Clinical trial NCT02298088: Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis
Official title: Phase III, Randomized, International, Multicenter, Open Label, With Blinded Adjudication of Outcomes, Non-Inferiority Clinical Trial to Explore the Safety and Efficacy of Ticagrelor Compared With Clopidogrel in Patients With Acute Coronary Syndrome With ST Elevation Treated With Pharmacological Thrombolysis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute ST Segment Elevation Myocardial Infarction
Thrombolysis in Myocardial Infarction Flow
Lead sponsor: Hospital do Coracao
Sponsor class: OTHER
First posted: 2014-11-21
Enrollment: 3799
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Administration of Ticagrelor in patients with ST elevation myocardial infarction treated with pharmacological thrombolysis

Detailed description: Phase III, Randomized, International, Multicenter, Open label, with Blinded Adjudication of Outcomes, Non-Inferiority Clinical Trial to Explore the Safety and Efficacy of Ticagrelor Compared with Clopidogrel in Patients with Acute Coronary Syndrome with ST Elevation Treated with Pharmacological Thrombolysis.

Eligibility criteria: Inclusion Criteria:

* Patients of both sexes aged ≥ 18 years and \< 75 years with ACS with ST segment elevation with onset during the previous 24 hours, documented by cardiac ischemic symptoms due to atherosclerosis of \> 10 minutes duration at rest, treated with pharmacological thrombolysis
* Fibrinolytic therapy should be given to patients with STEMI and onset of ischemic symptoms within the previous 12 hours

Patients with acute coronary syndrome with ST segment elevation will be included provided they present ST segment elevation at the J point in two contiguous leads in electrocardiogram with cut-points: \> 0.1mV in all leads other than leads V2-V3, where the following cut points apply: \> 0.2 mV in men \> 40 years; \> 0.25 mV in men \< 40 years, or \>0.15 mV in women and at least 1 of the following criteria:

* Angina-like chest pain or ischemic equivalent chest pain;
* Abnormalities above the reference value for markers of myocardial necrosis (troponin and CK-MB).

The patient must be able to give informed consent in accordance with ICH GCP guidelines and local legislation and/or regulations.

Exclusion Criteria:

* Any contraindication against the use of clopidogrel (eg, hypersensitivity, moderate or severe liver disease, active bleeding or bleeding history, history of intracranial hemorrhage)
* Need for oral anticoagulation therapy,
* Concomitant oral or IV therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, grapefruit juice N1 L/d), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or strong CYP3Ainducers (rifampin/rifampicin, phenytoin, carbamazepine)
* Increased risk of bradycardia events
* Dialysis required
* Known clinically important thrombocytopenia
* Known clinically important anemia
* Any other condition that may put the patient at risk or influence study results in the investigators' opinion (eg, cardiogenic shock, severe hemodynamic instability, active cancer)
* Participant in another investigational drug or device study within 30 d
* Pregnancy or lactation
* Any condition that increases the risk for noncompliance or being lost to follow-up
* Involvement in the planning or conduct of the study
* Previous enrollment or randomization in this study
* Contraindications to fibrinolytic therapy including: 15

  * Any prior intracranial hemorrhage
  * Known structural cerebral vascular lesion (eg, Arterial Venous Malformation - AVM)
  * Known malignant intracranial neoplasm (primary or metastatic)
  * Ischemic stroke within 3 months
  * Suspected aortic dissection
  * Active bleeding or bleeding diathesis (excluding menses)
  * Significant closed head trauma or facial trauma within 3 months

