Myocardial Infarction
Conditions
Keywords
STEMI, ACS
Brief summary
Safety and efficacy of adjunctive antiplatelet therapy prior to primary percutaneous intervention (PCI) in patients with ST-Elevation Myocardial Infarction (STEMI)
Detailed description
Patients with STEMI who are to undergo primary PCI will be randomized to an intravenous (iv) bolus of placebo vs. PRT060128 prior to angiography.
Interventions
DRUGplacebo
administration of iv bolus prior to angiography
DRUGPRT060128 Potassium
administration of iv bolus prior to angiography
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Persistent ST elevation ≥ 1mm (≥ 0.1mV) in two contiguous limb leads OR ≥ 2 mm (≥ 0.2mV) in two contiguous precordial leads, AND chest pain ≥ 20 minutes with onset within 6 hours of hospital presentation.
Exclusion criteria
* Cardiogenic shock (systolic blood pressure \< 90 mm Hg requiring vasopressor or hemodynamic support) * Uncontrolled hypertension defined as any measured systolic blood pressure (SBP) \> 180 mm Hg or diastolic blood pressure (DBP) ≥ 110 mm Hg after the time -- History or symptoms of a congenital or acquired bleeding disorder or vascular malformation. * Recent gastrointestinal bleeding within the last 30 days. * Known thrombocytopenia (platelet count \< 100,000/mm3). * Any treatment with a fibrinolytic agent within the last 7 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Thrombolysis in Myocardial Infarction (TIMI) Major/Minor Bleeding, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/Moderate Bleeding Through Hospital Discharge, and Intracranial Hemorrhage Through 30 Days | 30 days | TIMI Major:Intracranial bleeding or a decrease in the hemoglobin concentration of 5g/dL or more, or 15% or greater decrease in hematocrit. TIMI Minor:Hemoglobin concentration decreased by 3g/dL (but \<5g/dL) or the hematocrit decreased by 10-15%. GUSTO Severe/life threatening:Intracranial hemorrhage or bleeding that causes hemodynamic compromise requiring intervention. GUSTO Moderate:Bleeding that requires bloodtransfusion but does not lead to hemodynamic compromise requiring intervention. Stroke:New focal neurologic deficit that does not resolve within 24 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Corrected TIMI Frame Count (cTFC) in the Infarct Artery on the Initial Diagnostic Angiogram Before Primary PCI | Time for contrast to reach a standardized distal coronary landmark in the culprit vessel | This measure was used to assess flow in the epicardial artery. It is the number of cine frames required for contrast to reach a standardized distal coronary landmark in the culprit vessel and was to be counted using an electronic frame counter. |
| Percentage ST-segment Resolution Prior to PCI | Before primary PCI | The relative effect of PRT060128 on ST-segment measured after PCI and expressed as a percent of ST-Segment prior to PCI. This measure was used to evaluate the dethrombotic and early reperfusion effects of PRT060128 in STEMI. |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORMatthew T. Roe, MD, MHS
Duke Clinical Research Institute
PRINCIPAL_INVESTIGATORMichael Gibson, MD, MS
PERFUSE Angiographic Core Laboratory and Data Coordinating Center
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo Comparator | 36 |
| Experimental Experimental Cohorts (10, 20, 40, 60 mg) | 34 |
| Total | 70 |
Baseline characteristics
| Characteristic | Placebo | Experimental | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 34 Participants | 70 Participants |
| Age, Continuous | 53.6 years STANDARD_DEVIATION 11.9 | 57.8 years STANDARD_DEVIATION 10.4 | 55.6 years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 29 Participants | 29 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| other Total, other adverse events | 15 / 36 | 21 / 34 |
| serious Total, serious adverse events | 8 / 36 | 2 / 34 |
Outcome results
Primary
Number of Patients With Thrombolysis in Myocardial Infarction (TIMI) Major/Minor Bleeding, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/Moderate Bleeding Through Hospital Discharge, and Intracranial Hemorrhage Through 30 Days
TIMI Major:Intracranial bleeding or a decrease in the hemoglobin concentration of 5g/dL or more, or 15% or greater decrease in hematocrit. TIMI Minor:Hemoglobin concentration decreased by 3g/dL (but \<5g/dL) or the hematocrit decreased by 10-15%. GUSTO Severe/life threatening:Intracranial hemorrhage or bleeding that causes hemodynamic compromise requiring intervention. GUSTO Moderate:Bleeding that requires bloodtransfusion but does not lead to hemodynamic compromise requiring intervention. Stroke:New focal neurologic deficit that does not resolve within 24 hours.
