STrategic Reperfusion in Elderly Patients Early After Myocardial Infarction

NCT02777580 | Completed Phase 4 Results DMC

• 1 other identifier: LRD.2016.STREAM2
• Study Type: interventional
• Target: 609
• Locations: 10 countries
• Sites: 50

Brief Summary

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.

Conditions

Myocardial Infarction

Keywords

Thrombolytic Therapy; Primary PCI

Outcome Measures

Primary Outcomes (4)

• Successful Reperfusion

  Worst-lead ST-segment elevation resolution ≥ 50% 30 min post angiogram/PCI

  30 min post angiogram/PCI

• Composite Clinical Efficacy End Point: All Cause Death, Shock, CHF and Reinfarction at 30 Days

  30 days

• Total Stroke

  Number of patients with stroke (intracranial haemorrhage, ischaemic, haemorrhagic conversion)

  30 days

• Major Non-intrancranial Bleedings

  30 days

Study Arms (2)

Pharmaco-invasive strategy

EXPERIMENTAL

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; Drug: Clopidogrel; Procedure: Coronary angiography

Standard primary PCI

ACTIVE COMPARATOR

Primary PCI with a P2Y12 antagonist and antithrombin treatment according to local standards.

Procedure: Primary PCI

Interventions

Tenecteplase DRUG

Half dose Tenecteplase

Also known as: TNKase, Metalyse

Pharmaco-invasive strategy

Clopidogrel DRUG

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.

Pharmaco-invasive strategy

Coronary angiography PROCEDURE

Coronary angiography followed by PCI or CABG if required, rescue PCI if required

Pharmaco-invasive strategy

Primary PCI PROCEDURE

Primary PCI accoring to local standards

Standard primary PCI

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age equal or greater than 60 years
• Onset of symptoms \< 3 hours prior to randomisation
• 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
• Informed consent received

You may not qualify if:

• \. Expected performance of PCI \< 60 minutes from diagnosis (qualifying ECG) or inability to arrive at the catheterisation laboratory within 3 hours
• Previous CABG
• Left bundle branch block or ventricular pacing
• Patients with cardiogenic shock - Killip Class 4
• Patients with a body weight \< 55 kg (known or estimated)
• 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
• Known prior stroke or TIA
• 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)
• Active bleeding or known bleeding disorder/diathesis
• 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)
• 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)
• Clinical diagnosis associated with increased risk of bleeding including known active peptic ulceration and/or neoplasm with increased bleeding risk
• Prolonged cardiopulmonary resuscitation (\> 2 minutes) within the past 2 weeks
• Known acute pericarditis and/or subacute bacterial endocarditis
• Known acute pancreatitis or known severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis

Sponsors & Collaborators

• KU Leuven: lead
• Boehringer Ingelheim: collaborator
• Life Sciences Research Partners: collaborator
• Frans Van de Werf Fund for Clinical Cardiovascular Research: collaborator

Study Sites (50)

Liverpool Hospital - Cardiology Department

Liverpool, 2170, Australia

Location

Centro de Pesquisa São Lucas - Hospital E Maternidade Celso Pierro

Campinas, Brazil

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Hospital Regional de Antofagasta

Antofagasta, 1240801, Chile

Location

Hospital Comunitario de Mejillones

Mejillones, 1310000, Chile

Location

Hospital de Melipilla

Melipilla, Chile

Location

Hospital Regional de Rancagua

Rancagua, 2820000, Chile

Location

SAR Rancagua

Rancagua, 2830945, Chile

Location

Hospital San Juan de Dios

Santiago, 8350488, Chile

Location

Hospital de Talagante

Talagante, 9670468, Chile

Location

Hospital de Tocopilla

Tocopilla, 1340000, Chile

Location

CH Louis Pradel - Hospices civils de Lyon

Bron, 69677, France

Location

CH Cahors - SAMU 46

Cahors, 46005, France

Location

CH de Chateauroux

Châteauroux, 36019, France

Location

CH Sud Francilien - Service Cardiologie

Corbeil-Essonnes, 91106, France

Location

Centre Hospitalier de Versailles

Le Chesnay, 78157, France

Location

CHRU de Lille

Lille, 59037, France

Location

CH St. Joseph - St Luc - Lyon

Lyon, 69365, France

Location

Groupe Hospitalier Sud Ile de France - CH de Melun - Service SAMU 77

Melun, France

Location

Clinque du Pont de Chaume

Montauban, 82000, France

Location

CHU de Rennes

Rennes, France

Location

CH Lucien Hussel

Vienne, 38209, France

Location

Hospital Gea Gonzalez

Mexico City, 14080, Mexico

Location

Instituto Nacional de Cardiologia Ignacio Chavez

Mexico City, 14080, Mexico

Location

JZU Blazo Orlandic

Bar, Montenegro

Location

General Hospital Danilo the First Cetinje

Cetinje, Montenegro

Location

General Hospital of Niksic

Nikšić, Montenegro

Location

Clinical Centar of Montenegro

Podgorica, Montenegro

Location

Federal State Budgetary Inst "Research Inst. for Complex Issues of Card. Diseases"

Kemerovo, Russia

Location

State Budgetary Healthcare Inst. Kemerovo-Clinical Emergency Care Station

Kemerovo, Russia

Location

Federal State Budgetary Scientific Inst "Tomsk Nat Research Med.Center of Russian Academy Sciences"

Tomsk, 634012, Russia

Location

Tomsk Regional State Autonomous Healthcare Institution Emergency Care Station

Tomsk, 634059, Russia

Location

State Budgetary Healthcare Institution of Tverskoy Region "Region Clinical Hospital"

Tver', Russia

Location

Tver Region State Budgetary Healthcare Institution "Tver Emergency Station"

Tver', Russia

Location

Clinical Center of Serbia, Cardiology Clinic

Belgrade, 11000, Serbia

Location

Military Medical Academy, Clinic for Emergency Internal Medicine

Belgrade, 11000, Serbia

Location

Institute for cardiovascular diseases Dedinje, Cardiovascular research sector

Belgrade, 11040, Serbia

Location

General Hospital Cuprija, Cardiology Department

Ćuprija, 35230, Serbia

Location

General Hospital Jagodina/Intenal Medicine department

Jagodina, 35000, Serbia

Location

Institute for cardiovascular diseases Vojvodina - Sremska Kamenica, Cardiology Clinic

Kamenitz, 21204, Serbia

Location

Clinical Center Kragujevac, Cardiology Clinic

Kragujevac, 34000, Serbia

Location

General Hospital Pancevo/Department of internal medicine - cardiology section

Pančevo, 26000, Serbia

Location

General Hospital "Sveti Luka" Smederevo, Dept of Internal Med - Cardiology Section

Smederevo, 11300, Serbia

Location

General Hospital "Dr. Laza K. Lazarevic" Sabac, Internal medicine department

Šabac, 15000, Serbia

Location

Opsta bolnica Vrbas, Cardiology Department

Vrbas, Serbia

Location

General Hospital Vrsac/Cardiology department with coronary unit

Vršac, 26300, Serbia

Location

Hospital Virgen de la Victoria, Unidad de Cuidados Intensivos

Málaga, 29010, Spain

Location

Hospital de Antequera, Unidad de Cuidados Intensivos

Málaga, 29200, Spain

Location

Hospital Serrania Ronda, Unidad de Cuidados Intensivos

Málaga, 29400, Spain

Location

Hospital Comarcal Axarquia, Unidad de Cuidados Intensivos

Málaga, 29740, Spain

Location

Related Publications (8)

• 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.

  PMID: 23473396 BACKGROUND

• 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.

  PMID: 25161043 BACKGROUND

• 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.

  PMID: 24916050 BACKGROUND

• 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.

  PMID: 26849132 BACKGROUND

• Armstrong PW, Zheng Y, Welsh RC, Sinnaeve PR, de Werf FV, Westerhout CM, Bainey KR. Primary Percutaneous Coronary Intervention within the First Hour: Insights from Early-Treated Patients with ST-Elevation Myocardial Infarction. Am Heart J. 2026 Jan 29:107363. doi: 10.1016/j.ahj.2026.107363. Online ahead of print.

  PMID: 41619999 DERIVED

• Bainey KR, Welsh RC, Zheng Y, Arias-Mendoza A, Ristic AD, Averkov OV, Lambert Y, Temple T, Ly E, Bogaerts K, Sinnaeve P, Westerhout CM, Van de Werf F, Armstrong PW; STREAM-2 Investigators. Pharmaco-invasive strategy and dosing of tenecteplase in STEMI patients 60 to <75 years: An inter-trial comparison of the STREAM-1 and STREAM-2 trials. Am Heart J. 2025 Jun;284:20-31. doi: 10.1016/j.ahj.2025.02.002. Epub 2025 Feb 12.

  PMID: 39952376 DERIVED

• Bainey KR, Welsh RC, Zheng Y, Arias-Mendoza A, Ristic AD, Averkov OV, Lambert Y, Kerr Saraiva JF, Sepulveda P, Rosell-Ortiz F, French JK, Music LB, Temple T, Ly E, Bogaerts K, Sinnaeve PR, Danays T, Westerhout CM, Van de Werf F, Armstrong PW; STREAM-2 Investigators. Pharmaco-Invasive Strategy With Half-Dose Tenecteplase in Patients With STEMI: Prespecified Pooled Analysis of Patients Aged >/=75 Years in STREAM-1 and 2. Circ Cardiovasc Interv. 2024 Dec;17(12):e014251. doi: 10.1161/CIRCINTERVENTIONS.124.014251. Epub 2024 Dec 17.

  PMID: 39689189 DERIVED

• Van de Werf F, Ristic AD, Averkov OV, Arias-Mendoza A, Lambert Y, Kerr Saraiva JF, Sepulveda P, Rosell-Ortiz F, French JK, Music LB, Vandenberghe K, Bogaerts K, Westerhout CM, Pages A, Danays T, Bainey KR, Sinnaeve P, Goldstein P, Welsh RC, Armstrong PW; STREAM-2 Investigators. STREAM-2: Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment-Elevation Myocardial Infarction: A Randomized, Open-Label Trial. Circulation. 2023 Aug 29;148(9):753-764. doi: 10.1161/CIRCULATIONAHA.123.064521. Epub 2023 Jul 13.

  PMID: 37439219 DERIVED

MeSH Terms

Conditions

Myocardial Infarction

Interventions

Tenecteplase; Clopidogrel

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Prof Frans Van de Werf
• Organization: KU Leuven

frans.vandewerf@kuleuven.be

003216342111

Study Officials

• Frans Van de Werf, MD, PhD

  KU Leuven

  STUDY CHAIR

• Paul Armstrong, MD

  University of Alberta, Edmonton, Canada

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof Dr

Study Record Dates

• First Submitted: May 13, 2016
• First Posted: May 19, 2016
• Study Start: August 1, 2017
• Primary Completion: October 13, 2022
• Study Completion: September 30, 2023
• Last Updated: October 4, 2024
• Results First Posted: October 4, 2024

Record last verified: 2024-07

Locations

AU (1); ME (2); FR (11); CL (8); MO (4); ES (4); RU (6); BR (1); SE (12); CA (1)