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

Phase 3

Completed

• Conditions: Thrombolysis in Myocardial Infarction Flow; Acute ST Segment Elevation Myocardial Infarction
• Interventions: Drug: Ticagrelor 180 mg; Drug: Clopidogrel

• Registration Number: NCT02298088
• Lead Sponsor: Hospital do Coracao

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.

Study Timeline

• Study First Submitted: 2014-10-27
• Study First Submitted QC: 2014-11-19
• Study First Posted: 2014-11-21
• Study Start: 2015-08
• Primary Completion: 2017-12
• Study Completion: 2019-01
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-12
• Last Update Posted: 2019-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3799

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ticagrelor 180 mg	Ticagrelor 180 mg	Patients assigned to Ticagrelor will receive oral 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	Clopidogrel	Patients will take the 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.

Primary Outcome Measures

Name	Time	Method
Safety Outcome as a measure of Time to TIMI-defined first major bleeding	30 days	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.

Secondary Outcome Measures

Name	Time	Method
Efficacy Outcome as a measure of major cardiovascular events	12 months	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.
Safety Outcome as a measure of bleeding event	12 months	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

Trial Locations

Locations (153)

Hospital Alvarez; 🇦🇷 Ciudad Autonoma de Buenos Aires, Argentina

Hospital Cayetano Heredia; 🇵🇪 Lima, Peru

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

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

Regional State Budget Healthcare Institution Krasnoyarsk Regional Clinical Hospital; 🇷🇺 Krasnoyarsk, 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

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 Lyubertsy regional Hospital #2; 🇷🇺 Lyubertsy, Russian Federation

State Regional Budget Healthcare Institution Murmansk region Clinical Hospital named after P.A. Bayandin; 🇷🇺 Murmansk, 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

State Healthcare Institution of Tula Region "Tula regional clinical hospital; 🇷🇺 Tula, Russian Federation

Federal State Budget Science Institution "Science and Research Institute of Cardiology"; 🇷🇺 Tomsk, Russian Federation

Sumy regional Cardiology Dispensary; 🇺🇦 Sumy, Ukraine

Tver Regional Clinical Hospital; 🇷🇺 Tver, Russian Federation

State Budget Healthcare Institution Vladimir region City Hospital #4; 🇷🇺 Vladimir, Russian Federation

State Budget Healthcare Institution of Yaroslavl region "Regional clinical hospital"; 🇷🇺 Yaroslavl, Russian Federation

Kyiv City Clinical Hospital #1, Department of Emergency Cardiology; 🇺🇦 Kyiv, Ukraine

Kyiv Emergency Care Hospital, Infarction Department; 🇺🇦 Kyiv, Ukraine

MI "Rivne Regional Clinical Hospital"; 🇺🇦 Rivne, Ukraine

Municipal Institution " Central city clinical hospital N1", cardiology department for MI patients; 🇺🇦 Zhytomyr, Ukraine

Shenyang Sujiatun District Central Hospital; 🇨🇳 Shenyang, China

The Alfred Hospital; 🇦🇺 Melbourne, Australia

Mildura Hospital; 🇦🇺 Mildura, Australia

Qi County People's Hospital; 🇨🇳 Hebi, China

Laixi People's Hospital; 🇨🇳 Laixi, China

Wollongong Hospital; 🇦🇺 Wollongong, Australia

Wuhai People's Hospital; 🇨🇳 Wuhai, China

Foundation Cardiomet Cequin; 🇨🇴 Armenia, Colombia

Hospital Español de La Plata; 🇦🇷 La Plata, Argentina

Royal Adelaide Hospital; 🇦🇺 Adelaide, Australia

Fiona Stanley Hospital; 🇦🇺 Perth, Australia

Sanatorio Modelo de Quilmes; 🇦🇷 Quilmes, Argentina

Hospital de Clinicas da Universidade Estadual de Campinas - UNICAMP; 🇧🇷 Campinas, Brazil

