STrategic Reperfusion in Elderly Patients Early After Myocardial Infarction

NCT ID: NCT02777580

Last Updated: 2024-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 609 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-01
• Study Completion Date: 2023-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Tenecteplase

Intervention Type: DRUG

Half dose Tenecteplase

Clopidogrel

Intervention Type: 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.

Coronary angiography

Intervention Type: PROCEDURE

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

Standard primary PCI

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

Group Type: ACTIVE_COMPARATOR

Primary PCI

Intervention Type: PROCEDURE

Primary PCI accoring to local standards

Interventions

Tenecteplase

Half dose Tenecteplase

Intervention Type: 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.

Intervention Type: DRUG

Coronary angiography

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

Intervention Type: PROCEDURE

Primary PCI

Primary PCI accoring to local standards

Intervention Type: PROCEDURE

Other Intervention Names

TNKase; Metalyse

Eligibility Criteria

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.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

Life Sciences Research Partners

OTHER

Sponsor Role: collaborator

Frans Van de Werf Fund for Clinical Cardiovascular Research

OTHER

Sponsor Role: collaborator

KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Frans Van de Werf

Prof Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Frans Van de Werf, MD, PhD

Role: STUDY_CHAIR

KU Leuven

Paul Armstrong, MD

Role: STUDY_CHAIR

University of Alberta, Edmonton, Canada

Peter Sinnaeve, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UZ Leuven, Belgium

Robert Welsh, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alberta, Edmonton, Canada

Patrick Goldstein, MD

Role: PRINCIPAL_INVESTIGATOR

Lille University Hospital, France

Locations

Liverpool Hospital - Cardiology Department

Liverpool, , Australia

Centro de Pesquisa São Lucas - Hospital E Maternidade Celso Pierro

Campinas, , Brazil

University of Alberta Hospital

Edmonton, Alberta, Canada

Hospital Regional de Antofagasta

Antofagasta, , Chile

Hospital Comunitario de Mejillones

Mejillones, , Chile

Hospital de Melipilla

Melipilla, , Chile

Hospital Regional de Rancagua

Rancagua, , Chile

SAR Rancagua

Rancagua, , Chile

Hospital San Juan de Dios

Santiago, , Chile

Hospital de Talagante

Talagante, , Chile

Hospital de Tocopilla

Tocopilla, , Chile

CH Louis Pradel - Hospices civils de Lyon

Bron, , France

CH Cahors - SAMU 46

Cahors, , France

CH de Chateauroux

Châteauroux, , France

CH Sud Francilien - Service Cardiologie

Corbeil-Essonnes, , France

Centre Hospitalier de Versailles

Le Chesnay, , France

CHRU de Lille

Lille, , France

CH St. Joseph - St Luc - Lyon

Lyon, , France

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

Melun, , France

Clinque du Pont de Chaume

Montauban, , France

CHU de Rennes

Rennes, , France

CH Lucien Hussel

Vienne, , France

Hospital Gea Gonzalez

Mexico City, , Mexico

Instituto Nacional de Cardiologia Ignacio Chavez

Mexico City, , Mexico

JZU Blazo Orlandic

Bar, , Montenegro

General Hospital Danilo the First Cetinje

Cetinje, , Montenegro

General Hospital of Niksic

Nikšić, , Montenegro

Clinical Centar of Montenegro

Podgorica, , Montenegro

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

Kemerovo, , Russia

State Budgetary Healthcare Inst. Kemerovo-Clinical Emergency Care Station

Kemerovo, , Russia

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

Tomsk, , Russia

Tomsk Regional State Autonomous Healthcare Institution Emergency Care Station

Tomsk, , Russia

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

Tver', , Russia

Tver Region State Budgetary Healthcare Institution "Tver Emergency Station"

Tver', , Russia

Clinical Center of Serbia, Cardiology Clinic

Belgrade, , Serbia

Military Medical Academy, Clinic for Emergency Internal Medicine

Belgrade, , Serbia

Institute for cardiovascular diseases Dedinje, Cardiovascular research sector

Belgrade, , Serbia

General Hospital Cuprija, Cardiology Department

Ćuprija, , Serbia

General Hospital Jagodina/Intenal Medicine department

Jagodina, , Serbia

Institute for cardiovascular diseases Vojvodina - Sremska Kamenica, Cardiology Clinic

Kamenitz, , Serbia

Clinical Center Kragujevac, Cardiology Clinic

Kragujevac, , Serbia

General Hospital Pancevo/Department of internal medicine - cardiology section

Pančevo, , Serbia

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

Smederevo, , Serbia

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

Šabac, , Serbia

Opsta bolnica Vrbas, Cardiology Department

Vrbas, , Serbia

General Hospital Vrsac/Cardiology department with coronary unit

Vršac, , Serbia

Hospital Virgen de la Victoria, Unidad de Cuidados Intensivos

Málaga, , Spain

Hospital de Antequera, Unidad de Cuidados Intensivos

Málaga, , Spain

Hospital Serrania Ronda, Unidad de Cuidados Intensivos

Málaga, , Spain

Hospital Comarcal Axarquia, Unidad de Cuidados Intensivos

Málaga, , Spain

Countries

Australia; Brazil; Canada; Chile; France; Mexico; Montenegro; Russia; Serbia; Spain

References

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.

Reference Type: BACKGROUND

PMID: 23473396 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25161043 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24916050 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26849132 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39952376 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39689189 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37439219 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

LRD.2016.STREAM2

Identifier Type: -

Identifier Source: org_study_id