E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 |
The secondary objectives of the trial are to assess the impact of NO inhalation on: 1. MI size at 48-72 h (MRI). 2. MI size normalized to area at risk at 48-72 h (MRI). 3. Myocardial perfusion after PCI. 4. MI transmurality at 48-72 h and 4 months. 5. Myocardial perfusion at 48-72 and 4 months (MRI). 6. Global & regional left ventricular (LV) function and LV mass at 48-72 h and 4 months after MI. MI size as a fraction of LV size at 4 months after MI. 7. Resolution of ST segment elevation at 4 h compared to enrollment. 8. Troponin T levels & CPK-MB area under the curve at 48 h. 9. Change between 48-72 and 4 months in LV end-diastolic volume; end-systolic volume; end-diastolic myocardial wall thickness in infarct, peri-infarct & remote areas; & sphericity index at end-diastole & end-systole. 10. Death; nonfatal recruuent MI; recurrent ischemia necessitating re-hospitalization, PCI, or surgical revascularization; & stroke at 4 months. 11. Safety-determined by reported AEs.
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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 clinical 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 flow (residual stenosis less than 30% if stented and less than 50% if opened by balloon angioplasty).
4.Greater than 18 years of age.
5.Signed IRB 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.Heart block that is expected to require a temporary pacemaker for greater than 72 hours. 6.Prior use of thrombolytic therapy for the current event. 7.Unable to tolerate magnetic resonance imaging (including disallowed metallic implants or BMI >35) or unable to tolerate gadolinium contrast media, including patients with a calculated creatinine clearance less than 60ml/min/ 1.73m2 BSA. 8.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. 9.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. 10.Known or suspected aortic dissection. 11.Prior history of pulmonary disease requiring chronic oxygen therapy. 12.Pregnancy, lactating and women of childbearing potential. 13.Medical problem likely to preclude completion of the study. 14.Use of investigational drugs or device within the 30 days prior to enrollment to the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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 | 3 |
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 | 3 |
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 |