Time frame: 30 days
Population: All subjects receiving some component of study drug (the as-treated population)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Patients With Thrombolysis in Myocardial Infarction (TIMI) Major/Minor Bleeding, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/Moderate Bleeding Through Hospital Discharge, and Intracranial Hemorrhage Through 30 Days | Dose 10 mg | 3 Participants |
| Placebo | Number of Patients With Thrombolysis in Myocardial Infarction (TIMI) Major/Minor Bleeding, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/Moderate Bleeding Through Hospital Discharge, and Intracranial Hemorrhage Through 30 Days | Dose 20 mg | 1 Participants |
| Placebo | Number of Patients With Thrombolysis in Myocardial Infarction (TIMI) Major/Minor Bleeding, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/Moderate Bleeding Through Hospital Discharge, and Intracranial Hemorrhage Through 30 Days | Dose 40 mg | 4 Participants |
| Placebo | Number of Patients With Thrombolysis in Myocardial Infarction (TIMI) Major/Minor Bleeding, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/Moderate Bleeding Through Hospital Discharge, and Intracranial Hemorrhage Through 30 Days | Dose 60 mg | 3 Participants |
| Experimental | Number of Patients With Thrombolysis in Myocardial Infarction (TIMI) Major/Minor Bleeding, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/Moderate Bleeding Through Hospital Discharge, and Intracranial Hemorrhage Through 30 Days | Dose 60 mg | 0 Participants |
| Experimental | Number of Patients With Thrombolysis in Myocardial Infarction (TIMI) Major/Minor Bleeding, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/Moderate Bleeding Through Hospital Discharge, and Intracranial Hemorrhage Through 30 Days | Dose 10 mg | 2 Participants |
| Experimental | Number of Patients With Thrombolysis in Myocardial Infarction (TIMI) Major/Minor Bleeding, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/Moderate Bleeding Through Hospital Discharge, and Intracranial Hemorrhage Through 30 Days | Dose 40 mg | 4 Participants |
| Experimental | Number of Patients With Thrombolysis in Myocardial Infarction (TIMI) Major/Minor Bleeding, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/Moderate Bleeding Through Hospital Discharge, and Intracranial Hemorrhage Through 30 Days | Dose 20 mg | 0 Participants |
Secondary
Corrected TIMI Frame Count (cTFC) in the Infarct Artery on the Initial Diagnostic Angiogram Before Primary PCI
This measure was used to assess flow in the epicardial artery. It is the number of cine frames required for contrast to reach a standardized distal coronary landmark in the culprit vessel and was to be counted using an electronic frame counter.
Time frame: Time for contrast to reach a standardized distal coronary landmark in the culprit vessel
Population: Per protocol
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Corrected TIMI Frame Count (cTFC) in the Infarct Artery on the Initial Diagnostic Angiogram Before Primary PCI | Dose 10 mg | 42 frames per minute |
| Placebo | Corrected TIMI Frame Count (cTFC) in the Infarct Artery on the Initial Diagnostic Angiogram Before Primary PCI | Dose 20 mg | 100 frames per minute |
| Placebo | Corrected TIMI Frame Count (cTFC) in the Infarct Artery on the Initial Diagnostic Angiogram Before Primary PCI | Dose 40 mg | 100 frames per minute |
| Placebo | Corrected TIMI Frame Count (cTFC) in the Infarct Artery on the Initial Diagnostic Angiogram Before Primary PCI | Dose 60 mg | 100 frames per minute |
| Experimental | Corrected TIMI Frame Count (cTFC) in the Infarct Artery on the Initial Diagnostic Angiogram Before Primary PCI | Dose 60 mg | 100 frames per minute |
| Experimental | Corrected TIMI Frame Count (cTFC) in the Infarct Artery on the Initial Diagnostic Angiogram Before Primary PCI | Dose 10 mg | 59 frames per minute |
| Experimental | Corrected TIMI Frame Count (cTFC) in the Infarct Artery on the Initial Diagnostic Angiogram Before Primary PCI | Dose 40 mg | 100 frames per minute |
| Experimental | Corrected TIMI Frame Count (cTFC) in the Infarct Artery on the Initial Diagnostic Angiogram Before Primary PCI | Dose 20 mg | 100 frames per minute |
Secondary
Percentage ST-segment Resolution Prior to PCI
The relative effect of PRT060128 on ST-segment measured after PCI and expressed as a percent of ST-Segment prior to PCI. This measure was used to evaluate the dethrombotic and early reperfusion effects of PRT060128 in STEMI.
Time frame: Before primary PCI
Population: Per protocol.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Percentage ST-segment Resolution Prior to PCI | Dose 10 mg | 82.8 Percentage of ST-segment Resolution |
| Placebo | Percentage ST-segment Resolution Prior to PCI | Dose 20 mg | 72.4 Percentage of ST-segment Resolution |
| Placebo | Percentage ST-segment Resolution Prior to PCI | Dose 40 mg | 75.3 Percentage of ST-segment Resolution |
| Placebo | Percentage ST-segment Resolution Prior to PCI | Dose 60 mg | 77.6 Percentage of ST-segment Resolution |
| Experimental | Percentage ST-segment Resolution Prior to PCI | Dose 60 mg | 71.5 Percentage of ST-segment Resolution |
| Experimental | Percentage ST-segment Resolution Prior to PCI | Dose 10 mg | 65 Percentage of ST-segment Resolution |
| Experimental | Percentage ST-segment Resolution Prior to PCI | Dose 40 mg | 37.9 Percentage of ST-segment Resolution |
| Experimental | Percentage ST-segment Resolution Prior to PCI | Dose 20 mg | 86.5 Percentage of ST-segment Resolution |