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

Sponsor

KU Leuven (Other)

Overall Status

Recruiting

CT.gov ID

NCT02777580

Collaborator

Boehringer Ingelheim (Industry), Life Sciences Research Partners (Other), Fund for Clinical Cardiovascular Research at LRD (Other)

600

Enrollment

Locations

Arms

Anticipated Duration (Months)

15.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction	Drug: Tenecteplase Drug: Clopidogrel Procedure: Coronary angiography Procedure: Primary PCI	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

600 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

STrategic Reperfusion in Elderly Patients Early After Myocardial Infarction

Actual Study Start Date :

Aug 1, 2017

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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. [30 days]
Serious cardiac events (e.g. death , congestive heart failure, reinfarction, resuscitated ventricular fibrillation, repeat target vessel recanalization, stent thrombosis, total AV block etc).
Composite endpoints (e.g. death, shock, heart failure and recurrent MI) will be assessed as described in the statistical analytical plan. [30 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Informed consent received

Exclusion Criteria:

1. 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
Dementia
Known severe renal insufficiency
Previous enrolment in this study or treatment with an investigational drug or device under another study protocol in the past 7 days
Known allergic reactions to tenecteplase, clopidogrel, enoxaparin and aspirin
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Liverpool Hospital - Cardiology Department	Liverpool		Australia	2170
2	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
3	Hospital Regional de Antofagasta	Antofagasta		Chile	1240801
4	Hospital Comunitario de Mejillones	Mejillones		Chile	1310000
5	Hospital de Melipilla	Melipilla		Chile
6	Hospital Regional de Rancagua	Rancagua		Chile	2820000
7	SAR Rancagua	Rancagua		Chile	2830945
8	Hospital San Juan de Dios	Santiago		Chile	8350488
9	Hospital de Talagante	Talagante		Chile	9670468
10	Hospital de Tocopilla	Tocopilla		Chile	1340000
11	CH Louis Pradel - Hospices civils de Lyon	Bron		France	69677
12	CH Cahors - SAMU 46	Cahors		France	46005
13	CH de Chateauroux	Châteauroux		France	36019
14	CH Sud Francilien - Service Cardiologie	Corbeil-Essonnes		France	91106
15	Centre Hospitalier de Versailles	Le Chesnay		France	78157
16	CHRU de Lille	Lille		France	59037
17	CH St. Joseph - St Luc - Lyon	Lyon		France	69365
18	Groupe Hospitalier Sud Ile de France - CH de Melun - Service SAMU 77	Melun		France
19	Clinque du Pont de Chaume	Montauban		France	82000
20	CH Lucien Hussel	Vienne		France	38209
21	Hospital Gea Gonzalez	Mexico City		Mexico	14080
22	Instituto Nacional de Cardiologia Ignacio Chavez	Mexico City		Mexico	14080
23	Federal State Budgetary Scientific Inst "Tomsk Nat Research Med.Center of Russian Academy Sciences"	Tomsk		Russian Federation	634012
24	Tomsk Regional State Autonomous Healthcare Institution Emergency Care Station	Tomsk		Russian Federation	634059
25	Clinical Center of Serbia, Cardiology Clinic	Belgrade		Serbia	11000
26	Military Medical Academy, Clinic for Emergency Internal Medicine	Belgrade		Serbia	11000
27	Institute for cardiovascular diseases Dedinje, Cardiovascular research sector	Belgrade		Serbia	11040
28	General Hospital Cuprija, Cardiology Department	Cuprija		Serbia	35230
29	General Hospital Jagodina/Intenal Medicine department	Jagodina		Serbia	35000
30	Clinical Center Kragujevac, Cardiology Clinic	Kragujevac		Serbia	34000
31	General Hospital Pancevo/Department of internal medicine - cardiology section	Pančevo		Serbia	26000
32	General Hospital "Sveti Luka" Smederevo, Dept of Internal Med - Cardiology Section	Smederevo		Serbia	11300
33	Institute for cardiovascular diseases Vojvodina - Sremska Kamenica, Cardiology Clinic	Sremska Kamenica		Serbia	21204
34	General Hospital Vrsac/Cardiology department with coronary unit	Vršac		Serbia	26300
35	General Hospital "Dr. Laza K. Lazarevic" Sabac, Internal medicine department	Šabac		Serbia	15000
36	Hospital Virgen de la Victoria, Unidad de Cuidados Intensivos	Málaga		Spain	29010
37	Hospital de Antequera, Unidad de Cuidados Intensivos	Málaga		Spain	29200
38	Hospital Serrania Ronda, Unidad de Cuidados Intensivos	Málaga		Spain	29400
39	Hospital Comarcal Axarquia, Unidad de Cuidados Intensivos	Málaga		Spain	29740

Sponsors and Collaborators

KU Leuven
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