Acute Myocardial Infarction, ST Elevation MI, STEMI
Conditions
Keywords
INOT44, NOMI
Brief summary
The purpose of this study is to assess whether or not inhaled nitric oxide can decrease myocardial infarction (MI) size at 48-72 hours in patients presenting with an ST segment elevation MI (STEMI) who undergo successful percutaneous coronary intervention.
Detailed description
The purpose of the trial is to assess whether or not inhaled nitric oxide can decrease myocardial infarction (MI) size as a fraction of left ventricular (LV) size at 48-72 hours in patients presenting with an ST segment elevation MI who undergo successful percutaneous coronary intervention (PCI). The primary endpoint for this study will be myocardial infarction size as a fraction of left ventricular size at 48-72 hours as measured by contrast-enhanced cardiac MRI.
Interventions
DRUGNitric Oxide
Nitric oxide for inhalation
DRUGPlacebo
Nitrogen gas (placebo) for inhalation
Sponsors
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Acute myocardial infarction and electrocardiographic evidence of ST elevation * No clinical evidence of congestive heart failure * All patients must undergo successful percutaneous coronary intervention for thrombolysis in myocardial infarction (TIMI) 0 or 1 coronary flow with resulting TIMI 2 or 3 flow * Greater than 18 years of age * Signed Institutional Review Board (IRB) approved informed consent
Exclusion criteria
* Prior myocardial infarction * Requirement for urgent cardiac surgery * Previous coronary artery bypass graft (CABG) or primary coronary intervention (PCI) * Left bundle branch block * Heart block that is expected to require a temporary pacemaker for greater than 72 hours * Prior use of thrombolytic therapy for the current event * Unable to tolerate magnetic resonance imaging or unable to tolerate gadolinium contrast media, including patients with a calculated creatinine clearance less than 60 ml/min/1.73m² Body Surface Area (BSA) * Active or recent hemorrhage requiring an invasive procedure for evaluation or transfusion within 6 weeks prior to presentation, or hemorrhagic stroke within the 6 weeks prior * Neutropenia (WBC \<2000 (mm)³), Anemia (HCT \<30%, Thrombocytopenia (Thrombocytes \<50,000 (mm)³). It is not necessary to confirm blood counts prior to start of study drug in the absence of clinical suspicion. * Known or suspected aortic dissection. * Prior history of pulmonary disease requiring chronic oxygen therapy. * Pregnancy, lactating, and women of childbearing potential. * Medical problem likely to preclude completion of the study. * Use of investigational drugs or device within the 30 days prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent of Myocardial Infarction Size to the Fraction of Left Ventricular Size | 48-72 hours | The primary endpoint - mean percent of the myocardial infarction size to the fraction of left ventricular size at 48-72 hours was measured by contrast-enhanced cardiac Magnetic Resonance Imaging (MRI). |
Secondary
| Measure | Time frame |
|---|---|
| MI Size Normalized to Area at Risk | 48-72 hours |
| Myocardial Perfusion at Coronary Angiography | at completion of primary coronary intervention (PCI) |
| Infarct Transmurality | 48-72 hours and 4 months |
| Global & Regional Left Ventricular (LV) Function and LV Mass | 48-72 hours and 4 months |
| Myocardial Infarction (MI) Size at 48-72 Hours | 48-72 hours |
| MI Size as a Fraction of LV Size | 4 months |
| Resolution of ST Segment Elevation Compared With That Observed at Enrollment | 4 hours |
| Troponin T Levels and CPK-MB Area Under the Curve | 48 hours |
| Change in Adverse Remodeling Parameters Compared With 48-72 Hrs: Changes in LV End-diastolic Vol, End-systolic Vol, End-diastolic Myocardial Wall Thickness in Infarct, Peri-infarct and Remote Areas, and in Sphericity Index at End-diastole and End-systole | 4 months |
| Change in Global LV Function and Mass | between 48-72 hours and 4 months |
Countries
Belgium, Canada, United States
Participant flow
Recruitment details
7 medical centers enrolled subjects. A total of 29 subjects were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Nitric Oxide Inhaled Nitric Oxide administered at 80ppm | 13 |
| Nitrogen Gas Nitrogen Gas (Placebo) administered at 80ppm | 16 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Inclusion / exclusion criteria | 5 | 1 |
Baseline characteristics
| Characteristic | Nitrogen Gas | Inhaled Nitric Oxide | 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 | 16 Participants | 13 Participants | 29 Participants |
| Age, Continuous | 63.8 years STANDARD_DEVIATION 12.41 | 62.3 years STANDARD_DEVIATION 11.71 | 63.1 years STANDARD_DEVIATION 11.91 |
| Region of Enrollment United States | 16 participants | 13 participants | 29 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 13 Participants | 8 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 13 | 1 / 16 |
| serious Total, serious adverse events | 1 / 13 | 1 / 16 |
Outcome results
Primary
Mean Percent of Myocardial Infarction Size to the Fraction of Left Ventricular Size
The primary endpoint - mean percent of the myocardial infarction size to the fraction of left ventricular size at 48-72 hours was measured by contrast-enhanced cardiac Magnetic Resonance Imaging (MRI).
