Acute Coronary Syndrome
Conditions
Keywords
Acute Coronary Syndrome, ACS, Percutaneous Coronary Intervention, PCI, Ranolazine, Coronary Angiogram, Cardioprotectant
Brief summary
The investigators will test if upfront dosing of Ranolazine can reduce myocardial biomarker release (CK-MB, Troponin) post percutaneous coronary intervention (PCI).
Detailed description
Ranolazine has been demonstrated to decrease angina, ischemia on perfusion imaging, improve diastolic function, and cardiac metabolism. Furthermore it has been associated with reduced cardiac arrhythmias, including non-sustained ventricular tachycardia and atrial fibrillation. It has not been studied as an acute cardioprotective agent in percutaneous coronary intervention (PCI). We hypothesize that upfront administration of Ranolazine could decrease the myocardial injury associated with PCI due to all the factors listed above (i.e. precondition the myocardium). We plan to screen all patients scheduled for an elective coronary angiogram. Those who meet criteria and consent will be randomized to either receive Ranolazine or placebo twice a day for 3 days leading up to the PCI.
Interventions
DRUGPlacebo
Drug: Placebo Oral dose twice per day for 3 days leading up to PCI
DRUGRanolazine
Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI
Sponsors
Gilead Sciences
Harvey Hahn
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 or older * Patients undergoing Coronary Angiography with possible PCI * Able and willing to give consent * Able to read and write English
Exclusion criteria
* Current EKG or Biomarker of Acute Myocardial Infarction (MI) or Acute Coronary Syndromes (ACS) * History of Allergy to Ranolazine * Pregnant or Nursing * Currently taking Ranolazine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Troponin | 8-10 hrs post PCI | Troponin labs will be drawn 8-10 hrs after PCI or at discharge whichever comes first |
| CK-MB | 8-10 hrs post PCI | CK-MB labs will be drawn 8-10 hrs after PCI or at discharge whichever comes first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Non-sustained Ventricular Tachycardia or Atrial Fibrillation Post PCI | Following completion of PCI through hospital discharge | — |
| Left Ventricular End Diastolic Pressure (LVEDP) | During the PCI (Percutaneous Coronary Intervention) procedure - starting at timepoint of guidewire insertion into the access artery until removal of guidewire | — |
| TIMI Flow Rate (Grade) | TIMI Flow Rate (Grade) is assessed immediately after an interventional reperfusion attempt during a PCI (Percutaneous Coronary Intervention) procedure. | This TIMI classification was developed by the TIMI (Thrombolysis In Myocardial Infarction) study group to semiquantitatively assess coronary artery perfusion beyond point of occlusion on coronary angiography.\* TIMI Grade \[Description\] TIMI 0 - no perfusion \[no antegrade flow beyond the point of occlusion\] TIMI 1 - penetration without perfusion \[faint antegrade coronary flow beyond the occlusion with incomplete filling of the distal coronary bed\] TIMI 2 - partial perfusion \[delayed or sluggish antegrade flow with complete filling of the distal territory\] TIMI 3 - complete perfusion \[normal flow with complete filling of the distal territory\] \*(see http://radclass.mudr.org/content/timi-grade-flow-grading-coronary-blood-flow-during-coronary-angiography) TIMI 0 is the least favorable grade. TIMI 3 is the most favorable grade. |
| Death, MI, Revascularization, CHF | 1-4 weeks post PCI | — |
| Successful PCI | At discharge or within 1 days, whichever comes first | For the purposes of this study, a successful PCI is considered one where no additional coronary interventions were required within 24 hours after the initial PCI. |
| Death, Myocardial Infarction (Biomarker Greater Than 2x Normal), CHF, Cardiac Arrest | At discharge or within 1 days, whichever comes first | — |
| Incidence of Atrial Fibrillation, Ventricular Tachycardia, or Ventricular Fibrillation in Coronary Cath Lab | During the PCI (Percutaneous Coronary Intervention) procedure - starting at timepoint of guidewire insertion into the access artery until removal of guidewire | Abnormal heart activity |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ranolazine Oral treatment Intervention: Drug: Ranolazine 1000 mg
Ranolazine: Drug: Ranolazine 1000 mg Oral dose twice per day for 3 days leading up to PCI | 4 |
| Placebo Oral treatment Intervention: Drug: Placebo
Placebo: Drug: Placebo Oral dose twice per day for 3 days leading up to PCI | 2 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 4 | 1 |
Baseline characteristics
| Characteristic | Ranolazine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Continuous | 61.5 years | 67.5 years | 63.5 years |
| Region of Enrollment United States | 4 participants | 2 participants | 6 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 2 |
| serious Total, serious adverse events | 0 / 4 | 0 / 2 |
Outcome results
Primary
CK-MB
CK-MB labs will be drawn 8-10 hrs after PCI or at discharge whichever comes first
Time frame: 8-10 hrs post PCI
Population: For the single subject completing the PCI intervention, CK-MB was not done because the CK level was below the threshold running the CK-MB test.
