Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III International, Multi-Center, Prospective, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Nitric Oxide Synthase Inhibition With Tilarginine Acetate Injection in Patients With Cardiogenic Shock Complicating Acute Myocardial Infarction, or the TRIUMPH Trial
Brief Summary: Tilarginine Acetate Injection is a new type of drug that temporarily stops the body from making a bodily substance called nitric oxide. The body may produce excess nitric oxide following severe heart damage leading to shock. During a heart attack, and especially after a blocked artery causing the heart attack is reopened, a large amount of nitric oxide is released into the heart muscle and into the blood. Normally small amounts of nitric oxide are good for the heart and blood vessels. However, when released in large amounts, such as during a heart attack, it may be harmful, by adding to the damage of the heart attack and lowering the heart's ability to pump blood to the body. It may cause blood pressure to be lowered and reduce the amount of blood flow to the body's vital organs. This may interfere with the body's organs being able to do their work. If Tilarginine Acetate Injection can stop extra nitric oxide from being made, the performance of the heart and blood flow to the organs may get better, which may result in the improvement of symptoms. The purpose of this study (TRIUMPH) is to investigate the safety and effectiveness of Tilarginine Acetate Injection compared to placebo (an inactive fluid that has no effect on the body but looks exactly like the medication being studied). The study will help determine whether Tilarginine Acetate Injection, by temporarily lowering the amount of nitric oxide released into the vital organs can improve blood pressure and the blood flow to the body's organs.


Options:
A: Inclusion Criteria:

* Acute ST-elevation myocardial infarction subject to acute PCI or non-ST elevation myocardial infarction subject to PCI within 72 hours after start of chest pain and:
* Revascularization by PCI,
* Signs of decreased wall-motion in at least 3 of 16 segments of the left ventricle
* Dyspnoea at rest and one of the following:

pulmonary edema, pulmonary congestion,need for CPAP or ventilator, need for IC diuretics or oliguria.

Subgroup of patients in cardiogenic shock: Systolic BP below 90 after 1 hour of volume therapy.

Exclusion Criteria:

* Age below 20 years
* Heart rate above 120 bpm
* Septic shock
* ARDS
* Creatinine \>450 micromol/l
* Hepatic impairment
* Significant mechanical outlet obstruction
* Allergy against study drug medication
* Anaemia (Hb \<8 g/dl)
* Pregnancy
B: Inclusion Criteria:

* Confirmed myocardial infarction (heart attack)
* Confirmed persistent cardiogenic shock
* Confirmed patency of the infarct related artery (heart attack artery has been opened through the use of a blood clot dissolving drug or a balloon or angioplasty heart procedure)
* Less than 24 hour duration of cardiogenic shock (the time since the heart attack occurred and the artery was opened must be less than 24 hours)

Exclusion Criteria:

* Infection
* Other cause of shock (not heart attack)
* Shock due to heart valve disease
* Severe heart valve disease
* Right sided heart failure
* Shock due to arrhythmia (irregular heart rhythm)
* Severe kidney disease
* Aortic dissection (tear in aorta)
* Adult respiratory distress syndrome (ARDS) (severe lung inflammation)
* Severe brain damage
* Severe irreversible multi-system failure (failure of multiple body organs)
* Major chest or abdominal surgical procedure within 30 days except if prior CABG and reocclusion occurs
* Primary pulmonary hypertension (high blood pressure in the arteries of the lungs)
* Age younger than 18 years
* Requirement for emergency coronary artery bypass grafting (CABG) or infarct-related artery occlusion (heart attack artery completely blocked)
* Ongoing or recent participation in another clinical trial of an investigational drug
* Prior enrollment in this study or rapid resolution of cardiogenic shock before treatment (shock gets better before study starts)
* Positive pregnancy test in women who are of childbearing potential
C: Inclusion Criteria:

* Written, signed and dated informed consent
* Male and female patients over 18 years of age. Females of childbearing potential must have a negative pregnancy test and must refrain from breastfeeding. Women who are postmenopausal \[two years since last menstrual cycle\], surgically sterilised or who have undergone a hysterectomy are considered not to be of childbearing potential
* Hospitalised patients with acutely decompensated heart failure
* Left ventricular ejection fraction less than or equal to 30 % as assessed using echocardiography, radionuclide ventriculography or contrast angiography within 12 months
* Clinical need for intravenous inotropic support as evidenced by insufficient response to intravenous diuretics and/or vasodilators (nitroglycerin, nitroprusside) and at least one of the following at screening:

  * oliguria (mean urine output \< 30 ml/h for at least 6 hours) and not a result of hypovolemia
  * dyspnoea at rest or mechanical ventilation for heart failure
  * haemodynamic impairment in those patients with Swan-Ganz catheter inserted (PCWP ≥ 18 mmHg and/or Cardiac Index ≤ 2.2 l/min/m2)

Exclusion Criteria:

* Severe obstruction of ventricular outflow tracts such as haemodynamically significant uncorrected primary valve disease or hypertrophic cardiomyopathy or impaired ventricular filling such as restrictive cardiomyopathy
* Weight ≥ 160 kg
* Cardiac surgery within 30 days before screening
* Stroke within 3 months before screening
* Systolic blood pressure persistently less than 85 mmHg at screening or at baseline
* Heart rate persistently 130 bpm or greater at screening or at baseline
* Serum potassium less than 3.5 mmol/l at screening
* Administration of any inotropic agent (e.g. dobutamine, milrinone, amrinone, enoximone, epinephrine, norepinephrine) except digitalis or dopamine (with dose of less than or equal than 2 mg/kg/min) during the current hospitalisation
* Hypersensitivity to levosimendan or dobutamine or any of their excipients
* A history of Torsades de Pointes
* Severe renal insufficiency (serum creatinine \> 450 mmol/l \[5.0 mg/dl\]) or on dialysis
* Significant hepatic impairment at discretion of the investigator
* Acute bleeding
* Severe anemia (haemoglobin \< 8 g/dl) at screening
* Septicaemia or septic shock
* Other serious diseases limiting life expectancy considerably (e.g. end-stage cancer)
* Participation in a clinical trial with any experimental treatment within 30 days prior to screening or previous participation in the present study
* Administration of levosimendan within 30 days prior to screening
D: Inclusion Criteria:

Cardiogenic shock complicating acute myocardial (STEMI or NSTEMI) with

* intended revascularization (PCI or CABG)
* Systolic blood pressure \< 90 mmHg \> 30 min or inotropes required to maintain pressure \> 90 mmHg during systole
* Signs of pulmonary congestion
* Signs of impaired organ perfusion with at least one of the following:

  * Altered mental status
  * Cold, clammy skin
  * Urine output \<30 ml/h
  * Serum lactate \>2mmol/l
* Informed consent

Exclusion criteria:

* Resuscitation \> 30 minutes
* Cerebral deficit with fixed dilated pupils
* No intrinsic heart action
* Mechanical infarction complication
* Onset of shock \> 12 h
* Severe peripheral artery disease
* Aortic regurgitation \> II.°
* Age \> 90 years
* shock of other cause
* Other severe concomitant disease
* participation in another trial

Answer: B