It is the intent of the proposed study to further evaluate the safety and efficacy of Tilarginine Acetate Injection as a novel, mortality reducing therapeutic drug for patients with cardiogenic shock complicating acute myocardial infarction.
Conditions
Interventions
Product Name: Tilarginine Acetate Injection
Product Code: -
Pharmaceutical Form: Injection*
INN or Proposed INN: Tilarginine Acetate
CAS Number: -
Current Sponsor code: -
Other descriptive name: -
Co
Sponsors
Arginox Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Confirmation of Acute MI Patients will be considered to have an acute MI if they meet both of the following criteria (a and b): a. Ischemic symptoms for at least 30 minutes AND b. Electrocardiogram (ECG) changes (at least one of the following): - Two or more contiguous leads with =2 mm ST segment elevation - Evolving Q-waves - Left bundle branch block (LBBB) - =2 mm ST segment depression in at least 2 contiguous leads In non-ST elevation MI (including old LBBB), cardiac serum markers above the upper limit of normal in the local laboratory must be confirmed prior to study entry. 2. Confirmation of Persistent Cardiogenic Shock at Randomization Patients must meet all of the following shock criteria (a, b, c and d) at the time of randomization : a. Peripheral signs of tissue hypoperfusion such as decreased urine output and/or cool extremities AND b. SBP 20 mmHg if obtained no more than 3 hours prior to randomization, or an intravenous fluid challenge. The amount of intravenous infusion that is sufficient to exclude hypovolemic will be determined by the clinical status of the subject. Evidence of a sufficient volume infusion includes an increase in central venous pressure (CVP), or development of pulmonary congestion, or resolution of hypotension and shock, AND d. Left ventricular ejection fraction (LVEF) <40% (measured by left ventriculography or echocardiography). 3. Confirmation of Persistent Cardiogenic Shock Five Minutes Prior to Study Drug Administration Patients must meet all of the following shock criteria (a, b, and c) within 5 minutes of study drug administration: a. Continued signs of tissue hypoperfusion such as decreased urine output and/or cool extremities AND b. SBP <100 mm Hg (measured with IABP paused for 60 seconds unless clinically not feasible) despite vasopressor therapy with dopamine dose at least 7 ug/kg/min, or norepinephrine / epinephrine 0.15 ug/kg/min (alone or in any combination that yields 0.15 ug/kg/min) or phenylephrine 0.7 ug/kg/min; AND c. no intercurrent volume loss since randomization 4. Confirmed Patency of the Infarct Related Artery (<70% stenosis with any TIMI flow grade) Infarct related artery patency must be confirmed by coronary angiography. Patency may be established by spontaneous reperfusion, fibrinolytic therapy and/or PCI. Patients with any TIMI flow or no reflow are eligible. 5. Duration of Cardiogenic Shock and time from patency of the IRA The total duration of cardiogenic shock prior to randomization must be less than 24 hours. Subjects must remain in shock for at least 1 hour after the patency of the IRA is confirmed. Randomization cannot occur sooner than 1 hour after demonstration of IRA patency. Are the trial subjects un
Exclusion criteria
Exclusion criteria: Patients will be excluded from participation in the study if ANY of the following criteria apply at the time of randomization: 1. Suspected or documented infection; or 2. Other causes of shock state (e.g., septic, hypovolemic, hemorrhagic, anaphylactic shock); or 3. Shock secondary to acute severe mitral regurgitation (MR) and/or mitral apparatus rupture; or 4. Other severe underlying valvular heart disease, e.g. aortic stenosis, mitral stenosis or aortic insufficiency; or 5. Cardiogenic shock due to predominant RV failure or severe RV dysfunction of any cause; or 6. Cardiogenic shock secondary to rupture of the ventricular septum or ventricular free wall; or 7. Cardiogenic shock secondary due solely to bradyarrhythmia or tachyarrhythmia; or 8. Aortic dissection; or 9. Serum creatinine > 3.0 mg/dl (>264 µmol/L); or 10. End-stage renal disease requiring dialysis; (including peritoneal dialysis); or 11. Adult respiratory distress syndrome (ARDS); or 12. Brain damage that precludes survival despite normalized cardiovascular status; or 13. Irreversible multi-system failure; for example a persistent pH 20 mm Hg between randomization and initiation of study drug; a reduction of 25% or more in the dose of vasopressors administered). If there are signs of resolving shock, a 1-hour observation period for signs of further improvement should be undertaken. At the end of this hour, if SBP =100 mm Hg on vasopressors, no study drug should be given.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to establish the efficacy of Tilarginine Acetate Injection 1.0 mg/kg IV bolus followed by 1.0 mg/kg/hr 5 hour infusion, compared to placebo in reducing all cause mortality at 30 days post randomization in patients with cardiogenic shock complicating acute myocardial infarction (MI). ;Secondary Objective: Secondary endpoints include the following: - the number of subjects demonstrating a resolution of cardiogenic shock - the duration (in days) of cardiogenic shock compared to placebo ;Primary end point(s): The primary endpoint is all cause mortality at 30 days post study drug infusion. | — |
Countries
Belgium, Czech Republic, Germany, Hungary
Outcome results
None listed