Primary
Troponin
Troponin labs will be drawn 8-10 hrs after PCI or at discharge whichever comes first
Time frame: 8-10 hrs post PCI
Population: Of the 4 Ranolazine Group subjects, 1 was withdrawn for pre-procedure study drug non-compliance; 3 had no PCI intervention. Of the 2 Placebo Group subject, 1 had no PCI intervention. The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject undergoing this protocol required test.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Troponin | 0.023 NG/ML |
Secondary
Death, MI, Revascularization, CHF
Time frame: 1-4 weeks post PCI
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Death, MI, Revascularization, CHF | 0 participants |
Secondary
Death, Myocardial Infarction (Biomarker Greater Than 2x Normal), CHF, Cardiac Arrest
Time frame: At discharge or within 1 days, whichever comes first
Population: The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject for whom these protocol required data points were collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Death, Myocardial Infarction (Biomarker Greater Than 2x Normal), CHF, Cardiac Arrest | 0 participants |
Secondary
Incidence of Atrial Fibrillation, Ventricular Tachycardia, or Ventricular Fibrillation in Coronary Cath Lab
Abnormal heart activity
Time frame: During the PCI (Percutaneous Coronary Intervention) procedure - starting at timepoint of guidewire insertion into the access artery until removal of guidewire
Population: The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject for whom these protocol required data points were collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence of Atrial Fibrillation, Ventricular Tachycardia, or Ventricular Fibrillation in Coronary Cath Lab | 0 participants |
Secondary
Incidence of Non-sustained Ventricular Tachycardia or Atrial Fibrillation Post PCI
Time frame: Following completion of PCI through hospital discharge
Population: The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject for whom these protocol required data points were collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence of Non-sustained Ventricular Tachycardia or Atrial Fibrillation Post PCI | 0 participants |
Secondary
Left Ventricular End Diastolic Pressure (LVEDP)
Time frame: During the PCI (Percutaneous Coronary Intervention) procedure - starting at timepoint of guidewire insertion into the access artery until removal of guidewire
Population: The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject for whom this protocol required data point was collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Left Ventricular End Diastolic Pressure (LVEDP) | 10 mmHG |
Secondary
Successful PCI
For the purposes of this study, a successful PCI is considered one where no additional coronary interventions were required within 24 hours after the initial PCI.
Time frame: At discharge or within 1 days, whichever comes first
Population: The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject for whom these protocol required data points were collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Successful PCI | 1 participants |
Secondary
TIMI Flow Rate (Grade)
This TIMI classification was developed by the TIMI (Thrombolysis In Myocardial Infarction) study group to semiquantitatively assess coronary artery perfusion beyond point of occlusion on coronary angiography.\* TIMI Grade \[Description\] TIMI 0 - no perfusion \[no antegrade flow beyond the point of occlusion\] TIMI 1 - penetration without perfusion \[faint antegrade coronary flow beyond the occlusion with incomplete filling of the distal coronary bed\] TIMI 2 - partial perfusion \[delayed or sluggish antegrade flow with complete filling of the distal territory\] TIMI 3 - complete perfusion \[normal flow with complete filling of the distal territory\] \*(see http://radclass.mudr.org/content/timi-grade-flow-grading-coronary-blood-flow-during-coronary-angiography) TIMI 0 is the least favorable grade. TIMI 3 is the most favorable grade.
Time frame: TIMI Flow Rate (Grade) is assessed immediately after an interventional reperfusion attempt during a PCI (Percutaneous Coronary Intervention) procedure.
Population: The only subject undergoing PCI intervention was from the Placebo Group and was thus the only subject for whom this protocol required data point was collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | TIMI Flow Rate (Grade) | 3 units on a scale |