Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Comparative, Randomised Controlled Trial for Evaluating the Efficacy of Dexamethasone in the Treatment of Patients With Acute Respiratory Distress Syndrome
Brief Summary: BACKGROUND: Currently, there is no proven pharmacologic treatment for patients with the acute respiratory distress syndrome (ARDS). Great interest remains in the use of corticosteroids for the salvage of patients with severe acute lung injury in the early phase of their disease process, a situation that that has not been evaluated in most published trials. Dexamethasone has never been evaluated in ARDS in a randomized controlled fashion.

HYPOTHESIS AND OBJECTIVES: The investigators hypothesize that adjunctive treatment with intravenous dexamethasone of patients with established ARDS might change the pulmonary and systemic inflammatory response and thereby will increase the number of ventilator-free days and will decrease the extremely high overall mortality. Our goal is to examine the effects of dexamethasone on length of duration of mechanical ventilation (assessed by number of ventilator-free days) and on mortality, in patients admitted into a network of Spanish intensive care units (ICUs) who still meet ARDS criteria at 24 hours after ARDS onset.


Options:
A: Inclusion Criteria:

* 1. Systemic inflammatory response syndrome (SIRS) defined as meeting at least criteria (a) or (b)for a systemic inflammatory response:

  1. White blood cell count \>12,000 or \<4,000 or \>10% band forms
  2. Body temperature \>38 degrees Celsius (C) (any route) or \<36 degrees C (accepting core temperatures only; indwelling catheter, esophageal, rectal)
  3. Heart rate (\> 90 beats/min) or receiving medications that slow heart rate or paced rhythm 2. Suspected or proven infection: Sites of infection include thorax, urinary tract, abdomen, skin, sinuses, central venous catheters, and bacterial meningitis (Appendix A).

     3. ALI as defined by acute onset of:

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  1. PaO2 / FiO2 ≤ 300 (intubated). If altitude \> 1000m, then PaO2 / FiO2 ≤ 300 x (PB/760), and
  2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph, and
  3. Requirement for positive pressure ventilation via an endotracheal tube, and
  4. No clinical evidence of left atrial hypertension, or if measured, a Pulmonary Arterial Wedge Pressure (PAOP) less than or equal to 18 mm Hg. If a patient has a PAOP \> 18 mmHg, then the other criteria must persist for more than 12 hours after the PAOP has declined to ≤ 18 mmHg, and still be within the 48-hour enrollment window.

"Acute onset" is defined as follows: the duration of the hypoxemia criterion (#1) and the chest radiograph criterion (#2) must be ≤ 28 days at the time of randomization. Opacities considered "consistent with pulmonary edema" include any patchy or diffuse opacities not fully explained by mass, atelectasis, or effusion or opacities known to be chronic (\> 28 days). The findings of vascular redistribution, indistinct vessels, and indistinct cardiac borders are not considered "consistent with pulmonary edema".

All ALI criteria (3a-d above) must occur within the same 24 hour period. The onset of ALI is when the last ALI criterion is met. Patients must be enrolled within 48 hours of ALI onset and no more than 7 days from the initiation of mechanical ventilation. SIRS criteria must occur within the 72 hours before or the 24 hours after ALI onset. Information for determining when these time window criteria were met may come from either the Network hospital or a referring hospital reports.

Exclusion Criteria:

1. No consent/inability to obtain consent
2. Age less than 18 years
3. More than 7 days since initiation of mechanical ventilation
4. More than 48 hours since meeting ALI inclusion criteria
5. Patient, surrogate, or physician not committed to full support ).
6. Unable to receive or unlikely to absorb enteral study drug
7. Rosuvastatin specific exclusions

   * Receiving a statin medication within 48 hours of randomization
   * Allergy or intolerance to statins
   * Physician insistence for the use or avoidance of statins during the current hospitalization
   * Creatine Kinase (CK) , alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 times the upper limit of normal
   * Diagnosis of hypothyroidism and not on thyroid replacement therapy
   * Pregnancy or breast feeding
   * Receiving niacin, fenofibrate or cyclosporine, gemfibrozil, atazanavir, lopinavir, ritonavir, daptomycin
8. Severe chronic liver disease
9. Moribund patient not expected to survive 24 hours
10. Chronic respiratory failure defined as PaCO2 \> 60 mm Hg in the outpatient setting
11. Home mechanical ventilation (noninvasive ventilation or via tracheotomy) except for CPAP/BIPAP (Continuous Positive Airway Pressure/BiLevel Positive Airway Pressure) used solely for sleep-disordered breathing
12. Diffuse alveolar hemorrhage from vasculitis
13. Burns \> 40% total body surface
14. Interstitial lung disease of severity sufficient to require continuous home oxygen therapy
15. Unwillingness or inability to utilize the ARDS network 6 ml/kg Predicted Body Weight (PBW) ventilation protocol
16. Cardiac disease classified as NYHA (New York Heart Association) class IV
17. Myocardial infarction within past 6 months
18. Intraparenchymal Central Nervous System (CNS) bleed within a month of randomization.
19. Temperature \>40.3 C in the 6 hours before randomization
B: Inclusion Criteria:

* Age ≥18 years old
* Patients must have acute onset of ARDS, as defined by the American-European Consensus Conference (AECC) criteria for ARDS: (i) having an initiating clinical condition (pneumonia, aspiration, inhalation injury, sepsis, trauma, acute pancreatitis, etc.; (ii) bilateral infiltrates on frontal chest radiograph; (iii) absence of left atrial hypertension, a pulmonary capillary wedge pressure (PCWP) less than 18 mm Hg, or no clinical signs of left heart failure; (iv) severe hypoxemia (a PaO2/FIO2 \<200 mm Hg, regardless of FIO2 or positive end-expiratory pressure (PEEP)
* Be intubated and mechanically ventilated
* Have provided signed written informed consent from the patient or the patient's personal legal representative