Primary outcomes:
measure: Safety Outcome as a measure of Time to TIMI-defined first major bleeding
timeFrame: 30 days
Secondary outcomes:
measure: Efficacy Outcome as a measure of major cardiovascular events
timeFrame: 12 months
measure: Safety Outcome as a measure of bleeding event
timeFrame: 12 months
Other outcomes:
Locations:
city: Bahia Blanca
country: Argentina
facility: Hospital Interzonal General de Agudos Dr, José Penna
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Alvarez
city: Florencio Varela
country: Argentina
facility: Hospital Del Cruce Nestor Kishner
city: La Plata
country: Argentina
facility: Hospital Español de La Plata
city: Quilmes
country: Argentina
facility: Sanatorio Modelo de Quilmes
city: San Miguel de Tucuman
country: Argentina
facility: Hospital Zenón Santillan
city: Adelaide
country: Australia
facility: Flinders Medical Centre
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Cairns
country: Australia
facility: Cairns Hospital
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Mildura
country: Australia
facility: Mildura Hospital
city: Newcastle
country: Australia
facility: John Hunter Hospital
city: Perth
country: Australia
facility: Fiona Stanley Hospital
city: Sydney
country: Australia
facility: Liverpool Hospital
city: Townsville
country: Australia
facility: Townsville Hospital
city: Wollongong
country: Australia
facility: Wollongong Hospital
city: Belo Horizonte
country: Brazil
facility: Hospital das Clínicas - UFMG
city: Belo Horizonte
country: Brazil
facility: Hospital Lifecenter
city: Belo Horizonte
country: Brazil
facility: Hospital Universitario Sao Jose
city: Belo Horizonte
country: Brazil
facility: Santa Case de Belo Horizonte
city: Brasília
country: Brazil
facility: Hospital de Base do Distrito Federal
city: Brasília
country: Brazil
facility: Instituto de Cardiologia do Distrito Federal
city: Campinas
country: Brazil
facility: Hospital de Clinicas da Universidade Estadual de Campinas - UNICAMP
city: Campinas
country: Brazil
facility: Hospital e Maternidade Celso Pierro
city: Ipiau
country: Brazil
facility: Hospital e Clinica Sao Roque
city: Manaus
country: Brazil
facility: Hospital e Pronto Socorro 28 de Agosto
city: Messejana
country: Brazil
facility: Hospital de Messejana
city: Montes Claros
country: Brazil
facility: Santa Casa de Montes Claros
city: Passo Fundo
country: Brazil
facility: Hospital Sao Vicente de Paulo
city: Pocos de Caldas
country: Brazil
facility: Hospital Pronto Socorro e Maternidade Santa Lucia
city: Porto Alegre
country: Brazil
facility: Instituto de Cardiologia - Fundação de Cardiologia (ICFUC)
city: Recife
country: Brazil
facility: Hospital Agamenon Magalhaes
city: Sao Caetano do Sul
country: Brazil
facility: Hospital Municipal de Emergencia Albert Sabin
city: Sao Jose do Rio Preto
country: Brazil
facility: Santa Casa de Sao Jose do Rio Preto
city: Sao Paulo
country: Brazil
facility: Hospital do Coracao
city: Sao Paulo
country: Brazil
facility: Hospital do Mandaqui
city: Sao Paulo
country: Brazil
facility: Hospital Geral do Grajau / UNISA
city: Sao Paulo
country: Brazil
facility: Hospital Municipal do Campo Limpo
city: Sao Paulo
country: Brazil
facility: Hospital TotalCor
city: Sao Paulo
country: Brazil
facility: PreventSenior
city: Sao Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo
city: Teresina
country: Brazil
facility: Cardiolima
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
city: Edmonton
country: Canada
facility: University of Alberta Hospital
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
city: London
country: Canada
facility: University Hospital / London Health Sciences Centre - Interventional Cardiology
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre - Interventional Cardiology
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
city: Peterborough
country: Canada
facility: Peterborough Regional Health Centre
city: Quebec
country: Canada
facility: Inst Uni de Cardiologie et Pneumologie de Quebec
city: Regina
country: Canada
facility: Regina General Hospital - Prairie Vascular Research Network (PVRN) - SETFAST Coordinating Centre (SCC)
city: Saint John
country: Canada
