Bivalirudin With Prolonged Full Dose Infusion Versus Heparin Alone During Emergency PCI (BRIGHT-4)

Bivalirudin With Prolonged Full Dose Infusion Versus Heparin Alone During: a Multicenter, Randomized, Open-label Trial

This study is aimed to investigate if the bivaliruding with prolonged full dose infusion after PCI is superior to heparin alone in reducing 30-day mortality or major bleeding for patients with STEMI treated with emergency PCI. A total of 6000 STEMI patients will be enrolled and randomly assigned to receive bivalirudin or heparin during emergency PCI in a 1:1 ratio. This study will provide key evidence for peri-operative anticoagulant therapy decisions in STEMI patients.

Study Overview

• Status: Active, not recruiting
• Conditions: ST Elevation Myocardial Infarction
• Intervention / Treatment: Drug: Bivalirudin; Drug: unfractionated Heparin

• Study Type: Interventional
• Enrollment (Actual): 6016
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China
      • Bengbu Second People's Hospital
    • Fuyang, Anhui, China
      • Fu Yang People's Hospital
    • Fuyang, Anhui, China
      • Linquan County Peoples Hospital
    • Fuyang, Anhui, China
      • No.2 People's Hospital of Fuyang City
    • Fuyang, Anhui, China
      • Taihe County People'S Hospital
    • Haozhou, Anhui, China
      • Bozhou Peoples Hospital
    • Huainan, Anhui, China
      • Huainan Oriental Hospital Group Affiliated Hospital of Anhui University of Science & Technology
    • Huainan, Anhui, China
      • The First Hospital of Anhui University of Science&Technology
    • Suzhou, Anhui, China
      • Suzhou Municipal Hospital
  • Beijing
    • Beijing, Beijing, China
      • Beijing Luhe Hospital.Capital Medical University
    • Beijing, Beijing, China
      • Peking University Third Hospital YanQing Hospital
  • Chongqing
    • Chongqing, Chongqing, China
      • Chongqing University Fuling Hospital
  • Gansu
    • Lanzhou, Gansu, China
      • The First Hospital of Lanzhou University
  • Guangdong
    • Meizhou, Guangdong, China
      • Meizhou Peopie's Hospital
  • Guangxi
    • Yulin, Guangxi, China
      • Yulin First People's Hospital
  • Guizhou
    • Guiyang, Guizhou, China
      • The Affiliated Hospital of Guizhou Medical University
    • Zunyi, Guizhou, China
      • Affiliated Hospital Ofzunyi Medical University
  • Hebei
    • Hengshui, Hebei, China
      • Hengshuicardiovascularhospital
  • Henan
    • Jiaozuo, Henan, China
      • Jiaozuo People's Hospital
    • Kaifeng, Henan, China
      • Kaifeng Central Hospital
    • Luohe, Henan, China
      • Luohe Central Hospital
    • Ruzhou, Henan, China
      • The First People'S Hospital of Ruzhou
    • Shangqiu, Henan, China
      • Shangqiu First People's Hospital
    • Xinxiang, Henan, China
      • The Third Affiliated Hospital of Xinxiang Medical University
    • Yuzhou, Henan, China
      • Yuzhoucitypeopleshospital
    • Zhengzhou, Henan, China
      • Fuwai Central China Cardiovascular Hospital
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University Center 1
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University Center 2
    • Zhengzhou, Henan, China
      • The First People's Hospital of Xinmi
  • Hubei
    • Wuhan, Hubei, China
      • Itchoshtal Tonjinee Colere Hoatono Innehatyor Seene Ano Thohholdcy
    • Wuhan, Hubei, China
      • Tongji Hospital Tongji Medical College of HUST
    • Wuhan, Hubei, China
      • Wuhanasia Heart Hospital
  • Hunan
    • Loudi, Hunan, China
      • Lou Di Central Hospital
    • Xiangtan, Hunan, China
      • Xiangtan Central Hospital
    • Yueyang, Hunan, China
      • Yueyang Central Hospital
  • Inner Mongolia
    • Chifeng, Inner Mongolia, China
      • Chifeng College Affiliated Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Nanjing Firsthospital
    • Taizhou, Jiangsu, China
      • Jiangsutaizhou Peoples Hospital
    • Xuzhou, Jiangsu, China
      • XuZhou Central Hospital
  • Jiangxi
    • Ganzhou, Jiangxi, China
      • First Affiliated hospital of GANNAN Medical University
    • Ganzhou, Jiangxi, China
      • Ganzhou Municipal Hospital
    • Ganzhou, Jiangxi, China
      • Nan Fang Hospital.Ganzhou
    • Nanchang, Jiangxi, China
      • The Second Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China