Time frame: 48-72 hours
Population: Analysis was per intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Nitric Oxide | Mean Percent of Myocardial Infarction Size to the Fraction of Left Ventricular Size | 15.8 percent of myocardial infarction size | Standard Deviation 8.99 |
| Nitrogen Gas | Mean Percent of Myocardial Infarction Size to the Fraction of Left Ventricular Size | 12.5 percent of myocardial infarction size | Standard Deviation 11.68 |
Secondary
Change in Adverse Remodeling Parameters Compared With 48-72 Hrs: Changes in LV End-diastolic Vol, End-systolic Vol, End-diastolic Myocardial Wall Thickness in Infarct, Peri-infarct and Remote Areas, and in Sphericity Index at End-diastole and End-systole
Time frame: 4 months
Population: All efforts have been exhausted to locate data for this historical trial - the validated summary tables and CSR are no longer accessible.
Secondary
Change in Global LV Function and Mass
Time frame: between 48-72 hours and 4 months
Population: All efforts have been exhausted to locate data for this historical trial - the validated summary tables and CSR are no longer accessible.
Secondary
Global & Regional Left Ventricular (LV) Function and LV Mass
Time frame: 48-72 hours and 4 months
Population: All efforts have been exhausted to locate data for this historical trial - the validated summary tables and CSR are no longer accessible.
Secondary
Infarct Transmurality
Time frame: 48-72 hours and 4 months
Population: All efforts have been exhausted to locate data for this historical trial - the validated summary tables and CSR are no longer accessible.
Secondary
MI Size as a Fraction of LV Size
Time frame: 4 months
Population: All efforts have been exhausted to locate data for this historical trial - the validated summary tables and CSR are no longer accessible.
Secondary
MI Size Normalized to Area at Risk
Time frame: 48-72 hours
Population: All efforts have been exhausted to locate data for this historical trial - the validated summary tables and CSR are no longer accessible.
Secondary
Myocardial Infarction (MI) Size at 48-72 Hours
Time frame: 48-72 hours
Population: All efforts have been exhausted to locate data for this historical trial - the validated summary tables and Clinical Study Report (CSR) are no longer accessible.
Secondary
Myocardial Perfusion at Coronary Angiography
Time frame: at completion of primary coronary intervention (PCI)
Population: All efforts have been exhausted to locate data for this historical trial - the validated summary tables and CSR are no longer accessible.
Secondary
Resolution of ST Segment Elevation Compared With That Observed at Enrollment
Time frame: 4 hours
Population: All efforts have been exhausted to locate data for this historical trial - the validated summary tables and CSR are no longer accessible.
Secondary
Troponin T Levels and CPK-MB Area Under the Curve
Time frame: 48 hours
Population: All efforts have been exhausted to locate data for this historical trial - the validated summary tables and CSR are no longer accessible.