STrategic Reperfusion in Elderly Patients Early After Myocardial Infarction (STREAM-2)

In patients ≥ 60yrs with acute ST-elevation myocardial infarction randomised within 3 hours of onset of symptoms the efficacy and safety of a strategy of early fibrinolytic treatment with half-dose tenecteplase and additional antiplatelet therapy with a loading dose of 300 mg clopidogrel, aspirin and coupled with antithrombin therapy followed by catheterisation within 6-24 hours or rescue coronary intervention as required, will be compared to a strategy of primary PCI with a P2Y12 antagonist and antithrombin treatment according to local standards.

Study Overview

• Status: Active, not recruiting
• Conditions: Myocardial Infarction
• Intervention / Treatment: Drug: Tenecteplase; Drug: Clopidogrel; Procedure: Coronary angiography; Procedure: Primary PCI

• Study Type: Interventional
• Enrollment (Actual): 609
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Liverpool, Australia, 2170
    • Liverpool Hospital - Cardiology Department
• Brazil
  • Campinas, Brazil
    • Centro de Pesquisa São Lucas - Hospital E Maternidade Celso Pierro
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
• Chile
  • Antofagasta, Chile, 1240801
    • Hospital Regional de Antofagasta
  • Mejillones, Chile, 1310000
    • Hospital Comunitario de Mejillones
  • Melipilla, Chile
    • Hospital de Melipilla
  • Rancagua, Chile, 2820000
    • Hospital Regional de Rancagua
  • Rancagua, Chile, 2830945
    • SAR Rancagua
  • Santiago, Chile, 8350488
    • Hospital San Juan de Dios
  • Talagante, Chile, 9670468
    • Hospital de Talagante
  • Tocopilla, Chile, 1340000
    • Hospital de Tocopilla
• France
  • Bron, France, 69677
    • CH Louis Pradel - Hospices civils de Lyon
  • Cahors, France, 46005
    • CH Cahors - SAMU 46
  • Châteauroux, France, 36019
    • CH de Châteauroux
  • Corbeil-Essonnes, France, 91106
    • CH Sud Francilien - Service Cardiologie
  • Le Chesnay, France, 78157
    • Centre Hospitalier de Versailles
  • Lille, France, 59037
    • CHRU de Lille
  • Lyon, France, 69365
    • CH St. Joseph - St Luc - Lyon
  • Melun, France
    • Groupe Hospitalier Sud Ile de France - CH de Melun - Service SAMU 77
  • Montauban, France, 82000
    • Clinque du Pont de Chaume
  • Rennes, France
    • Chu de Rennes
  • Vienne, France, 38209
    • CH Lucien Hussel
• Mexico
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Cardiologia Ignacio Chavez
  • Mexico City, Mexico, 14080
    • Hospital Gea Gonzalez
• Montenegro
  • Bar, Montenegro
    • JZU Blazo Orlandic
  • Cetinje, Montenegro
    • General Hospital Danilo the First Cetinje
  • Nikšić, Montenegro
    • General Hospital of Niksic
  • Podgorica, Montenegro
    • Clinical Centar of Montenegro
• Russian Federation
  • Kemerovo, Russian Federation
    • Federal State Budgetary Inst "Research Inst. for Complex Issues of Card. Diseases"
  • Kemerovo, Russian Federation
    • State Budgetary Healthcare Inst. Kemerovo-Clinical Emergency Care Station
  • Tomsk, Russian Federation, 634012
    • Federal State Budgetary Scientific Inst "Tomsk Nat Research Med.Center of Russian Academy Sciences"
  • Tomsk, Russian Federation, 634059
    • Tomsk Regional State Autonomous Healthcare Institution Emergency Care Station
  • Tver, Russian Federation
    • State Budgetary Healthcare Institution of Tverskoy Region "Region Clinical Hospital"
  • Tver, Russian Federation
    • Tver Region State Budgetary Healthcare Institution "Tver Emergency Station"
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia, Cardiology Clinic
  • Belgrade, Serbia, 11000
    • Military Medical Academy, Clinic for Emergency Internal Medicine
  • Belgrade, Serbia, 11040
    • Institute for cardiovascular diseases Dedinje, Cardiovascular research sector
  • Cuprija, Serbia, 35230
    • General Hospital Cuprija, Cardiology Department
  • Jagodina, Serbia, 35000
    • General Hospital Jagodina/Intenal Medicine department
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac, Cardiology Clinic
  • Pančevo, Serbia, 26000
    • General Hospital Pancevo/Department of internal medicine - cardiology section
  • Smederevo, Serbia, 11300
    • General Hospital "Sveti Luka" Smederevo, Dept of Internal Med - Cardiology Section
  • Sremska Kamenica, Serbia, 21204
    • Institute for cardiovascular diseases Vojvodina - Sremska Kamenica, Cardiology Clinic
  • Vrbas, Serbia
    • Opsta bolnica Vrbas, Cardiology Department
  • Vršac, Serbia, 26300
    • General Hospital Vrsac/Cardiology department with coronary unit
  • Šabac, Serbia, 15000
    • General Hospital "Dr. Laza K. Lazarevic" Sabac, Internal medicine department
• Spain
  • Málaga, Spain, 29010
    • Hospital Virgen de la Victoria, Unidad de Cuidados Intensivos
  • Málaga, Spain, 29200
    • Hospital de Antequera, Unidad de Cuidados Intensivos
  • Málaga, Spain, 29400
    • Hospital Serrania Ronda, Unidad de Cuidados Intensivos
  • Málaga, Spain, 29740
    • Hospital Comarcal Axarquia, Unidad de Cuidados Intensivos

