : December 31, 2019
Estimated Study Completion Date : May 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Rivaroxaban
U.S. FDA Resources

Arms and Interventions

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


Outcome Measures

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.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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.
Contacts and Locations

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

Locations
China, Hunan
The First People's Hospital of Changde City Not yet recruiting
Changde, Hunan, China, 415003
Contact: Liangqing Ge, Ph.D.    +86 13973652828    geliangqing@163.com   
Changsha Central Hospital Not yet recruiting
Changsha, Hunan, China, 410004
Contact: Luping Jiang, Ph.D.    +86 18374892303    lukejlp@126.com   
Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University Not yet recruiting
Changsha, Hunan, China, 410005
Contact: Zhaofen Zheng, Ph.D.    +86 13974829586    zhaofenz@foxmail.com   
The Forth Hospital of Changsha Not yet recruiting
Changsha, Hunan, China, 410006
Contact: Hao Gong, M.D.    +86 13873182948    949527198@qq.com   
The First Affiliated Hospital of Hunan University of Chinese Medicine Not yet recruiting
Changsha, Hunan, China, 410007
Contact: Yizhi Wu, M.D.    +86 18008485122    yywyz@medmail.com.cn   
The Second Xiangya Hospital of Central South University Recruiting
Changsha, Hunan, China, 410011
Contact: Shenghua Zhou         
The First Hospital of Changsha Not yet recruiting
Changsha, Hunan, China, 410013
Contact: Guang Fu, M.D.    +86 13755170528    fuguangyisheng@163.com   
The Third Xiangya Hospital of Central South University Not yet recruiting
Changsha, Hunan, China, 410013
Contact: Weihong Jiang, Ph.D.    +86 13786113632    jwhxy3@126.com   
The Third Hospital of Changsha Not yet recruiting
Changsha, Hunan, China, 410015
Contact: Yumin Zhang, M.D.    +86 13574145995    20428251@qq.com   
The Second People's Hospital of Hunan Province Not yet recruiting
Changsha, Hunan, China, 430100
Contact: Xiang Liu, M.D.    +86 13975198853    liuxiang_0927@163.com   
The First People's Hospital of Chenzhou Not yet recruiting
Chenzhou, Hunan, China, 423000
Contact: Zhonghua Wang, M.D.    +86 13975521597    105025@sina.com   
The First Affiliated Hospital of University of South China Not yet recruiting
Hengyang, Hunan, China, 421001
Contact: Changhui Liu, Ph.D.    +86 13786435885    liuchanghuidaoshi@163.com   
The Second Affiliated Hospital of University of South China Not yet recruiting
Hengyang, Hunan, China, 421001
Contact: Gaofeng Zeng, Ph.D.    +86 13873418573    2379795177@qq.com   
The First Affiliated Hospital of Hunan University of Medicine Not yet recruiting
Huaihua, Hunan, China, 418000
Contact: Youliang Huang, M.D.    +86 13974501620    1469477867@qq.com   
The First People's Hospital of Huaihua Not yet recruiting
Huaihua, Hunan, China, 418000
Contact: Qiang Shen, M.D.    +86 13974531980    337825375@qq.com   
The First Affiliated Hospital of Jishou University Not yet recruiting
Jishou, Hunan, China, 416000
Contact: Can Zhu, M.D.    +86 13907439435    zc0629@163.com   
The First People's Hospital of Loudi Not yet recruiting
Loudi, Hunan, China, 417000
Contact: Huaqing Tan, M.D.    +86 13607389129    1063543926@qq.com   
The Central Hospital of Shaoyang Not yet recruiting
Shaoyang, Hunan, China, 422000
Contact: Zewei Ouyang, M.D.    +86 13337391467    zwycy4137@126.com   
Xiangtan Central Hospital Not yet recruiting
Xiangtan, Hunan, China, 411413
Contact: He Huang, M.D.    +86 13607327390    hh13607327390@126.com   
Xiangxiang People's Hospital Not yet recruiting
Xianxiang, Hunan, China, 411400
Contact: Chonglun Zhou, M.D.    +86 13975236189    897236609@qq.com   
Yiyang Central Hospital Not yet recruiting
Yiyang, Hunan, China, 413000
Contact: Xianming Wu, M.D.    +86 13973741819    13973741819@163.com   
The First People's Hospital of Yueyang Not yet recruiting
Yueyang, Hunan, China, 414000
Contact: Xiping Xu, M.D.    +86 13807302918    xxps@sina.com   
Zhuzhou Central Hospital Not yet recruiting
Zhuzhou, Hunan, China, 412007
Contact: Fan Ouyang, Ph.D.    +86 13307327791    1641261977@qq.com   
Sponsors and Collaborators
Second Xiangya Hospital of Central South University
Investigators
Principal Investigator: Shenghua Zhou, Ph.D. Second Xiangya Hospital of Central South University
More Information

Responsible Party: Shenghua Zhou, Professor, Second Xiangya Hospital of Central South University
ClinicalTrials.gov Identifier: NCT03363035     History of Changes
Other Study ID Numbers: H-REPLACE-201711
First Posted: December 5, 2017    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Acute Coronary Syndrome
Syndrome
Infarction
Myocardial Infarction
Ischemia
Myocardial Ischemia
Coronary Artery Disease
Angina, Unstable
Disease
Pathologic Processes
Necrosis
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases
Angina Pectoris
Chest Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Rivaroxaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action