E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028596 |
E.1.2 | Term | Myocardial infarction |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective 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. |
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E.2.2 | Secondary objectives of the trial |
1. MI size at 48 – 72 hours.
2. MI size normalized to area at risk at 48 – 72 hours.
3. Myocardial perfusion after PCI.
4. Transmurality of infarct at 48 – 72 hours and 4 months.
5. Myocardial perfusion at 48-72 hours and 4 months.
6. Global and regional LV function and LV mass at 48 – 72hr and 4
months after MI and the change in global LV function and mass between
48-72 hr and 4 months. MI size as a fraction of LV size at 4 months after
MI.
7. Resolution of ST segment elevation at 4 hrs compared compared to
enrollment.
8. Troponin T levels and CPK-MB area under the curve at 48 hrs.
9. Change in adverse remodeling parameters at 4 months (compared
with 48–72 hrs10. Death, nonfatal recurrent MI, recurrent ischemia
necessitating re-hospitalization, PCI, or surgical revascularization, and
stroke at 4 months.
11. Safety determined by reported AEs. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Acute myocardial infarction (defined as an episode of chest pain or
related symptom lasting greater than 2 hours but less than 12 hours and
electrocardiographic evidence of ST elevation (measured as 0.08 seconds after the J point; sum 0.6 mV in leads I, II, III, AVL, AVF, V1-
V6).
2. No evidence of congestive heart failure (no S3 or evidence of
pulmonary edema) and normal oxygen saturation on ≤ 2L oxygen by NC.
3. All patients must undergo successful percutaneous coronary
intervention for TIMI 0 or 1 coronary flow with resulting TIMI 2 or 3
(residual stenosis less than 30% if stented and less than 50% if opened
by balloon angioplasty).
4. Age > 18 years.
5. Signed EC approved informed consent. |
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E.4 | Principal exclusion criteria |
1. Prior myocardial infarction (as determined by patient history and/or
ECG), cardiac surgery, or severe pericardial, congenital, cardiomyopathic
or valvular heart disease.
2. Requirement for urgent cardiac surgery.
3. Previous CABG or PCI.
4. Left bundle branch block.
5. Unable to tolerate magnetic resonance imaging (including disallowed
metallic implants or BMI > 35) or unable to tolerate gadolinium contrast
media, including patients with calculated creatinine clearance less than
60 ml/min/1.73 m2 BSA.
6. 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 to presentation.
7. Known or suspected aortic dissection.
8. Prior history of pulmonary disease requiring chronic oxygen therapy.
9. Pregnancy, lactating and woman of childbearing potential.
10. Use of investigational drugs or device within the 30 days prior to
enrollment to the study. Investigational uses of approved therapies will
be allowed.
11. Medical problem likely to preclude completion of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable for this study will be myocardial infarction
size as a fraction of left ventricular size as measured by contrastenhanced cardiac MRI. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. MI size, extent and transmurality of microvascular obstruction at 48 – 72
hours (MRI).
2. MI size normalized to area at risk at 48 – 72 hours (MRI).
3. Myocardial perfusion at coronary angiography at the completion of
PCI (corrected TIMI frame count and myocardial blush grade).
4. Infarct transmurality (as average percent wall thickness in all
segments showing delayed enhancement) at 48 – 72 hours and 4
months.
5. Myocardial perfusion at 48 – 72 hours and 4 months (MRI).
6. Global and regional left ventricular function and left ventricular mass
at 48 – 72hours and 4 months after MI, and the change in global LV
function and mass between 48 – 72 hours and 4 months. MI size as a fraction of LV size at4 months after MI.
7. Resolution of ST segment elevation (serial ECGs) as indicated by the
decrease in the total ST elevation (in mV) at 4 hours compared with that
observed at enrollment.
8. Troponin T levels and CPK-MB area under the curve at 48 hours.
9. Change in adverse remodeling parameters at 4 months (compared
with 48 – 72 hours): changes in LV end-diastolic volume, end-systolic
volume, end-diastolic myocardial wall thickness in infarct, peri-infarct
and remote areas and in sphericity index at end-diastole and endsystole.
10. Incidence of death; nonfatal recurrent myocardial infarction;
recurrent ischemia necessitating re-hospitalization, PCI, or surgical
revascularization; and stroke (i.e. combined CV endpoint) at 4 months.
Enzyme leak during subsequent scheduled PCI will not be considered
new ischemia/MI.
11. Assess the safety of inhaled NO for this use as determined by
reported adverse events (including bleeding and laboratory changes). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
48-72 hours and at 4 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |