Myocardial Infarction
Conditions
Keywords
Thrombolytic Therapy, Primary PCI
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.
Interventions
DRUGTenecteplase
Half dose Tenecteplase
DRUGClopidogrel
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.
PROCEDURECoronary angiography
Coronary angiography followed by PCI or CABG if required, rescue PCI if required
PROCEDUREPrimary PCI
Primary PCI accoring to local standards
Sponsors
Boehringer Ingelheim
Life Sciences Research Partners
Frans Van de Werf Fund for Clinical Cardiovascular Research
KU Leuven
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Successful Reperfusion | 30 min post angiogram/PCI | Worst-lead ST-segment elevation resolution ≥ 50% 30 min post angiogram/PCI |
| Composite Clinical Efficacy End Point: All Cause Death, Shock, CHF and Reinfarction at 30 Days | 30 days | — |
| Total Stroke | 30 days | Number of patients with stroke (intracranial haemorrhage, ischaemic, haemorrhagic conversion) |
| Major Non-intrancranial Bleedings | 30 days | — |
Countries
Australia, Brazil, Canada, Chile, France, Mexico, Montenegro, Russia, Serbia, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Tenecteplase: Half dose Tenecteplase
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.
Coronary angiography: Coronary angiography followed by PCI or CABG if required, rescue PCI if required | 401 |
| Standard Primary PCI Primary PCI with a P2Y12 antagonist and antithrombin treatment according to local standards.
Primary PCI: Primary PCI accoring to local standards | 203 |
| Total | 604 |
Baseline characteristics
| Characteristic | Pharmaco-invasive Strategy | Standard Primary PCI | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 288 Participants | 156 Participants | 444 Participants |
| Age, Categorical Between 18 and 65 years | 113 Participants | 47 Participants | 160 Participants |
| Age, Continuous | 70 years STANDARD_DEVIATION 8 | 71 years STANDARD_DEVIATION 8 | 70 years STANDARD_DEVIATION 8 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Australia | 6 participants | 3 participants | 9 participants |
| Region of Enrollment Brazil | 14 participants | 6 participants | 20 participants |
| Region of Enrollment Canada | 66 participants | 34 participants | 100 participants |
| Region of Enrollment Chile | 10 participants | 5 participants | 15 participants |
| Region of Enrollment France | 28 participants | 14 participants | 42 participants |
| Region of Enrollment Mexico | 53 participants | 28 participants | 81 participants |
| Region of Enrollment Montenegro | 5 participants | 3 participants | 8 participants |
| Region of Enrollment Russia | 95 participants | 47 participants | 142 participants |
| Region of Enrollment Serbia | 117 participants | 60 participants | 177 participants |
| Region of Enrollment Spain | 7 participants | 3 participants | 10 participants |
| Sex: Female, Male Female | 131 Participants | 66 Participants | 197 Participants |
| Sex: Female, Male Male | 270 Participants | 137 Participants | 407 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 37 / 401 | 18 / 203 |
| other Total, other adverse events | 0 / 401 | 0 / 203 |
| serious Total, serious adverse events | 69 / 401 | 32 / 203 |
Outcome results
Primary
Composite Clinical Efficacy End Point: All Cause Death, Shock, CHF and Reinfarction at 30 Days
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pharmaco-invasive Strategy | Composite Clinical Efficacy End Point: All Cause Death, Shock, CHF and Reinfarction at 30 Days | 51 Participants |
| Standard Primary PCI | Composite Clinical Efficacy End Point: All Cause Death, Shock, CHF and Reinfarction at 30 Days | 27 Participants |
95% CI: [0.62, 1.48]
Primary
Major Non-intrancranial Bleedings
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pharmaco-invasive Strategy | Major Non-intrancranial Bleedings | 5 Participants |
| Standard Primary PCI | Major Non-intrancranial Bleedings | 2 Participants |
95% CI: [0.25, 6.48]
Primary
Successful Reperfusion
Worst-lead ST-segment elevation resolution ≥ 50% 30 min post angiogram/PCI
Time frame: 30 min post angiogram/PCI
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pharmaco-invasive Strategy | Successful Reperfusion | 305 Participants |
| Standard Primary PCI | Successful Reperfusion | 149 Participants |
p-value: 0.05Chi-squared
Primary
Total Stroke
Number of patients with stroke (intracranial haemorrhage, ischaemic, haemorrhagic conversion)
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pharmaco-invasive Strategy | Total Stroke | 9 Participants |
| Standard Primary PCI | Total Stroke | 1 Participants |
95% CI: [0.58, 35.8]