Acute Myocardial Infarction
Conditions
Brief summary
The purpose of this study is to determine the efficacy of intravenous human beta natriuretic peptide (BNP, Nesiritide) as compared to placebo to prevent adverse post acute myocardial infarction left ventricular remodeling.
Detailed description
Post acute myocardial infarction (AMI) left ventricular (LV) remodeling begins within hours of the acute event with permanent consequences. Previous studies have demonstrated that LV remodeling is one of the major determinants of long-term survival post AMI. Recent studies have reported that the cardiac natriuretic peptides, atrial natriuretic peptide (ANP) and BNP have direct anti-fibrotic and anti-proliferative effects on the myocardium. More importantly, it has been reported that in the acute phase of AMI, the secretion of the cardiac natriuretic peptides may be insufficient relative to the chronic phase. Therefore, augmentation of the cardiac natriuretic peptide system, such as by exogenous administration of exogenous peptide may prevent post AMI LV remodeling because of the cardioprotective effects. The objective of this study is to to determine the efficacy of IV human BNP (Nesiritide) as compared to placebo to prevent adverse post AMI LV remodeling. This is a randomized double blinded placebo controlled study to determine efficacy of 72 hours of IV BNP at 0.006µg/Kg/min as compared to placebo in patients with anterior ST-elevation myocardial infarction and successful revascularization. The study population will include 60 patients admitted to the Cardiac Care Unit with a first anterior AMI and successful reperfusion therapy (TIMI grade 3 flow) within 24 hours of onset of chest pain documented by coronary angiography.
Interventions
DRUGNesiritide
Infusion of 72 hours of IV nesiritide at 0.006 mcg/kg/min.
DRUGPlacebo
Infusion of 72 hours of saline solution (packaged to match active comparator)
Sponsors
Mayo Clinic
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
* Patients with acute ST elevation myocardial infarction with \> or = 2 mm ST elevation in one or any combination of anterior leads, with successful revascularization (TIMI grade 3 flow) of the lesion within 24 hours of symptoms and consented within 24 hours of procedure.
Exclusion criteria
* Cardiogenic shock or hypotension, Systolic BP\< 90 mmHg or overt Congestive Heart Failure (CHF) * Previous history of MI (Myocardial Infarction) * Previous ECG suggesting previous MI * Known Ejection Fraction (EF) \< 30% * Atrial fibrillation * Previously known significant valvular disease (Grade III, IV), cardiomyopathy and congenital heart disease. * Hemoglobin \<10 mg/dL * Pregnant women/nursing mothers * Participants still menstruating and have not been surgically sterilized must have a negative pregnancy test prior to participating in this study. * Unable to undergo cardiac MRI (Magnetic Resonance Imaging). * Contraindications to MRI include pacemaker or defibrillator, pregnant women, atrial fibrillation or other arrhythmia, cerebral aneurysm clips or severe claustrophobia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Left Ventricular End-Systolic Volume Index | baseline, 30 days | Change in Left Ventricular end-systolic volume index as determined by Multiple Gated Acquisition (MUGA) scan from baseline to 30 days. The MUGA scan is a noninvasive tool for assessing the function of the heart. The MUGA scan produces a moving image of the beating heart, and from this image several important features can be determined about the health of the cardiac ventricles (the heart's major pumping chambers). End-systolic volume (ESV) is the volume of blood in a ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. ESV is the lowest volume of blood in the ventricle at any point in the cardiac cycle and can be used clinically as a measurement of the adequacy of cardiac emptying, related to systolic function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Left Ventricular End-Systolic Diastolic Volume Index | baseline, 30 days | Change in Left Ventricular end-systolic diastolic volume index determined by Multiple Gated Acquisition (MUGA) scan from baseline to 30 days. The MUGA scan is a noninvasive tool for assessing the function of the heart. The MUGA scan produces a moving image of the beating heart, and from this image several important features can be determined about the health of the cardiac ventricles (the heart's major pumping chambers). End-systolic volume (ESV) is the volume of blood in a ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. ESV is the lowest volume of blood in the ventricle at any point in the cardiac cycle and can be used clinically as a measurement of the adequacy of cardiac emptying, related to systolic function. |
| Myocardial Infarct Size at 30 Days | 30 days | Myocardial infarction or acute myocardial infarction (AMI) is the medical term for an event commonly known as a heart attack. Myocardial (heart muscle) infarction is tissue death (also known as necrosis) caused by a local lack of oxygen, due to an obstruction of the tissue's blood supply. The resulting heart tissue lesion is referred to as an infarct. A larger size or area of infarct indicates a greater amount of heart tissue death. Myocardial infarct size was measured using a cardiac Magnetic Resonance Imaging (MRI) scan at 30 days and is the mass of the infarcted tissue divided by the mass of the left ventricle times 100%. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited at the Mayo Clinic Cardiac Care Units in Rochester, Minnesota and Jacksonville, Florida.