facility: New Brunswick Heart Centre Research Initiative
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Sciences Centre - Cardiac Cath Lab
city: Trois-Rivieres
country: Canada
facility: Centre Intégré Universitaire de santé et de services sociaux de la Mauricie-et-du-Centre-du-Québec
city: Victoria,
country: Canada
facility: Victoria Heart Institute Foundation
city: Waterloo
country: Canada
facility: St. Mary's General Hospital
city: Windsor
country: Canada
facility: Windsor Regional Hospital
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
city: Alashan
country: China
facility: Alxa League Central Hospital
city: Anshan
country: China
facility: Anshan Changda Hospital
city: Baotou
country: China
facility: Third affiliated hospital of Inner Mongolia medical university
city: Bayan Nur
country: China
facility: Urad Front Banner People's Hospital
city: Beijing
country: China
facility: The First Hospital of Fangshan District, Beijing
city: Benxi
country: China
facility: Benxi Jinshan Hospital
city: Binzhou
country: China
facility: Binzhou City Center Hospital
city: Changyuan
country: China
facility: Changyuan County People's Hospital
city: Chaoyang
country: China
facility: Chaoyang Second People's Hospital
city: Dengfeng
country: China
facility: Dengfeng People's Hospital
city: Dunhua
country: China
facility: Dunhua Hospital
city: Fushun
country: China
facility: Fushun Mining Bureau General Hospital
city: Gongyi
country: China
facility: Gongyi People's Hospital
city: Harbin
country: China
facility: Hulunbuir People's Hospital
city: Hebi
country: China
facility: Qi County People's Hospital
city: Heze
country: China
facility: Heze Municipal Hospital
city: Hunchun
country: China
facility: Hunchun People's Hospital
city: Jiaozuo
country: China
facility: Wen Country People´s Hospital
city: Laixi
country: China
facility: Laixi People's Hospital
city: Liaocheng
country: China
facility: The Second Hospital of Liaocheng
city: Liaoyang
country: China
facility: The Third People's Hospital of LiaoYang
city: Liaoyuan
country: China
facility: Dongfeng County Hospital
city: Linfen
country: China
facility: Houma People's Hospital
city: Lingbao
country: China
facility: Lingbao First People's Hospital
city: Luoyang
country: China
facility: Ruyang People's Hospital
city: Mengcheng
country: China
facility: Anhui Province Mengcheng County, People's Hospital
city: Puyang
country: China
facility: Puyang Zhongyuan Oil field General Hospital
city: Qinyang
country: China
facility: Qinyang People's Hospital
city: Sanmenxia
country: China
facility: Sanmenxia Central Hospital
city: Shangqiu
country: China
facility: Shangqiu Changzheng People's Hospital
city: Shenyang
country: China
facility: Shenyang Sujiatun District Central Hospital
city: Shenyang
country: China
facility: Shenyang the Fourth Hospital of People
city: Shenyang
country: China
facility: Xinmin People's Hospital
city: Shijiazhuang
country: China
facility: Jingxing County Hospital
city: Tangshan
country: China
facility: Laoting Hospital
city: Wuchuan
country: China
facility: Wuchuan People's Hospital
city: Wuhai
country: China
facility: Wuhai People's Hospital
city: Wuhan
country: China
facility: Affiliated PuAi Hospital of Tongji Medical College
city: Wuyishan
country: China
facility: Wuyishan Municipal Hospital
city: Xining
country: China
facility: Qinghai Cardiovascular Hospital
city: Xuzhou
country: China
facility: Feng County People's Hospita
city: Yongcheng
country: China
facility: Yongcheng People's Hospital
city: Yongzhou
country: China
facility: Jiang Hua Yao Autonomous County People's Hospital
city: Yueyang
country: China
facility: The First People's Hospital of YueYang
city: Zhangye
country: China
facility: Zhangye People's Hospital
city: Zhoukou
country: China
facility: Dancheng County People's Hospital
city: Zhoukou
country: China
facility: Huaiyang County People's Hospital
city: Armenia
country: Colombia
facility: Foundation Cardiomet Cequin
city: Cartagena
country: Colombia
facility: Centro de Diagnostico Cardiologico Ltda
city: Hastings
country: New Zealand
facility: Hawkes Bay Hospital
city: Nelson
country: New Zealand