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age equal or greater than 60 years
2. Onset of symptoms < 3 hours prior to randomisation

3. 12-lead ECG indicative of an acute STEMI (ST-elevation will be measured from the J point; scale: 1 mm per 0.1 mV):

   • ≥ 2 mm ST-elevation across 2 contiguous precordial leads (V1-V6) or leads I and aVL for a minimum combined total of ≥ 4 mm ST-elevation or
   • ≥ 2 mm ST-elevation in 2 contiguous inferior leads (II, III, aVF) for a minimum combined total of ≥ 4 mm ST-elevation
4. Informed consent received

Exclusion Criteria:

1. 1. Expected performance of PCI < 60 minutes from diagnosis (qualifying ECG) or inability to arrive at the catheterisation laboratory within 3 hours
2. Previous CABG
3. Left bundle branch block or ventricular pacing
4. Patients with cardiogenic shock - Killip Class 4
5. Patients with a body weight < 55 kg (known or estimated)
6. Uncontrolled hypertension, defined as sustained blood pressure ≥ 180/110 mm Hg (systolic BP ≥ 180 mm Hg and/or diastolic BP ≥ 110 mm Hg) prior to randomisation
7. Known prior stroke or TIA
8. Recent administration of any i.v. or s.c. anticoagulation within 12 hours, including unfractionated heparin, enoxaparin, and/or bivalirudin or current use of oral anticoagulation (i.e. warfarin or a NOACs)
9. Active bleeding or known bleeding disorder/diathesis
10. Known history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery) or recent trauma to the head or cranium (i.e. < 3 months)
11. Major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months (this includes any trauma associated with the current myocardial infarction)
12. Clinical diagnosis associated with increased risk of bleeding including known active peptic ulceration and/or neoplasm with increased bleeding risk
13. Prolonged cardiopulmonary resuscitation (> 2 minutes) within the past 2 weeks
14. Known acute pericarditis and/or subacute bacterial endocarditis
15. Known acute pancreatitis or known severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis
16. Dementia
17. Known severe renal insufficiency
18. Previous enrolment in this study or treatment with an investigational drug or device under another study protocol in the past 7 days
19. Known allergic reactions to tenecteplase, clopidogrel, enoxaparin and aspirin
20. Inability to follow the protocol and comply with follow-up requirements or any other reason that the investigator feels would place the patient at increased risk if the investigational therapy is initiated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pharmaco-invasive strategy; Half-dose tenecteplase and additional antiplatelet therapy with a loading dose of 300 mg clopidogrel, aspirin and coupled with antithrombin therapy followed by coronary angiography within 6-24 hours or rescue coronary intervention as required.	Drug: Tenecteplase; Half dose Tenecteplase; Other Names: TNKase; Metalyse; Drug: Clopidogrel; 300 mg p.o. initial loading dose. Maintenance dose of 75 mg p.o. once daily. The maintenance dose of Clopidogrel (75 mg p.o. per day) should be continued for 1 year.; Procedure: Coronary angiography; Coronary angiography followed by PCI or CABG if required, rescue PCI if required
Active Comparator: Standard primary PCI; Primary PCI with a P2Y12 antagonist and antithrombin treatment according to local standards.	Procedure: Primary PCI; Primary PCI accoring to local standards