Exclusion Criteria:

* Be a woman known to be pregnant or lactating
* Take part in another experimental treatment protocol (simultaneously)
* Brain death
* Terminal-stage cancer or other terminal disease
* Having do-not-resuscitate orders
* Being immune-compromised
* Receiving corticosteroids or immunosuppressive drugs
* Patients in whom more than 24 hours had elapsed after initially meeting the AECC ARDS criteria before consent and results of initial standard ventilator settings could be obtained.
* Have severe chronic obstructive pulmonary disease (COPD)
* Have congestive heart failure
C: Inclusion Criteria:

* age ≥ 18
* intubated and mechanically ventilated male and female patients of the Intensive Care Units of the Department of Anesthesia, General Intensive Care and Pain Control
* meets the criteria of ALI (as defined by the American-European Consensus Conference on ALI/ ARDS):
* Onset of ALI within 48 hours
* Bilateral infiltrates seen on frontal chest radiograph
* PCWP ≤ 18 mm Hg or no clinical evidence of left atrial hypertension
* paO2/ FiO2 ratio ≤ 300 mm Hg
* EVLW in PiCCO® at screening ≥ 8 ml/PBW
* Meeting criteria for extensive hemodynamic monitoring according to investigators discretion
* ICU Patients being mechanically ventilated and are stable in this condition for at least 8 hours
* Negative pregnancy test and adequate contraception in female patients of childbearing potential
* Informed consent:
* For patients that are temporarily unable to consent (e.g. comatose patients) a subsequent informed consent has to be provided.

Exclusion Criteria:

* History of clinically relevant allergies or idiosyncrasies to AP301 or any other inactive ingredient(s) of the investigational product
* Brainstem death at screening
* Current evidence of septic shock as defined by the Surviving Sepsis Campaign (Presence of acute organ dysfunction secondary to infection plus hypotension with systolic blood pressure \< 90 mm Hg or mean arterial pressure (MAP) \< 70 mm Hg for not less than one hour which cannot be reversed with fluid resuscitation)
* Neutrophil count \<0.3 x 109 L
* Patients under immunosuppression: high dose steroids (\> 80 mg Prednisolone /d; \> 300 mg hydrocortisone / d), cancer treatment (chemotherapy or biological) or therapy with other immunosuppressive agents for organ transplantation within 2 weeks
* BMI \< 18.5 or \> 35
* Cardiogenic pulmonary edema diagnosed by echocardiography or pulmonary artery catheter
* Pregnancy / lactation or intention to fall pregnant during the time course of the study
* Women of childbearing potential as well as men of procreative capacity who are not using adequate contraception
* Participation in other interventional drug trials
D: Inclusion Criteria:

* Must meet the following three criteria within a 24-hour period:

  1. Acute onset of PaO2/FiO2 less than or equal to 300 (adjustments made for altitude where appropriate)
  2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
  3. Requirement for positive pressure ventilation via endotracheal tube
* No clinical evidence of left-sided cardiac failure to account for bilateral pulmonary infiltrates

Exclusion Criteria:

* Greater than 48 hours since all inclusion criteria are met
* Neuromuscular disease that impairs ability to ventilate without assistance, (e.g., cervical spinal cord injury at level C5 or higher spinal cord injury amyotrophic lateral sclerosis, Guillain-Barré syndrome or myasthenia gravis)
* Pregnant or breast-feeding
* Severe chronic respiratory disease (i.e., chronic hypercapnia \[PaCO2 greater than 45 mmHg\], chronic hypoxemia \[PaO2 less than 55 mmHg on FiO2 = 0.21\], hospitalization within the last 6 months for respiratory failure \[PaCO2 greater than 50 mm Hg and/or PaO2 less than 55 mmHg on 0.21 FiO2\], secondary polycythemia, severe pulmonary hypertension \[mean PAP (pulmonary artery pressure) greater than 40 mmHg\], or ventilator dependency)
* Burns over greater than 40% of total body surface area
* Cancer or other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
* Allogeneic bone marrow transplant within the 5 years prior to study entry
* Participant, surrogate, or physician is not committed to full support (Exception: a participant will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
* Severe chronic liver disease (Child-Pugh score of 11-15)
* Diffuse alveolar hemorrhage from vasculitis
* Morbid obesity (greater than 1kg/cm body weight.)
* Unwillingness or inability to utilize the ARDS network 6 ml / kg Predicted Body Weight (PBW) ventilation protocol
* Moribund participant and is not expected to survive 24 hours
* No intent to obtain central venous access for monitoring intravascular pressures
* Contraindication to aerosolized albuterol (see Appendix A.8 of the protocol for more information)
* Daily use (prior to study hospitalization) of inhaled beta agonist, corticosteroid, or oral leukotriene modifier
* Unwillingness of primary physician to discontinue inpatient beta agonist use
* Acute myocardial infarction or acute coronary syndrome within 30 days of study entry
* Severe congestive heart failure (see Appendix A5 of the protocol for more information)
* Participation in other experimental medication trial within 30 days of study entry with the exception of the ARDSNet pharmaconutrient nutrition trial (OMEGA)
* Heart rate greater than 85% of maximal predicted heart rate (MHR85) as calculated by MHR85 = 85% x (220-age)
* Currently receiving high frequency ventilation

Answer: B