facility: Nelson Hospital
city: New Plymouth
country: New Zealand
facility: Taranaki Hospital
city: Rotorua
country: New Zealand
facility: Rotorua Hospital
city: Tauranga
country: New Zealand
facility: Tauranga Hospital
city: Thames
country: New Zealand
facility: Thames Hospital
city: Whangarei
country: New Zealand
facility: Whangarei Base Hopsital
city: Chiclayo
country: Peru
facility: Hospital Regional Lamabayeque
city: Lima
country: Peru
facility: Clínica Internacional
city: Lima
country: Peru
facility: Clínica San Pablo
city: Lima
country: Peru
facility: Hospital Cayetano Heredia
city: Lima
country: Peru
facility: Hospital Hipólito Unanue
city: Barnaul
country: Russian Federation
facility: Regional State Budget Healthcare Institution Altai Regional Cardiology Dispensary
city: Belgorod
country: Russian Federation
facility: State Healthcare Institution "Belgorod regional clinical hospital named after Prelate Ioasaf
city: Chelyabinsk
country: Russian Federation
facility: State Budget Healthcare Institution "Chelyabinsk regional clinical hospital #3"
city: Gatchina
country: Russian Federation
facility: State Budget Healthcare Institution Leningrad region Gatchina Clinical Inter-district Hospital
city: Irkutsk
country: Russian Federation
facility: State Healthcare Institution Irkutsk regional clinical hospital
city: Kirov
country: Russian Federation
facility: Kirov Regional State Budget Healthcare Institution Kirov City clinical hospital #1
city: Krasnoyarsk
country: Russian Federation
facility: Regional State Budget Healthcare Institution Krasnoyarsk Regional Clinical Hospital
city: Lyubertsy
country: Russian Federation
facility: Municipal Healthcare Institution Lyubertsy regional Hospital #2
city: Murmansk
country: Russian Federation
facility: State Regional Budget Healthcare Institution Murmansk region Clinical Hospital named after P.A. Bayandin
city: Novosibirsk
country: Russian Federation
facility: State Budget Healthcare Institution Novosibirsk region City Clinical Hospital #34
city: Pushchino
country: Russian Federation
facility: Institution of the Russian academy of sciences Hospital of Pushchino Research Center of RAS
city: Rostov-on-Don
country: Russian Federation
facility: Municipal Budget Healthcare Institution Rostov-on-Don City Emergency Care Hospital
city: Ryazan
country: Russian Federation
facility: State Budget Healthcare Institution Ryazan region Regional Clinical Hospital
city: Smolensk
country: Russian Federation
facility: State Budget Educational Institution of Higher Professional Education "Smolensk State Medical University" Ministry of Healthcare of Russian Federation, clinical facility is State Budget Healthcare Institution "Smolensk regional clinical hospital"
city: Tomsk
country: Russian Federation
facility: Federal State Budget Science Institution "Science and Research Institute of Cardiology"
city: Tula
country: Russian Federation
facility: State Healthcare Institution of Tula Region "Tula regional clinical hospital
city: Tver
country: Russian Federation
facility: Tver Regional Clinical Hospital
city: Vladimir
country: Russian Federation
facility: State Budget Healthcare Institution Vladimir region City Hospital #4
city: Voronezh
country: Russian Federation
facility: Budget Healthcare Institution Voronezh region City Clinical Emergency Care Hospital #1
city: Yaroslavl
country: Russian Federation
facility: State Budget Healthcare Institution of Yaroslavl region "Regional clinical hospital"
city: Cherkasy
country: Ukraine
facility: Cherkasy Regional Cardiology Center, Department of Acute Heart Failure and Arrythmia
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Clinical Cardiological Dispensary, Department of Anestesiology and Intensive Care, SI"Ivano-Frankivsk National Medical University", Chair of Internal Medicine №2 and nurcering
city: Kharkiv
country: Ukraine
facility: Municipal Healthcare Institution "Kharkiv City Clinical Hospital #8", Cardiology Department for MI patients N1, Kharkiv Medical Academy of Postgraduate Education
city: Kharkiv
country: Ukraine
facility: SI "National Institut of Therapy named after L.T. Malaya NAMS of Ukraine", Department of Acute Myocardial Infarction
