Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis

Acute ST Segment Elevation Myocardial Infarction Clinical Trial

— TREAT  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02298088
• Other study ID #: TREAT01
• Status: Completed
• Phase: Phase 3
• Start date: August 2015
• Est. completion date: January 2019

Study information

• Verified date: February 2019
• Source: Hospital do Coracao
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3799
• Est. completion date: January 2019
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute ST Segment Elevation Myocardial Infarction
• Infarction
• Myocardial Infarction
• ST Elevation Myocardial Infarction
• Thrombolysis in Myocardial Infarction Flow

Intervention

Drug:
• Ticagrelor 180 mg
Ticagrelor, 180 mg as early as possible after the index event and not >24 h post event followed by 90 mg twice daily for 12 months.
• Clopidogrel
300 mg clopidogrel as early as possible after the index event and not > 24h post event, followed by 75mg/day for 12 months. For patients with > 75 years the recommended load dose is 75 mg instead 300 mg.

Locations

Country	Name	City	State
Argentina	Hospital Interzonal General de Agudos Dr, José Penna	Bahia Blanca
Argentina	Hospital Alvarez	Ciudad Autonoma de Buenos Aires
Argentina	Hospital Del Cruce Nestor Kishner	Florencio Varela
Argentina	Hospital Español de La Plata	La Plata
Argentina	Sanatorio Modelo de Quilmes	Quilmes
Argentina	Hospital Zenón Santillan	San Miguel de Tucuman
Australia	Flinders Medical Centre	Adelaide
Australia	Royal Adelaide Hospital	Adelaide
Australia	Cairns Hospital	Cairns
Australia	The Alfred Hospital	Melbourne
Australia	Mildura Hospital	Mildura
Australia	John Hunter Hospital	Newcastle
Australia	Fiona Stanley Hospital	Perth
Australia	Liverpool Hospital	Sydney
Australia	Townsville Hospital	Townsville
Australia	Wollongong Hospital	Wollongong
Brazil	Hospital das Clínicas - UFMG	Belo Horizonte
Brazil	Hospital Lifecenter	Belo Horizonte
Brazil	Hospital Universitario Sao Jose	Belo Horizonte
Brazil	Santa Case de Belo Horizonte	Belo Horizonte
Brazil	Hospital de Base do Distrito Federal	Brasília
Brazil	Instituto de Cardiologia do Distrito Federal	Brasília
Brazil	Hospital de Clinicas da Universidade Estadual de Campinas - UNICAMP	Campinas
Brazil	Hospital e Maternidade Celso Pierro	Campinas
Brazil	Hospital e Clinica Sao Roque	Ipiau
Brazil	Hospital e Pronto Socorro 28 de Agosto	Manaus
Brazil	Hospital de Messejana	Messejana
Brazil	Santa Casa de Montes Claros	Montes Claros
Brazil	Hospital Sao Vicente de Paulo	Passo Fundo
Brazil	Hospital Pronto Socorro e Maternidade Santa Lucia	Pocos de Caldas
Brazil	Instituto de Cardiologia - Fundação de Cardiologia (ICFUC)	Porto Alegre
Brazil	Hospital Agamenon Magalhaes	Recife
Brazil	Hospital Municipal de Emergencia Albert Sabin	Sao Caetano do Sul
Brazil	Santa Casa de Sao Jose do Rio Preto	Sao Jose do Rio Preto
Brazil	Hospital do Coracao	Sao Paulo
Brazil	Hospital do Mandaqui	Sao Paulo
Brazil	Hospital Geral do Grajau / UNISA	Sao Paulo
Brazil	Hospital Municipal do Campo Limpo	Sao Paulo
Brazil	Hospital TotalCor	Sao Paulo
Brazil	PreventSenior	Sao Paulo
Brazil	Universidade Federal de Sao Paulo	Sao Paulo
Brazil	Cardiolima	Teresina
Canada	Royal Alexandra Hospital	Edmonton
Canada	University of Alberta Hospital	Edmonton
Canada	Queen Elizabeth II Health Sciences Centre	Halifax
Canada	University Hospital / London Health Sciences Centre - Interventional Cardiology	London
Canada	Southlake Regional Health Centre - Interventional Cardiology	Newmarket
Canada	University of Ottawa Heart Institute	Ottawa
Canada	Peterborough Regional Health Centre	Peterborough
Canada	Inst Uni de Cardiologie et Pneumologie de Quebec	Quebec
Canada	Regina General Hospital - Prairie Vascular Research Network (PVRN) - SETFAST Coordinating Centre (SCC)	Regina
Canada	New Brunswick Heart Centre Research Initiative	Saint John
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke
Canada	Thunder Bay Regional Health Sciences Centre - Cardiac Cath Lab	Thunder Bay
Canada	Centre Intégré Universitaire de santé et de services sociaux de la Mauricie-et-du-Centre-du-Québec	Trois-Rivieres
Canada	Victoria Heart Institute Foundation	Victoria,
Canada	St. Mary's General Hospital	Waterloo
Canada	Windsor Regional Hospital	Windsor
Canada	St. Boniface General Hospital	Winnipeg
China	Alxa League Central Hospital	Alashan
China	Anshan Changda Hospital	Anshan
China	Third affiliated hospital of Inner Mongolia medical university	Baotou
China	Urad Front Banner People's Hospital	Bayan Nur
China	The First Hospital of Fangshan District, Beijing	Beijing
China	Benxi Jinshan Hospital	Benxi
China	Binzhou City Center Hospital	Binzhou
China	Changyuan County People's Hospital	Changyuan
China	Chaoyang Second People's Hospital	Chaoyang
China	Dengfeng People's Hospital	Dengfeng
China	Dunhua Hospital	Dunhua
China	Fushun Mining Bureau General Hospital	Fushun
China	Gongyi People's Hospital	Gongyi
China	Hulunbuir People's Hospital	Harbin
China	Qi County People's Hospital	Hebi
China	Heze Municipal Hospital	Heze
China	Hunchun People's Hospital	Hunchun
China	Wen Country People´s Hospital	Jiaozuo
China	Laixi People's Hospital	Laixi
China	The Second Hospital of Liaocheng	Liaocheng
China	The Third People's Hospital of LiaoYang	Liaoyang