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients achieving ≥ 50 % ST-segment resolution before and after PCI; needing rescue PCI; demonstrating TIMI flow grades (0,1,2,3); with aborted MI.		30 days
Number of patients with stroke (total, intracranial haemorrhage, ischaemic, haemorrhagic conversion) and non-intracranial bleeds. Number of patients with serious cardiac events.	Serious cardiac events (e.g. death , congestive heart failure, reinfarction, resuscitated ventricular fibrillation, repeat target vessel recanalization, stent thrombosis, total AV block etc).	30 days
Composite endpoints (e.g. death, shock, heart failure and recurrent MI) will be assessed as described in the statistical analytical plan.		30 days

Collaborators and Investigators

• Sponsor: KU Leuven
• Collaborators: Boehringer Ingelheim; Life Sciences Research Partners; Fund for Clinical Cardiovascular Research at LRD
• Investigators: Study Chair: Frans Van de Werf, MD, PhD, KU Leuven; Study Chair: Paul Armstrong, MD, University of Alberta, Edmonton, Canada; Principal Investigator: Peter Sinnaeve, MD, PhD, UZ Leuven, Belgium; Principal Investigator: Robert Welsh, MD, University of Alberta, Edmonton, Canada; Principal Investigator: Patrick Goldstein, MD, Lille University Hospital, France

Publications and helpful links

General Publications

• Armstrong PW, Gershlick AH, Goldstein P, Wilcox R, Danays T, Lambert Y, Sulimov V, Rosell Ortiz F, Ostojic M, Welsh RC, Carvalho AC, Nanas J, Arntz HR, Halvorsen S, Huber K, Grajek S, Fresco C, Bluhmki E, Regelin A, Vandenberghe K, Bogaerts K, Van de Werf F; STREAM Investigative Team. Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction. N Engl J Med. 2013 Apr 11;368(15):1379-87. doi: 10.1056/NEJMoa1301092. Epub 2013 Mar 10.
• Sinnaeve PR, Armstrong PW, Gershlick AH, Goldstein P, Wilcox R, Lambert Y, Danays T, Soulat L, Halvorsen S, Ortiz FR, Vandenberghe K, Regelin A, Bluhmki E, Bogaerts K, Van de Werf F; STREAM investigators. ST-segment-elevation myocardial infarction patients randomized to a pharmaco-invasive strategy or primary percutaneous coronary intervention: Strategic Reperfusion Early After Myocardial Infarction (STREAM) 1-year mortality follow-up. Circulation. 2014 Sep 30;130(14):1139-45. doi: 10.1161/CIRCULATIONAHA.114.009570. Epub 2014 Aug 26.
• Dianati Maleki N, Van de Werf F, Goldstein P, Adgey JA, Lambert Y, Sulimov V, Rosell-Ortiz F, Gershlick AH, Zheng Y, Westerhout CM, Armstrong PW. Aborted myocardial infarction in ST-elevation myocardial infarction: insights from the STrategic Reperfusion Early After Myocardial infarction trial. Heart. 2014 Oct;100(19):1543-9. doi: 10.1136/heartjnl-2014-306023. Epub 2014 Jun 10.
• Sinnaeve PR, Danays T, Bogaerts K, Van de Werf F, Armstrong PW. Drug Treatment of STEMI in the Elderly: Focus on Fibrinolytic Therapy and Insights from the STREAM Trial. Drugs Aging. 2016 Feb;33(2):109-18. doi: 10.1007/s40266-016-0345-6.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): October 13, 2022
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: May 13, 2016
• First Submitted That Met QC Criteria: May 17, 2016
• First Posted (Estimate): May 19, 2016

Study Record Updates

• Last Update Posted (Estimate): December 22, 2022
• Last Update Submitted That Met QC Criteria: December 20, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Primary PCI; Thrombolytic Therapy
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Tenecteplase
• Other Study ID Numbers: LRD.2016.STREAM2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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