city: Kyiv
country: Ukraine
facility: Kiev Oleksandrivsk Clinical Hospital, department of Cardiology Reanimation, National Medical University named after O.O. Bogomolets, Chair of Internal Medicine №2
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital #1, Department of Emergency Cardiology
city: Kyiv
country: Ukraine
facility: Kyiv Emergency Care Hospital, Infarction Department
city: Mykolaiv
country: Ukraine
facility: City Clinical Hospital # 1
city: Odesa
country: Ukraine
facility: MI "City Clinical Hospital N3 named after prof. K.J. Alejnikovoi", department of intensice cardiology care unit
city: Rivne
country: Ukraine
facility: MI "Rivne Regional Clinical Hospital"
city: Sumy
country: Ukraine
facility: Sumy regional Cardiology Dispensary
city: Zaporizhzhya
country: Ukraine
facility: MI "Regional Medical Center of Cardiovascular Diseases" of Zaporizhzhia Regional Council, Intensive Care Unit
city: Zhytomyr
country: Ukraine
facility: Municipal Institution " Central city clinical hospital N1", cardiology department for MI patients
Study officials:
affiliation: Hospital do Coracao
name: Otavio Berwanger, MD,PhD
role: STUDY_CHAIR
affiliation: Hospital do Coracao
name: Helio P Guimaraes, MD,PhD
role: STUDY_CHAIR
affiliation: Hospital do Coracao
name: Leopoldo S Piegas, MD,PhD
role: STUDY_CHAIR
affiliation: Duke University
name: Renato D Lopes, MD,PhD
role: STUDY_CHAIR
affiliation: Instituto do Coracao HC-FMUSP
name: Jose C Nicolau, MD,PhD
role: STUDY_CHAIR
affiliation: Universidade Federal de São Paulo
name: Francisco A Fonseca, MD,PhD
role: STUDY_CHAIR
affiliation: Hospital e Maternidade Celso Pierro
name: Jose F Saraiva, MD,PhD
role: STUDY_CHAIR
affiliation: Investigación Independiente S.A.
name: Carlos Tajer, MD,PhD
role: STUDY_CHAIR
affiliation: South Australian Health and Medical Research Institute
name: Stephen Nicholls, MD,PhD
role: STUDY_CHAIR
affiliation: Canadian Heart Research Centre
name: Shaun Goodman, MD,PhD
role: STUDY_CHAIR
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Lixin Jiang, MD,PhD
role: STUDY_CHAIR
affiliation: Auckland City Hospital - Auckland District Health Board
name: Harvey White, MD,PhD
role: STUDY_CHAIR
affiliation: Universidad Peruana Cayetano Heredia
name: Germán Malaga, MD,PhD
role: STUDY_CHAIR
affiliation: Clinical Hospital #15 Clinical Hospital #15 named after O.M.Filatov, Moscow, Russia
name: Oleg Averkov, MD,PhD
role: STUDY_CHAIR
affiliation: Institute of Cardiology - Emergency Cardiology Department
name: Alexander Parkhomenko, MD,PhD
role: STUDY_CHAIR
affiliation: Duke University
name: Christopher Granger, MD,PhD
role: STUDY_CHAIR
References:
citation: Cantor WJ, Tan M, Berwanger O, Lavi S, White HD, Nicolau JC, Dehghani P, Tajer CD, Lopes RD, Moia DDF, Nicholls SJ, Parkhomenko A, Averkov O, Brass N, Lutchmedial S, Malaga G, Damiani LP, Piegas LS, Granger CB, Goodman SG. Morphine and clinical outcomes in patients with ST segment elevation myocardial infarction treated with fibrinolytic and antiplatelet therapy: Insights from the TREAT trial. Am Heart J. 2022 Sep;251:1-12. doi: 10.1016/j.ahj.2022.05.005. Epub 2022 May 6.
citation: Berwanger O, Lopes RD, Moia DDF, Fonseca FA, Jiang L, Goodman SG, Nicholls SJ, Parkhomenko A, Averkov O, Tajer C, Malaga G, Saraiva JFK, Guimaraes HP, de Barros E Silva PGM, Damiani LP, Santos RHN, Paisani DM, Miranda TA, Valeis N, Piegas LS, Granger CB, White HD, Nicolau JC. Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis: TREAT Trial. J Am Coll Cardiol. 2019 Jun 11;73(22):2819-2828. doi: 10.1016/j.jacc.2019.03.011. Epub 2019 Mar 18.
citation: Berwanger O, Nicolau JC, Carvalho AC, Jiang L, Goodman SG, Nicholls SJ, Parkhomenko A, Averkov O, Tajer C, Malaga G, Saraiva JFK, Fonseca FA, De Luca FA, Guimaraes HP, de Barros E Silva PGM, Damiani LP, Paisani DM, Lasagno CMR, Candido CT, Valeis N, Moia DDF, Piegas LS, Granger CB, White HD, Lopes RD; TREAT Study Group. Ticagrelor vs Clopidogrel After Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction: A Randomized Clinical Trial. JAMA Cardiol. 2018 May 1;3(5):391-399. doi: 10.1001/jamacardio.2018.0612.