China	Dongfeng County Hospital	Liaoyuan
China	Houma People's Hospital	Linfen
China	Lingbao First People's Hospital	Lingbao
China	Ruyang People's Hospital	Luoyang
China	Anhui Province Mengcheng County, People's Hospital	Mengcheng
China	Puyang Zhongyuan Oil field General Hospital	Puyang
China	Qinyang People's Hospital	Qinyang
China	Sanmenxia Central Hospital	Sanmenxia
China	Shangqiu Changzheng People's Hospital	Shangqiu
China	Shenyang Sujiatun District Central Hospital	Shenyang
China	Shenyang the Fourth Hospital of People	Shenyang
China	Xinmin People's Hospital	Shenyang
China	Jingxing County Hospital	Shijiazhuang
China	Laoting Hospital	Tangshan
China	Wuchuan People's Hospital	Wuchuan
China	Wuhai People's Hospital	Wuhai
China	Affiliated PuAi Hospital of Tongji Medical College	Wuhan
China	Wuyishan Municipal Hospital	Wuyishan
China	Qinghai Cardiovascular Hospital	Xining
China	Feng County People's Hospita	Xuzhou
China	Yongcheng People's Hospital	Yongcheng
China	Jiang Hua Yao Autonomous County People's Hospital	Yongzhou
China	The First People's Hospital of YueYang	Yueyang
China	Zhangye People's Hospital	Zhangye
China	Dancheng County People's Hospital	Zhoukou
China	Huaiyang County People's Hospital	Zhoukou
Colombia	Foundation Cardiomet Cequin	Armenia
Colombia	Centro de Diagnostico Cardiologico Ltda	Cartagena
New Zealand	Hawkes Bay Hospital	Hastings
New Zealand	Nelson Hospital	Nelson
New Zealand	Taranaki Hospital	New Plymouth
New Zealand	Rotorua Hospital	Rotorua
New Zealand	Tauranga Hospital	Tauranga
New Zealand	Thames Hospital	Thames
New Zealand	Whangarei Base Hopsital	Whangarei
Peru	Hospital Regional Lamabayeque	Chiclayo
Peru	Clínica Internacional	Lima
Peru	Clínica San Pablo	Lima
Peru	Hospital Cayetano Heredia	Lima
Peru	Hospital Hipólito Unanue	Lima
Russian Federation	Regional State Budget Healthcare Institution Altai Regional Cardiology Dispensary	Barnaul
Russian Federation	State Healthcare Institution "Belgorod regional clinical hospital named after Prelate Ioasaf	Belgorod
Russian Federation	State Budget Healthcare Institution "Chelyabinsk regional clinical hospital #3"	Chelyabinsk
Russian Federation	State Budget Healthcare Institution Leningrad region Gatchina Clinical Inter-district Hospital	Gatchina
Russian Federation	State Healthcare Institution Irkutsk regional clinical hospital	Irkutsk
Russian Federation	Kirov Regional State Budget Healthcare Institution Kirov City clinical hospital #1	Kirov
Russian Federation	Regional State Budget Healthcare Institution Krasnoyarsk Regional Clinical Hospital	Krasnoyarsk
Russian Federation	Municipal Healthcare Institution Lyubertsy regional Hospital #2	Lyubertsy
Russian Federation	State Regional Budget Healthcare Institution Murmansk region Clinical Hospital named after P.A. Bayandin	Murmansk
Russian Federation	State Budget Healthcare Institution Novosibirsk region City Clinical Hospital #34	Novosibirsk
Russian Federation	Institution of the Russian academy of sciences Hospital of Pushchino Research Center of RAS	Pushchino
Russian Federation	Municipal Budget Healthcare Institution Rostov-on-Don City Emergency Care Hospital	Rostov-on-Don
Russian Federation	State Budget Healthcare Institution Ryazan region Regional Clinical Hospital	Ryazan
Russian Federation	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"	Smolensk
Russian Federation	Federal State Budget Science Institution "Science and Research Institute of Cardiology"	Tomsk
Russian Federation	State Healthcare Institution of Tula Region "Tula regional clinical hospital	Tula
Russian Federation	Tver Regional Clinical Hospital	Tver
Russian Federation	State Budget Healthcare Institution Vladimir region City Hospital #4	Vladimir
Russian Federation	Budget Healthcare Institution Voronezh region City Clinical Emergency Care Hospital #1	Voronezh
Russian Federation	State Budget Healthcare Institution of Yaroslavl region "Regional clinical hospital"	Yaroslavl
Ukraine	Cherkasy Regional Cardiology Center, Department of Acute Heart Failure and Arrythmia	Cherkasy
Ukraine	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	Ivano-Frankivsk
Ukraine	Municipal Healthcare Institution "Kharkiv City Clinical Hospital #8", Cardiology Department for MI patients N1, Kharkiv Medical Academy of Postgraduate Education	Kharkiv
Ukraine	SI "National Institut of Therapy named after L.T. Malaya NAMS of Ukraine", Department of Acute Myocardial Infarction	Kharkiv
Ukraine	Kiev Oleksandrivsk Clinical Hospital, department of Cardiology Reanimation, National Medical University named after O.O. Bogomolets, Chair of Internal Medicine ?2	Kyiv
Ukraine	Kyiv City Clinical Hospital #1, Department of Emergency Cardiology	Kyiv
Ukraine	Kyiv Emergency Care Hospital, Infarction Department	Kyiv
Ukraine	City Clinical Hospital # 1	Mykolaiv
Ukraine	MI "City Clinical Hospital N3 named after prof. K.J. Alejnikovoi", department of intensice cardiology care unit	Odesa
Ukraine	MI "Rivne Regional Clinical Hospital"	Rivne
Ukraine	Sumy regional Cardiology Dispensary	Sumy
Ukraine	MI "Regional Medical Center of Cardiovascular Diseases" of Zaporizhzhia Regional Council, Intensive Care Unit	Zaporizhzhya
Ukraine	Municipal Institution " Central city clinical hospital N1", cardiology department for MI patients	Zhytomyr

