Acute ST Elevation Myocardial Infarction
Conditions
Keywords
ST elevation myocardial infarction, Primary percutaneous coronary intervention, Unfractionated heparin, Bivalirudin, primary angioplasty
Brief summary
The purpose of this study is to compare unfractionated heparin (UFH) and bivalirudin in the performance and subsequent outcomes of Primary percutaneous coronary intervention. This will be a pragmatic trial. Interventional procedures will be performed to reflect current and evolving standards, including predominant radial access. All patients will be treated with routine oral anti-platelet therapy pre-procedure. GP IIb/IIIa inhibitors will be reserved for 'bail out' treatment only.
Detailed description
HEAT-PPCI is a single-centre prospective, dual-arm, open-label, randomised controlled trial comparing two antithrombotic agents in patients undergoing PPCI. All patients presenting to the PPCI service at Liverpool Heart and Chest Hospital will be assessed for trial eligibility. The patients will be allocated by randomisation in equal proportions to the two treatment groups receiving UFH (70 units/kg prior to the procedure) or bivalirudin (bolus of 0.75 mg/kg prior to the start of the intervention, followed by an infusion of 1.75 mg/kg per hour for the duration of the procedure). Pre-Specified Subgroup Analyses * Subgroup analyses looking at the impact of access site comparing radial versus femoral route * Assessment of the outcomes in diabetic patients receiving oral hypoglycaemic or insulin therapy versus all other patients * Comparing the outcomes in patients \< or ≥ 75 years of age * Type of p2y12 receptor inhibiting antiplatelet agent (Examples: clopidogrel, prasugrel, ticagrelor) * Patients with impaired LV function versus normal LV function * Patients managed with actual or attempted primary PCI versus no immediate PCI procedure attempted PLATELET FUNCTION SUBSTUDY A substudy will be performed to assess indices of coagulation and platelet function studies comparing the impact of heparin or bivalirudin therapy on coagulation status at the end of the PPCI procedure. This study will be performed on all patients treated between the hours of 0800 and 1600, Monday to Friday. A single blood sample taken at the time of general blood sampling for routine clinical screening will be analysed.
Interventions
DRUGunfractionated heparin
70 units/kg body weight intravenous
DRUGBivalirudin
intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour
Sponsors
Liverpool Heart and Chest Hospital NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All patients presenting with a suspected myocardial infarction event with PPCI as the proposed index reperfusion strategy will be included in the trial
Exclusion criteria
* ≤ 18 years of age * Known intolerance, hypersensitivity or contraindication to any trial medication * Active bleeding at presentation * Artificial ventilation, reduced conscious level or other factors precluding the administration of oral antiplatelet therapy * Previous enrolment in this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Major Adverse Cardiac Events (MACE) in Terms of the Incidence of All Cause Mortality, Cerebrovascular Accident, Re-infarction and Additional Unplanned Target Lesion Revascularization | 28 days |
| Type 3-5 Bleeding According to BARC (Bleeding Academic Research Consortium)Definition | 28 days |
Secondary
| Measure | Time frame |
|---|---|
| Stent Thrombosis Rate (ARC Definite or Probable) | 28 days |
| For Illustration, and to Allow Comparison With Existing Trials the Rate of Net Adverse Clinical Events (NACE), Combining the Primary Safety and Efficacy Outcomes | 28 days |
| CKMB Release Following Index Revascularisation Measured With a Single Estimation 12-18 Hours After the Procedure | 28 days |
| Development of Thrombocytopenia | 28 days |
| Door-to-first Device Time | 28 days |
| All Cause Mortality | 1 year |
| Minor Bleeding: Type 2 Bleeding According to BARC (Bleeding Academic Research Consortium) Definition | 28 days |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Unfractionated Heparin 70 units/kg body weight intravenous
unfractionated heparin: 70 units/kg body weight intravenous | 907 |
| Bivalirudin intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour
Bivalirudin: intravenous bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg per hour | 905 |
| Total | 1,812 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Consent not available | 7 | 10 |
Baseline characteristics
| Characteristic | Unfractionated Heparin | Bivalirudin | Total |
|---|---|---|---|
| Age, Continuous | 63.6 years | 62.9 years | 63.2 years |
| Sex: Female, Male Female | 244 Participants | 258 Participants | 502 Participants |
| Sex: Female, Male Male | 663 Participants | 647 Participants | 1310 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Major Adverse Cardiac Events (MACE) in Terms of the Incidence of All Cause Mortality, Cerebrovascular Accident, Re-infarction and Additional Unplanned Target Lesion Revascularization
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Unfractionated Heparin | Major Adverse Cardiac Events (MACE) in Terms of the Incidence of All Cause Mortality, Cerebrovascular Accident, Re-infarction and Additional Unplanned Target Lesion Revascularization | 5.7 percentage of total participants |
| Bivalirudin | Major Adverse Cardiac Events (MACE) in Terms of the Incidence of All Cause Mortality, Cerebrovascular Accident, Re-infarction and Additional Unplanned Target Lesion Revascularization | 8.7 percentage of total participants |
Primary
Type 3-5 Bleeding According to BARC (Bleeding Academic Research Consortium)Definition
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Unfractionated Heparin | Type 3-5 Bleeding According to BARC (Bleeding Academic Research Consortium)Definition | 3.1 percentage of total participants |
| Bivalirudin | Type 3-5 Bleeding According to BARC (Bleeding Academic Research Consortium)Definition | 3.5 percentage of total participants |
Secondary
All Cause Mortality
Time frame: 1 year
Secondary
CKMB Release Following Index Revascularisation Measured With a Single Estimation 12-18 Hours After the Procedure
Time frame: 28 days
Secondary
Development of Thrombocytopenia
Time frame: 28 days
Secondary
Door-to-first Device Time
Time frame: 28 days
Secondary
For Illustration, and to Allow Comparison With Existing Trials the Rate of Net Adverse Clinical Events (NACE), Combining the Primary Safety and Efficacy Outcomes
Time frame: 28 days
Secondary
Minor Bleeding: Type 2 Bleeding According to BARC (Bleeding Academic Research Consortium) Definition
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Unfractionated Heparin | Minor Bleeding: Type 2 Bleeding According to BARC (Bleeding Academic Research Consortium) Definition | 10.8 percentage of total participants |
| Bivalirudin | Minor Bleeding: Type 2 Bleeding According to BARC (Bleeding Academic Research Consortium) Definition | 9.2 percentage of total participants |
Secondary
Stent Thrombosis Rate (ARC Definite or Probable)
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Unfractionated Heparin | Stent Thrombosis Rate (ARC Definite or Probable) | 0.9 percentage of total participants |
| Bivalirudin | Stent Thrombosis Rate (ARC Definite or Probable) | 3.4 percentage of total participants |