Flinders Medical Centre; 🇦🇺 Adelaide, Australia

Hospital Interzonal General de Agudos Dr, José Penna; 🇦🇷 Bahia Blanca, Argentina

Hospital Del Cruce Nestor Kishner; 🇦🇷 Florencio Varela, Argentina

Hospital Zenón Santillan; 🇦🇷 San Miguel de Tucuman, Argentina

John Hunter Hospital; 🇦🇺 Newcastle, Australia

Wen Country People´s Hospital; 🇨🇳 Jiaozuo, China

Houma People's Hospital; 🇨🇳 Linfen, China

Puyang Zhongyuan Oil field General Hospital; 🇨🇳 Puyang, China

Shenyang the Fourth Hospital of People; 🇨🇳 Shenyang, China

Xinmin People's Hospital; 🇨🇳 Shenyang, China

Hospital de Messejana; 🇧🇷 Messejana, Brazil

Hospital Sao Vicente de Paulo; 🇧🇷 Passo Fundo, Brazil

Instituto de Cardiologia - Fundação de Cardiologia (ICFUC); 🇧🇷 Porto Alegre, Brazil

Dunhua Hospital; 🇨🇳 Dunhua, China

Dongfeng County Hospital; 🇨🇳 Liaoyuan, China

Lingbao First People's Hospital; 🇨🇳 Lingbao, China

Shangqiu Changzheng People's Hospital; 🇨🇳 Shangqiu, China

Santa Case de Belo Horizonte; 🇧🇷 Belo Horizonte, Brazil

Hospital das Clínicas - UFMG; 🇧🇷 Belo Horizonte, Brazil

Hospital Lifecenter; 🇧🇷 Belo Horizonte, Brazil

Hawkes Bay Hospital; 🇳🇿 Hastings, New Zealand

Clínica Internacional; 🇵🇪 Lima, Peru

Hunchun People's Hospital; 🇨🇳 Hunchun, China

Southlake Regional Health Centre - Interventional Cardiology; 🇨🇦 Newmarket, Canada

The Second Hospital of Liaocheng; 🇨🇳 Liaocheng, China

Anhui Province Mengcheng County, People's Hospital; 🇨🇳 Mengcheng, China

Laoting Hospital; 🇨🇳 Tangshan, China

Affiliated PuAi Hospital of Tongji Medical College; 🇨🇳 Wuhan, China

Jiang Hua Yao Autonomous County People's Hospital; 🇨🇳 Yongzhou, China

Zhangye People's Hospital; 🇨🇳 Zhangye, China

Ruyang People's Hospital; 🇨🇳 Luoyang, China

Qinyang People's Hospital; 🇨🇳 Qinyang, China

Jingxing County Hospital; 🇨🇳 Shijiazhuang, China

Thames Hospital; 🇳🇿 Thames, New Zealand

Hospital Regional Lamabayeque; 🇵🇪 Chiclayo, Peru

Wuchuan People's Hospital; 🇨🇳 Wuchuan, China

Huaiyang County People's Hospital; 🇨🇳 Zhoukou, China

Taranaki Hospital; 🇳🇿 New Plymouth, New Zealand

Tauranga Hospital; 🇳🇿 Tauranga, New Zealand

Centro de Diagnostico Cardiologico Ltda; 🇨🇴 Cartagena, Colombia

Clínica San Pablo; 🇵🇪 Lima, Peru

Qinghai Cardiovascular Hospital; 🇨🇳 Xining, China

Feng County People's Hospita; 🇨🇳 Xuzhou, China

Yongcheng People's Hospital; 🇨🇳 Yongcheng, China

The First People's Hospital of YueYang; 🇨🇳 Yueyang, China

Dancheng County People's Hospital; 🇨🇳 Zhoukou, China

Nelson Hospital; 🇳🇿 Nelson, New Zealand

Rotorua Hospital; 🇳🇿 Rotorua, New Zealand

Cherkasy Regional Cardiology Center, Department of Acute Heart Failure and Arrythmia; 🇺🇦 Cherkasy, Ukraine