Sponsors (1)

Lead Sponsor	Collaborator
Hospital do Coracao

Countries where clinical trial is conducted

Argentina,  Australia,  Brazil,  Canada,  China,  Colombia,  New Zealand,  Peru,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Outcome as a measure of Time to TIMI-defined first major bleeding	The primary safety endpoint is time to TIMI-defined and adjudicated first major bleeding event (including major life-threatening bleeding and other major bleeding).; Bleeding TIMI Definition; Major: Any intracranial hemorrhage (ICH)*, OR Clinically significant overt signs of hemorrhage associated with a drop in hemoglobin (Hgb) of = 5 g/dL (or, when Hgb is not available, an absolute drop in hematocrit (Hct) of = 15%).; An independent blinded central adjudication committee will adjudicate all suspected primary end points.	30 days
Secondary	Efficacy Outcome as a measure of major cardiovascular events	Secondary efficacy combined endpoint: death from vascular causes, myocardial infarction, stroke, severe recurrent ischemia, recurrent ischemia, TIA, or other arterial thrombotic event.; We will also measure the individual outcomes all-cause mortality and need for rescue PCI, as well as individual components of the combined efficacy endpoint.	12 months
Secondary	Safety Outcome as a measure of bleeding event	Secondary safety endpoints: Total bleeding (major and minor) according to PLATO, TIMI and BARC definitions, minor bleeding according to the TIMI definition and major bleeding as individual endpoint according to the PLATO definition. Others safety variables will include: dyspnea, arrhythmia, bradycardia and laboratory safety tests	12 months