E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Myocardial infarction related cardiogenic shock | |
E.1.1.1 | Medical condition in easily understood language | Cardiogenic shock after myocardial infarction | |
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 | To investigate whether outcomes for patients with cardiogenic shock is better (in terms of survival and renal functioning) when less norepinephrine is administered. | |
E.2.2 | Secondary objectives of the trial | To evaluate cost-effectiveness. | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | 1. Acute myocardial infarction, STEMI or NSTEMI 2. Early revascularization by PCI 3. Cardiogenic shock, characterized by: I. Signs of impaired organ perfusion with at least one of the following criteria: a. Altered mental status b. Cold, clammy skin and extremities c. Oliguria with urine output < 30ml/hour d. Serum lactate > 2.0 mmol/L II. a. Systolic blood pressure (SBP) < 90 mmHg for > 30 minutes, OR b. Use of drugs to maintain SBP > 90 mmHg at presentation before randomization. III. Clinical signs of pulmonary congestion | |
E.4 | Principal exclusion criteria | -Resuscitation > 30 minutes - Mechanical cause of cardiogenic shock (e.g. papillary muscle rupture, ventricular septal rupture) - Onset of shock > 12 hours - Imminent need for mechanical circulatory support -Women < 45 years | |
E.5 End points |
E.5.1 | Primary end point(s) | The composite of all-cause mortality and severe renal failure requiring renal replacement therapy within 30 days after randomization. | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | 30 days after randomization | |
E.5.2 | Secondary end point(s) | All-cause mortality at 30 days Days alive and out of hospital (30 days) Days alive and out of ICU (30 days) Cardiovascular death at 1 year Enzymatic infarct size Lactate clearance (mean + area under the curve 0-36 hours) Days alive and free of mechanical ventilation (30 days) Days alive and free of mechanical circulatory support (30 days) Severe renal failure requiring renal replacement therapy (at 30 days, 1 year) Renal function (during hospital stay and 1 year) Time to peak creatinine (hospital stay) Time to renal replacement therapy Days alive and free of catecholamine therapy (30 days) Vasoactive inotropic score (VIS) (during hospital stay) Time to hemodynamic stabilization (hospital stay) Blood pressure and heart rate during the first 24 hours Hemodynamic parameters (during ICU / CCU admission) Arrhythmias during hospital admission Major vascular complication during hospital admission Infection / sepsis during hospital admission Myocardial re-infarction within 30 days Left ventricular ejection fraction (at day 3, before hospital discharge, and at 1 year) Neurological outcome (at 30 days and 1 year) Protocol adherence / use of bail-out therapy Hospital readmission for cardiac reason within 1 year | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | |
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 | No |
E.6.5 | Efficacy | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description | Lower dose of norepinehprine | |
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 | 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 | 11 |
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 | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |