BivaliRudin in Acute Myocardial Infarction vs Glycoprotein IIb/IIIa and Heparin :a Randomised Controlled Trial. (BRIGHT)

Bivalirudin in Acute Myocardial Infarction vs Glycoprotein IIb/IIIa and Heparin Undergoing Angioplasty (BRIGHT):a Randomised Controlled Trial

The study would enrolled a total of 2100 AMI patients undergoing PCI to one of three antithrombotic regimens: bivalirudin alone, or unfractionated heparin alone, or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor.

All enrolled patients would be followed-up to 30 days, 6 months, and 1 year. The purpose of the study is to evaluate the efficacy and safety of bivalirudin in AMI patients with DES.

Study Overview

• Status: Completed
• Conditions: Percutaneous Coronary Intervention; Acute Myocardial Infarction
• Intervention / Treatment: Drug: Bivalirudin; Drug: heparin; Drug: heparin plus tirofiban

Detailed Description

This is a prospective, randomized, single-blind, active drug controlled multicenter clinical research and the study would enrolled a total of 2100 AMI patients undergoing percutaneous coronary intervention (PCI) to one of three antithrombotic regimens: bivalirudin alone, or unfractionated heparin alone, or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor. All enrolled patients would be followed-up to 30 days, 6 months, and 1 year. The purpose of the study is to evaluate the efficacy and safety of bivalirudin in AMI patients with DES.

• Study Type: Interventional
• Enrollment (Actual): 2194
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • 1 st Hosp. of Anhui Med Univ.
    • Hefei, Anhui, China, 230000
      • Anhui Provincial Hosp.
  • Beijing
    • Beijing, Beijing, China, 100000
      • 3rd Hosp. of Beijing Univ.
    • Beijing, Beijing, China, 100000
      • Beijing Anzhen Hosp.
    • Beijing, Beijing, China, 100000
      • Beijing CAPF General Hosp.
    • Beijing, Beijing, China, 100000
      • Beijing Chaoyang Hosp.
    • Beijing, Beijing, China, 100000
      • Beijing Friendship Hosp.
    • Beijing, Beijing, China, 100000
      • Beijing General Hosp. of PLA
    • Beijing, Beijing, China, 100000
      • Beijing Hosp.
    • Beijing, Beijing, China, 100000
      • Beijing Luhe Hosp.
    • Beijing, Beijing, China, 100000
      • General Hosp of PLA (1)
    • Beijing, Beijing, China, 100000
      • General Hosp. of PLA(2)
    • Beijing, Beijing, China, 100000
      • Navy General Hosp. of PLA
    • Beijing, Beijing, China, 100000
      • No.304 Hosp. of PLA
    • Beijing, Beijing, China, 100000
      • No.306 Hosp. of PLA
    • Beijing, Beijing, China, 100000
      • Peking Univ. First Hosp.
    • Beijing, Beijing, China, 100000
      • The 2nd artillery general Hosp. of PLA
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Chongqing Daping Hosp.
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Fujian Med Univ. Uion Hosp.
  • Gansu
    • Lanzhou, Gansu, China, 730030
      • 1 st Hosp. of Lanzhou Univ.
    • Lanzhou, Gansu, China, 730030
      • Lanzhou General Hosp. of PLA
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • 1 st Hosp. of Guangzhou MU
    • Guangzhou, Guangdong, China, 510000
      • 1st Hosp. of Zhongshan MU
    • Guangzhou, Guangdong, China, 510000
      • Guangdong General Hosp.
    • Guangzhou, Guangdong, China, 510000
      • Guangzhou General Hosp. of PLA
  • Guangxi
    • Nanning, Guangxi, China, 210000
      • 1 st Hosp. of Guangxi Med Univ.
  • Hebei
    • Baoding, Hebei, China, 071000
      • No.252 Hosp. of PLA
    • Cangzhou, Hebei, China, 061000
      • Cangzhou Centeral Hosp.
    • Qinhuangdao, Hebei, China, 050000
      • Qinhuangdao No.1 Hosp.
    • Shijiazhuang, Hebei, China, 050000
      • Hebei General Hosp.
    • Shijiazhuang, Hebei, China, 050000
      • Shijiazhuang Peace Hosp.
    • Tangshan, Hebei, China, 063000
      • Tangshan Gongren Hosp.
  • Heilongjiang
    • Daqing, Heilongjiang, China, 150000
      • Daqing General Hosp. of OF.
  • Henan
    • Pingdingshan, Henan, China, 467000
      • No.152 Hosp.
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Wuhan Asican Heart Hosp.
    • Wuhan, Hubei, China, 430000
      • Wuhan General Hosp of PLA
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Nanjing First Hosp.
    • Xuzhou, Jiangsu, China, 221000
      • Xuzhou Med Col. Affiliated Hosp.
    • Xuzhou, Jiangsu, China, 221000
      • Xuzhou No.4 Hosp.
  • Jiangxi
    • Nanchang, Jiangxi, China, 330000
      • 2 nd Hosp. of Nanchang Univ.
  • Jilin
    • Changchun, Jilin, China, 130000
      • 1st Hosp of Jilin Univ.
    • Changchun, Jilin, China, 130000
      • 2nd Hosp of Jilin Univ.
    • Changchun, Jilin, China, 130000
      • 3rd Hosp of Jilin Univ.
    • Meihekou, Jilin, China, 135000
      • Meihekou Central Hosp.
  • Liaoning
    • Dalian, Liaoning, China, 116000
      • Dalian Zhongshan Hosp.
    • Dalian, Liaoning, China, 116000
      • No.210 Hosp of PLA
    • Huludao, Liaoning, China, 125000
      • No.313 Hosp. of PLA
    • Jinzhou, Liaoning, China, 121000
      • 1st Hosp. of Liaoning MC
    • Jinzhou, Liaoning, China, 121000
      • 3 rd Hosp. of Liaoning Med Col.
    • Shenyang, Liaoning, China, 110000
      • No.463 Hosp of PLA
    • Shenyang, Liaoning, China, 110000
      • Shenzhou Hosp. of SMC
    • Yingkou, Liaoning, China, 115000
      • Yingkou Centeral Hosp.
  • Ningxia
    • Yinchuan, Ningxia, China, 750000
      • General Hosp. of Ningxia MU
  • Shandong
    • Ji'nan, Shandong, China, 250000
      • Ji'nan General Hosp. of PLA
    • Jining, Shandong, China, 272000
      • Affiliated Hosp. of Jining MC
    • Taian, Shandong, China, 271000
      • Taian Central Hosp.
    • Yantai, Shandong, China, 261400
      • Yantaishan Hosp.
    • Zibo, Shandong, China, 255000
      • No. 148 Hosp.
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Huashan Hosp.
    • Shanghai, Shanghai, China, 200000
      • Shanghai jingan people's hosp.
    • Shanghai, Shanghai, China, 200000
      • Shanghai Renji Hosp.
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • 1st Hosp. of Shanxi Med Univ.
    • Taiyuan, Shanxi, China, 030000
      • Shanxi Cardiovascular Hosp.
    • Taiyuan, Shanxi, China, 030000
      • Taiyuan Central Hosp.
    • Xi'an, Shanxi, China, 710000
      • 2 nd Hosp. of Xi'an Med Col.
    • Xi'an, Shanxi, China, 710000
      • Shanxi General Hosp. of CAPF
    • Xi'an, Shanxi, China, 710000
      • Shanxi General Hosp.
    • Xi'an, Shanxi, China, 710000
      • Tangdu Hosp.
    • Xi'an, Shanxi, China, 710000
      • Xijing Hosp.
    • Yanan, Shanxi, China, 716000
      • Yanan Univ. affiliated Hosp.
    • Yuncheng, Shanxi, China, 044000
      • Yuncheng Central Hosp.
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Chengdu General Hosp. of PLA
    • Chengdu, Sichuan, China, 610000
      • Chengdu No.2 Hosp.
  • Tianjin
    • Tianjin, Tianjin, China, 300000
      • No.254 Hosp. of PLA
    • Tianjin, Tianjin, China, 300000
      • Tianjin CAPF Hosp.
    • Tianjin, Tianjin, China, 300000
      • Tianjin Chest Hosp.
    • Tianjin, Tianjin, China, 300000
      • Tianjin No.3 Hosp.
    • Tianjin, Tianjin, China, 300000
      • Tianjin People's Hosp.
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • Kunming General Hosp. of PLA
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • 2nd Hosp. of Zhejiang Univ.
    • Hangzhou, Zhejiang, China, 310000
      • Zhejiang Hosp.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 to 80 years old
2. Planned emergency PCI for acute myocardial infarction (STEMI or NSTEMI) Symptom onset within 12h for STEMI (or within 24 h for patients have unrelieved chest pain, continuous ST elevation or new developed LBBB) Symptom onset within 72h for NSTEMI
3. Avoid to undergoing revascularization for non-culprit vessels within 30 days after index procedure.
4. Provide written informed consent.

Exclusion Criteria:

1. Unsuitable for PCI; treatment by thrombolysis within 72 hours of acute ST-elevation myocardial infarction; left main coronary artery disease; cardiogenic shock.
2. Any anticoagulant agents were used 48 h before randomization.
3. Active bleeding or bleeding constitution, bleeding tendency, including the recent retina or vitreous hemorrhage (1 months), GI or urinary tract hemorrhage (3 months), cerebral hemorrhage (6 months) or cerebral infarction history (3 months), etc.;
4. Other disease may lead to vascular lesions and secondary bleeding factors (such as active gastric ulcer, active ulcerative colitis, intracranial aneurysm, etc.),
5. Deep puncture or major surgery (including eye or brain surgery) within 1 month.
6. Suspicious aortic dissection, pericarditis and subacute bacterial endocarditis.
7. Untreated or uncontrolled hypertension > 180/110 mmHg.
8. Hemoglobin < 100 g/L or platelet count < 100 * 109 / L.
9. Elevated AST, ALT level higher than three times of the normal upper limit.
10. severe renal insufficiency (eGFR < 30 mL/min / 1.73 m2).
11. Heparin induced thrombocytopenia.
12. Known allergy to the study drugs and instruments (UFH, bivalirudin, aspirin and clopidogrel, stainless steel, contrast agents, etc.), or those allergic constitution.
13. Pregnancy or lactation.
14. Researchers think that doesn't fit to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bivalirudin; Bivalirudin will be started in the cath lab, 0.75 mg/kg intravenous bolus followed by 1.75 mg/kg per h infusion; if ACT<225s 5min after bolus, an additional dose of 0.3mg/kg bolus should be given. After procedure, a prolonged infusion (1.75mg/kg per h) will be given for at least 30 min (totally no more than 4 h) followed by a reduced dose infusion (0.2mg/kg per h) up to 20 h.	Drug: Bivalirudin; Patients would be given anticoagulant therapy with bivalirudin in acute myocardial infarction during emergency PCI operation.; Other Names: Taijianing
Active Comparator: Heparin monotherapy; 100 IU/kg intravenous bolus. If ACT <225s 5 min after bolus injection, additional dose of heparin (20U/kg) will be given.	Drug: heparin; heparin monotherapy
Active Comparator: heparin plus tirofiban; heparin 60 IU/kg intravenous bolus and Tirofiban: 10μg/kg intravenous bolus followed by 0.15μg/kg per min infusion for up to 36h.	Drug: heparin; heparin monotherapy; Drug: heparin plus tirofiban; combined use of heparin and tirofiban during PCI; Other Names: brand name of tirofiban: Xinweining

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net Adverse Clinical Events	A composite of all cause death, reinfarction, urgent target vessel revascularization, stroke and any bleedings	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net adverse clinical events	a composite of all cause death, any myocardial infarction, any target vessel revascularization, stroke or any bleedings	1 year
Major adverse cardiac and cerebral events (MACCE)	a composite of all cause death, reinfarction, target vessel revascularization or stroke	30 days and 1 year
any bleedings (BARC class)	including all BARC class (class 1-5)	30 day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
stent thrombosis	by ARC definition	30 days and 1 year
Thrombocytopenia	Defined as a decrease of platelet count of more than 50% or more than 150000 platelet/mm3 compared with baseline within 24h after study drug administration	30 days

Collaborators and Investigators

• Sponsor: Shenyang Northern Hospital
• Investigators: Principal Investigator: Yaling Han, MD, Shenyang Northern Hospital,China

Publications and helpful links

General Publications

• Liang Z, Li Y, Wang J, Wang D, Wang S, Ma L, Liu H, Yang L, Stone GW, Han Y. The safety and effectiveness of bivalirudin in female patients with acute myocardial infarction undergoing primary angioplasty: A subgroup analysis of the BRIGHT trial. Catheter Cardiovasc Interv. 2016 Mar;87 Suppl 1:608-15. doi: 10.1002/ccd.26407. Epub 2016 Jan 13.
• Han Y, Guo J, Zheng Y, Zang H, Su X, Wang Y, Chen S, Jiang T, Yang P, Chen J, Jiang D, Jing Q, Liang Z, Liu H, Zhao X, Li J, Li Y, Xu B, Stone GW; BRIGHT Investigators. Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: the BRIGHT randomized clinical trial. JAMA. 2015 Apr 7;313(13):1336-46. doi: 10.1001/jama.2015.2323.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: August 22, 2012
• First Submitted That Met QC Criteria: September 25, 2012
• First Posted (Estimate): September 28, 2012

Study Record Updates

• Last Update Posted (Estimate): October 1, 2014
• Last Update Submitted That Met QC Criteria: September 30, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Acute myocardial infarction; percutaneous transluminal coronary angioplasty; Bivalirudin
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Heparin; Bivalirudin; Tirofiban; Calcium heparin
• Other Study ID Numbers: SYNH20120001; 2011BAI11B07 (Other Grant/Funding Number: China National Science and Technology support project plan)