Pre-assignment details
One subject withdrew consent before randomization.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Infusion of 72 hours of saline solution (packaged to match active comparator). | 28 |
| Nesiritide Infusion of 72 hours of IV nesiritide at 0.006 mcg/kg/min. | 25 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Placebo | Nesiritide | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 8 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 17 Participants | 39 Participants |
| Age, Continuous | 55.85 years STANDARD_DEVIATION 11.12 | 60.4 years STANDARD_DEVIATION 11.15 | 58.0 years STANDARD_DEVIATION 11.26 |
| Region of Enrollment United States | 28 participants | 25 participants | 53 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 25 Participants | 22 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 28 | 13 / 25 |
| serious Total, serious adverse events | 5 / 28 | 1 / 25 |
Outcome results
Primary
Change in Left Ventricular End-Systolic Volume Index
Change in Left Ventricular end-systolic volume index as determined by Multiple Gated Acquisition (MUGA) scan from baseline to 30 days. The MUGA scan is a noninvasive tool for assessing the function of the heart. The MUGA scan produces a moving image of the beating heart, and from this image several important features can be determined about the health of the cardiac ventricles (the heart's major pumping chambers). End-systolic volume (ESV) is the volume of blood in a ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. ESV is the lowest volume of blood in the ventricle at any point in the cardiac cycle and can be used clinically as a measurement of the adequacy of cardiac emptying, related to systolic function.
Time frame: baseline, 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Left Ventricular End-Systolic Volume Index | -2.1 mL of blood/meter^2 body surface area | Standard Deviation 58 |
| Nesiritide | Change in Left Ventricular End-Systolic Volume Index | -4.6 mL of blood/meter^2 body surface area | Standard Deviation 31 |
p-value: 0.97t-test, 2 sided
Secondary
Change in Left Ventricular End-Systolic Diastolic Volume Index
Change in Left Ventricular end-systolic diastolic volume index determined by Multiple Gated Acquisition (MUGA) scan from baseline to 30 days. The MUGA scan is a noninvasive tool for assessing the function of the heart. The MUGA scan produces a moving image of the beating heart, and from this image several important features can be determined about the health of the cardiac ventricles (the heart's major pumping chambers). End-systolic volume (ESV) is the volume of blood in a ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. ESV is the lowest volume of blood in the ventricle at any point in the cardiac cycle and can be used clinically as a measurement of the adequacy of cardiac emptying, related to systolic function.
Time frame: baseline, 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Left Ventricular End-Systolic Diastolic Volume Index | 4.4 mL blood/meter^2 body surface area | Standard Deviation 88 |
| Nesiritide | Change in Left Ventricular End-Systolic Diastolic Volume Index | 9.7 mL blood/meter^2 body surface area | Standard Deviation 51 |
p-value: 0.35t-test, 2 sided
Secondary
Myocardial Infarct Size at 30 Days
Myocardial infarction or acute myocardial infarction (AMI) is the medical term for an event commonly known as a heart attack. Myocardial (heart muscle) infarction is tissue death (also known as necrosis) caused by a local lack of oxygen, due to an obstruction of the tissue's blood supply. The resulting heart tissue lesion is referred to as an infarct. A larger size or area of infarct indicates a greater amount of heart tissue death. Myocardial infarct size was measured using a cardiac Magnetic Resonance Imaging (MRI) scan at 30 days and is the mass of the infarcted tissue divided by the mass of the left ventricle times 100%.
Time frame: 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Myocardial Infarct Size at 30 Days | 17 percentage of total cardiac tissue mass | Standard Deviation 14 |
| Nesiritide | Myocardial Infarct Size at 30 Days | 12 percentage of total cardiac tissue mass | Standard Deviation 9 |
p-value: 0.26t-test, 2 sided