Acute Myocardial Infarction
Conditions
Keywords
Acute myocardial infarction, Reperfusion injury, Nitric oxide
Brief summary
The purpose of this study is to determine whether the intravenous infusion of sodium nitrite safely prevents ischemia-reperfusion injury in subjects with acute myocardial infarction resulting in improved left ventricular function.
Detailed description
Despite reperfusion therapies, significant myocardial injury continues to occur from ischemic-reperfusion injury. Studies in animal models of acute myocardial infarction suggest that an infusion of sodium nitrite, which is nonenzymatically converted to nitric oxide in the setting of ischemia, significantly reduces ischemia-reperfusion injury resulting in smaller infarcts and improved left ventricular function. The objectives of this phase 2 trial are to determine the tolerability and safety of a 48-hour infusion of sodium nitrite in patients with an acute ST-segment elevation myocardial infarction receiving percutaneous coronary intervention. The efficacy of a 48-hour infusion of sodium nitrite will be determined by noninvasive imaging to determine infarct size and left ventricular function.
Interventions
DRUGSodium Nitrite
Subjects assigned to sodium nitrite will receive an initial infusion of 6 nmol/min/kg for 48 hours. After the first six subjects have been enrolled (3 active drug, 3 control) and if there are no dose limiting toxicities, additional cohorts of six subjects each will be randomized to escalating doses of sodium nitrite versus control for a total of 30 subjects.
Sponsors
Hope Pharmaceuticals
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Acute ST segment elevation myocardial infarction * Eligible for percutaneous coronary intervention
Exclusion criteria
* Cardiogenic shock * Cardiac arrest * Prior infarct in the infarct related artery * Hemoglobinopathy, Glucose-6 Phosphate Dehydrogenase (G6PD) deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ischemia Area at Risk as Determined by Paired Single-photon Computed Tomography Studies With Technetium Tc99m Sestamibi. | 4-5 days from enrollment | Measured as percentage of left ventricle |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Infarct Size | 4-5 days following enrollment | Left ventricular infarct size by Magnetic Resonance Imaging (MRI). Calculated percentage of the left ventricular mass by MRI that has undergone infarction. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sodium Nitrite Dose escalation of sodium nitrite.
Sodium Nitrite: Subjects assigned to sodium nitrite will receive an initial infusion of 6 nmol/min/kg for 48 hours. After the first six subjects have been enrolled (3 active drug, 3 control) and if there are no dose limiting toxicities, additional cohorts of six subjects each will be randomized to escalating doses of sodium nitrite versus control for a total of 30 subjects. | 15 |
| Open Control Subjects randomized to open control will receive no experimental therapy. | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Open Control | Sodium Nitrite | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 12 Participants | 23 Participants |
| Age, Continuous | 59.2 years | 59.6 years | 59.4 years |
| Region of Enrollment United States | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 14 Participants | 11 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 4 / 15 | 0 / 15 |
Outcome results
Primary
Ischemia Area at Risk as Determined by Paired Single-photon Computed Tomography Studies With Technetium Tc99m Sestamibi.
Measured as percentage of left ventricle
Time frame: 4-5 days from enrollment
Population: Sestamibi imaging proved impossible to obtain emergently and therefore no data was collected.
Secondary
Left Ventricular Infarct Size
Left ventricular infarct size by Magnetic Resonance Imaging (MRI). Calculated percentage of the left ventricular mass by MRI that has undergone infarction.
Time frame: 4-5 days following enrollment
Population: Only 2 participants from each arm underwent MRI imaging. Too few subjects underwent MRI imaging to make a statistical comparison. Only those where data was obtained has been reported.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sodium Nitrite | Left Ventricular Infarct Size | 15.5 infarct percentage of left ventricle |
| Open Control | Left Ventricular Infarct Size | 24 infarct percentage of left ventricle |