      • The Jiangxi Provincial People's Hospital
    • Nanchang, Jiangxi, China
      • Thefirstaffiliated Hospitalofnanchang University
  • Jilin
    • Chang chun, Jilin, China
      • China-Japan Union Hospital of Jilin University
    • Chang chun, Jilin, China
      • The Second Hospital of Jilin University
    • Yanbian, Jilin, China
      • Yanbian University Hospital
  • Liaoning
    • Benxi, Liaoning, China
      • General Hospital of Benxi Iron & Steel Industry Group of Liaoning Health Industry Group
    • Dalian, Liaoning, China
      • Dalian No.3 People'S Hospital
    • Diaobingshan, Liaoning, China
      • Jiangpiqiao99@sina.com
    • Fushun, Liaoning, China
      • Fushun central hospital
    • Fushun, Liaoning, China
      • General Hospital of Fushun Mining Industry Group of Liaoning Health Industry Group
    • Fuxin, Liaoning, China
      • General Hospital of Fuxin Mining Industry Group of Liaoning Health Industry Group
    • Shenyang, Liaoning, China
      • the Fourth Affiliated Hospital of China Medical University
    • Shenyang, Liaoning, China
      • General Hospital of Northern Theater Command
    • Shenyang, Liaoning, China
      • The Second Hospital of Shen Yang Medical College
  • Shandong
    • Heze, Shandong, China
      • Heze Municipal Hospital
    • Heze, Shandong, China
      • Heze Mudan People's Hospital
    • Jinan, Shandong, China
      • Jinan Central Hospital
    • Jinan, Shandong, China
      • Shandong Scend Provincial General Hosptial
    • Jinan, Shandong, China
      • The Fifth People's Hospital of Jinan
    • Qingdao, Shandong, China
      • QingDao Municipal Hospital
    • Tai'an, Shandong, China
      • Taian City Central Hospital
    • Xintai, Shandong, China
      • The People's Hospital ofXin Tai City
    • Zaozhuang, Shandong, China
      • Zao Zhuang Central Hospital Of Shandong Guoxin Healthcare Group
  • Shanxi
    • Datong, Shanxi, China
      • Datong Third People'S Hospiatl
    • Taiyuan, Shanxi, China
      • Shanxi Cardiovascular Hospital
    • Xi'an, Shanxi, China
      • Department of Cardiology, Tangdu Hospital, Airforce Medical University
    • Xi'an, Shanxi, China
      • The Amliated HospitalofNorthwest University Xi'an No.3 Hospital
    • Xi'an, Shanxi, China
      • The Second Affiliated Hospital of Xian Jiaotong University
    • Yanan, Shanxi, China
      • Yan 'an University Affiliated Hospital
  • Sichaun
    • Xichang, Sichaun, China
      • The First Hospital of Liangshan
  • Sichuan
    • Bazhong, Sichuan, China
      • The People's Hospital Of Pingchang
    • Chengdu, Sichuan, China
      • ChengDu Second People's Hospital
    • Chengdu, Sichuan, China
      • "West China Hospital Sichuan University"
    • Chengdu, Sichuan, China
      • Hospital of Chengdu University of TCM
    • Luzhou, Sichuan, China
      • The Affiliated Traditional Chinese Medicine Hospital Of Southwest Medical University
    • Xichang, Sichuan, China
      • Xi Chang People'S Hospital
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University General Hospital
    • Tianjin, Tianjin, China
      • Tianjin Chest Hospital
  • Xinjiang
    • Ürümqi, Xinjiang, China
      • The Fifth Affiliated Hospital of Xinjiang Medical University
  • Yunnan
    • Kunming, Yunnan, China
      • Yunnan St.John'S Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Provincial Hospital of Chinese Medicine
    • Taizhou, Zhejiang, China
      • Taizhou Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Any age;
• STEMI patients undergoing primary PCI with ST elevation≥1mm in≥2 contiguous leads or new LBBB with symptom onset 48h;
• Patients requiring staged revascularization of non-culprit vessels within 30 days may be enrolled. In such cases the same antithrombotic agents and PCI procedures must be used in the staged procedure consistent with the index procedure PCI, in particular the assigned antithrombin agent heparin vs. bivalirudin);
• Dual antiplatelet drugs must be administrated according to guidelines before PCI (loading doses and maintenance doses of aspirin and clopidogrel or ticagrelor);
• The subject or legal representative has been informed of the nature of the study, understood the provisions of the protocol, was able to ensure adherence, and signed informed consent.

