Clinical trial NCT03363035: Safety and Efficacy of LMWH Versus Rivaroxaban in Chinese Patients Hospitalized With Acute Coronary Syndrome
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Myocardial Infarction
Myocardial Ischemia
Unstable Angina
Lead sponsor: Second Xiangya Hospital of Central South University
Sponsor class: OTHER
First posted: 2017-12-05
Enrollment: 2055
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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]
timeFrame: From the time of randomization (Day 1) up to completion of the follow up phase (Month 6)
measure: Primary Efficacy Outcome: The percentage of patients with the composite endpoint of cardiac death, myocardial infarction, re-revascularization or stroke.
timeFrame: From the time of randomization (Day 1) up to completion of the follow up phase (Month 6).
Secondary outcomes:
measure: The percentage of patients with the cardiac-related rehospitalization.
timeFrame: From the time of randomization (Day 1) up to completion of the follow up phase (Month 6).
measure: The percentage of patients with the all-cause death.
timeFrame: From the time of randomization (Day 1) up to completion of the follow up phase (Month 6).
Other outcomes:
Locations:
city: Changde
country: China
facility: The First People's Hospital of Changde City
state: Hunan
city: Changsha
country: China
facility: Changsha Central Hospital
state: Hunan
city: Changsha
country: China
facility: Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University
state: Hunan
city: Changsha
country: China
facility: The Forth Hospital of Changsha
state: Hunan
city: Changsha
country: China
facility: The First Affiliated Hospital of Hunan University of Chinese Medicine
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: The First Hospital of Changsha
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: The Third Hospital of Changsha
state: Hunan
city: Changsha
country: China
facility: The Second People's Hospital of Hunan Province
state: Hunan
city: Chenzhou
country: China
facility: The First People's Hospital of Chenzhou
state: Hunan
city: Hengyang
country: China
facility: The First Affiliated Hospital of University of South China
state: Hunan
city: Hengyang
country: China
facility: The Second Affiliated Hospital of University of South China
state: Hunan
city: Huaihua
country: China
facility: The First Affiliated Hospital of Hunan University of Medicine
state: Hunan
city: Huaihua
country: China
facility: The First People's Hospital of Huaihua
state: Hunan
city: Jishou
country: China
facility: The First Affiliated Hospital of Jishou University
state: Hunan
city: Loudi
country: China
facility: The First People's Hospital of Loudi
state: Hunan
city: Shaoyang
country: China
facility: The Central Hospital of Shaoyang
state: Hunan
city: Xiangtan
country: China
facility: Xiangtan Central Hospital
state: Hunan
city: Xianxiang
country: China
facility: Xiangxiang People's Hospital
state: Hunan
city: Yiyang
country: China
facility: Yiyang Central Hospital
state: Hunan
city: Yongzhou
country: China
facility: Yongzhou First People's Hospital
state: Hunan
city: Yueyang
country: China
facility: The First People's Hospital of Yueyang
state: Hunan
city: Zhuzhou
country: China
facility: Zhuzhou Central Hospital
state: Hunan
Study officials:
affiliation: Second Xiangya Hospital of Central South University
name: Shenghua Zhou, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.