MI "City Clinical Hospital N3 named after prof. K.J. Alejnikovoi", department of intensice cardiology care unit; 🇺🇦 Odesa, Ukraine

MI "Regional Medical Center of Cardiovascular Diseases" of Zaporizhzhia Regional Council, Intensive Care Unit; 🇺🇦 Zaporizhzhya, Ukraine

Whangarei Base Hopsital; 🇳🇿 Whangarei, New Zealand

Cairns Hospital; 🇦🇺 Cairns, Australia

Liverpool Hospital; 🇦🇺 Sydney, Australia

Townsville Hospital; 🇦🇺 Townsville, Australia

Hospital Universitario Sao Jose; 🇧🇷 Belo Horizonte, Brazil

Hospital de Base do Distrito Federal; 🇧🇷 Brasília, Brazil

Instituto de Cardiologia do Distrito Federal; 🇧🇷 Brasília, 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 Pronto Socorro e Maternidade Santa Lucia; 🇧🇷 Pocos de Caldas, Brazil

Santa Casa de Montes Claros; 🇧🇷 Montes Claros, 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 Geral do Grajau / UNISA; 🇧🇷 Sao Paulo, Brazil

Hospital do Mandaqui; 🇧🇷 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, Brazil

Royal Alexandra Hospital; 🇨🇦 Edmonton, Canada

University of Alberta Hospital; 🇨🇦 Edmonton, Canada

University Hospital / London Health Sciences Centre - Interventional Cardiology; 🇨🇦 London, Canada

Peterborough Regional Health Centre; 🇨🇦 Peterborough, Canada

Inst Uni de Cardiologie et Pneumologie de Quebec; 🇨🇦 Quebec, Canada

University of Ottawa Heart Institute; 🇨🇦 Ottawa, 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

St. Mary's General Hospital; 🇨🇦 Waterloo, Canada

Windsor Regional Hospital; 🇨🇦 Windsor, Canada

Urad Front Banner People's Hospital; 🇨🇳 Bayan Nur, China

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

Dengfeng People's Hospital; 🇨🇳 Dengfeng, China

St. Boniface General Hospital; 🇨🇦 Winnipeg, Canada

Alxa League Central Hospital; 🇨🇳 Alashan, China

Anshan Changda Hospital; 🇨🇳 Anshan, China

Third affiliated hospital of Inner Mongolia medical university; 🇨🇳 Baotou, China

The First Hospital of Fangshan District, Beijing; 🇨🇳 Beijing, China

Benxi Jinshan Hospital; 🇨🇳 Benxi, China

Chaoyang Second People's Hospital; 🇨🇳 Chaoyang, China

Binzhou City Center Hospital; 🇨🇳 Binzhou, China

Changyuan County People's Hospital; 🇨🇳 Changyuan, China

Fushun Mining Bureau General Hospital; 🇨🇳 Fushun, China

Gongyi People's Hospital; 🇨🇳 Gongyi, China

Heze Municipal Hospital; 🇨🇳 Heze, China

Hulunbuir People's Hospital; 🇨🇳 Harbin, China

The Third People's Hospital of LiaoYang; 🇨🇳 Liaoyang, China

Sanmenxia Central Hospital; 🇨🇳 Sanmenxia, China

Wuyishan Municipal Hospital; 🇨🇳 Wuyishan, China

Regional State Budget Healthcare Institution Altai Regional Cardiology Dispensary; 🇷🇺 Barnaul, Russian Federation

Hospital Hipólito Unanue; 🇵🇪 Lima, Peru

Budget Healthcare Institution Voronezh region City Clinical Emergency Care Hospital #1; 🇷🇺 Voronezh, Russian Federation

Kiev Oleksandrivsk Clinical Hospital, department of Cardiology Reanimation, National Medical University named after O.O. Bogomolets, Chair of Internal Medicine №2; 🇺🇦 Kyiv, Ukraine

City Clinical Hospital # 1; 🇺🇦 Mykolaiv, Ukraine

Queen Elizabeth II Health Sciences Centre; 🇨🇦 Halifax, Canada