Exclusion Criteria:

• Not suitable for emergency primary PCI;
• STEMI treated by thrombolysis;
• Patients received heparin, LMWH, fondaparinux, bivalirudin, or GPI within 48 hours before the index PCI;
• Mechanical complications (such as ventricular septal rupture, papillary muscle rupture with acute mitral regurgitation, etc.);
• Known allergy or contraindications to heparin, bivalirudin, aspirin, or both clopidogrel and ticagrelor
• Patients in whom the investigators consider inappropriate to participate in this study (eg, have participated in another drug/instrument study or undergoing another drug/instrument study).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Bivalirudin; Bivalirudin with prolonged full dose infusion during primary PCI	Drug: Bivalirudin; Bivaliruding 0.75 mg/kg intravenous bolus loading dose, and immediately followed by intravenous infusion of 1.75 mg/kg/h until 2-4 hours after PCI. It is recommended that ACT be monitored 5 minutes after the first administration, and if ACT is <225 s (Hemotec method), intravenous injection of 0.35 mg/kg of bivalirudin should be administered, and the ACT re-checked to ensure it is >225 seconds.
ACTIVE_COMPARATOR: Heparin; Heparin alone during primary PCI	Drug: unfractionated Heparin; Heparin 70 U/kg is started before coronary angiography. ACT is monitored 5 min after the first administration, and if the ACT <225 s (Hemotec method), an intravenous injection of 1000 U of heparin is administered, and the ACT re-checked to ensure it is >225 seconds.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of all-cause death or BARC type 3~5 bleeding	BARC=Bleeding academic research consortium	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause mortality		30 days
BARC type 3-5 bleeding	BARC=Bleeding academic research consortium	30 days
Major adverse cardiac and cerebral events (MACE)	MACE is defined as a composite of all cause death, recurrent myocardial infarction, stroke or ischemic driven target vessel revascuarlization	30 days
Net adverse clinical events (NACE)	NACE is defined as a composite of MACE or BARC type 3-5 bleeding	30 days
Composite of all-cause death or BARC type 2-5 bleeding	BARC=Bleeding academic research consortium	30 days
BARC type 2-5 bleeding	BARC=Bleeding academic research consortium	30 days
Stent thrombosis	Definite or probable stent thrombosis according to Academic Research Consortium	30 days
Thrombocytopenia	defined as platelet counts less than 150*10^9/L after treatment	30 days
All cause mortality		1 years

Collaborators and Investigators

• Sponsor: Shenyang Northern Hospital
• Investigators: Principal Investigator: Yaling Han, MD, The General Hospital of Northern Theater Command

Publications and helpful links

General Publications

• Li Y, Liang Z, Qin L, Wang M, Wang X, Zhang H, Liu Y, Li Y, Jia Z, Liu L, Zhang H, Luo J, Dong S, Guo J, Zhu H, Li S, Zheng H, Liu L, Wu Y, Zhong Y, Qiu M, Han Y, Stone GW. Bivalirudin plus a high-dose infusion versus heparin monotherapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomised trial. Lancet. 2022 Nov 26;400(10366):1847-1857. doi: 10.1016/S0140-6736(22)01999-7. Epub 2022 Nov 6.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 14, 2019
• Primary Completion (ACTUAL): May 7, 2022
• Study Completion (ANTICIPATED): May 6, 2023

Study Registration Dates

• First Submitted: January 29, 2019
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (ACTUAL): January 30, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 13, 2022
• Last Update Submitted That Met QC Criteria: June 9, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: heparin; bivalirudin; anticoagulant agents; Primary percutaneous coronary intervention
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Heparin; Bivalirudin; Calcium heparin
• Other Study ID Numbers: 2018-031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No