Please select the eligibility criteria that correspond to the clinical trial below.
Title: Prospective, Randomized Phase II Clinical Trial of Activated Protein C (Xigris) Versus Placebo for the Treatment of Acute Lung Injury
Brief Summary: The purpose of this study is to test the efficacy of activated Protein C (Xigris) for improving clinical outcomes in individuals with acute lung injury (ALI).


Options:
A: Inclusion Criteria:

Patients will be eligible for inclusion if they meet all of the below criteria. Criteria 1-3 must all be present within a 24-hour time period and at the time of enrollment:

Acute onset (defined below) of:

1. A need for positive pressure ventilation by an endotracheal or tracheal tube with a PaO2/FiO2 ratio \< 200 with at least 8 cm H2O positive end-expiratory airway pressure (PEEP)
2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
3. No clinical evidence of left atrial hypertension for bilateral pulmonary infiltrates.

In addition to meeting inclusion criteria, enrollment must occur within 96-hours of first meeting ARDS criteria per the Berlin definition of ARDS.

Exclusion Criteria:

1. Age less than 18 years
2. Greater than 96 hours since first meeting ARDS criteria per the Berlin definition of ARDS
3. Pregnant or breast-feeding
4. Prisoner
5. Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last 2 years
6. Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
7. Moderate to severe liver failure (Childs-Pugh Score \> 12)
8. Severe chronic respiratory disease with a PaCO2 \> 50 mm Hg or the use of home oxygen
9. Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest).
10. Major trauma in the prior 5 days
11. Lung transplant patient
12. No consent/inability to obtain consent
13. Moribund patient not expected to survive 24 hours
14. WHO Class III or IV pulmonary hypertension
15. Documented deep venous thrombosis or pulmonary embolism within past 3 months
16. No arterial line/no intent to place an arterial line
17. No intent/unwillingness to follow lung protective ventilation strategy or fluid management protocol
18. Currently receiving extracorporeal life support (ECLS) or high-frequency oscillatory ventilation (HFOV)
B: Inclusion Criteria:

* Diagnosed with ARDS or has risk factors for ARDS; individuals will be considered at risk if they are critically ill and have trauma, sepsis, shock, pneumonia, inhalation injury, drug overdose, pancreatitis, or hypertransfusion
* Onset of ARDS must be between 7 and 28 days prior to study entry
* Since ARDS onset, bilateral infiltrates must have persisted and participants must have required continuous mechanical ventilation
C: Inclusion Criteria:

Patients will be eligible for inclusion if they meet all of the below criteria. Criteria 1-3 must all be present within a 24-hour time period and at the time of enrollment:

Acute onset (defined below) of:

1. A need for positive pressure ventilation by an endotracheal or tracheal tube with a PaO2/FiO2 ratio \< 200 with at least 8 cm H2O positive end-expiratory airway pressure (PEEP)
2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
3. No clinical evidence of left atrial hypertension for bilateral pulmonary infiltrates.

Exclusion Criteria:

1. Age less than 18 years
2. Greater than 96 hours since first meeting ARDS criteria per the Berlin definition of ARDS
3. Pregnant or breast-feeding
4. Prisoner
5. Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last 2 years
6. Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
7. Moderate to severe liver failure (Childs-Pugh Score \> 12)
8. Severe chronic respiratory disease with a PaCO2 \> 50 mm Hg or the use of home oxygen
9. Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
10. Major trauma in the prior 5 days
11. Lung transplant patient
12. No consent/inability to obtain consent
13. Moribund patient not expected to survive 24 hours
14. World Health Organization (WHO) Class III or IV pulmonary hypertension
15. Documented deep venous thrombosis or pulmonary embolism within past 3 months
16. No arterial line/no intent to place an arterial line
17. No intent/unwillingness to follow lung protective ventilation strategy or fluid management protocol
18. Currently receiving extracorporeal life support (ECLS) or high-frequency oscillatory ventilation (HFOV)
D: Inclusion Criteria:

* PaO2/FiO2 levels less than or equal to 300
* Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
* Positive pressure ventilation through an endotracheal tube or tracheostomy
* No clinical evidence of left atrial hypertension that would explain the pulmonary infiltrates; if measured, pulmonary arterial wedge pressure less than or equal to 18 mm Hg

Exclusion Criteria:

* Family / patient refuses
* Patient / surrogate unavailable
* Attending refuses
* Age younger than 18 years
* Severe sepsis and Acute Physiology and Chronic Health Evaluation (APACHE) II scores greater than 25 within 48 hours of onset of severe sepsis
* Greater than 72 hours since all inclusion criteria are met
* Neuromuscular disease that impairs ability to ventilate without assistance, such as C5 or higher spinal cord injury, amyotrophic lateral sclerosis, Guillain-Barré syndrome, myasthenia gravis, or kyphoscoliosis
* Pregnant
* Severe chronic respiratory disease
* Weighs more than 160 kg
* Burns to more than 70% of total body surface area
* Cancer or other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
* Bone marrow transplant in the 5 years prior to study entry
* Not committed to full support
* Severe chronic liver disease, as determined by a Child-Pugh Score of 11 to 15
* Diffuse alveolar hemorrhage from vasculitis
* Participation in another experimental medication study within 30 days of study entry
* Patients who have already received APC therapy
* Active internal bleeding
* Hemorrhagic or ischemic stroke within 3 months of study entry
* Intracranial or intraspinal surgery or severe head trauma within 2 months of study entry
* Trauma with an increased risk of life-threatening bleeding
* Presence of an epidural catheter
* Intracranial neoplasm mass lesion or evidence of cerebral herniation
* High risk of intracranial hemorrhage, as determined by 1 of the following: 1) intracranial or spinal pathology which places individuals at risk for intracranial hemorrhage (e.g., arterio-venous malformation or previous intracranial bleeding events, not including meningitis); 2) acute change in neurological status with focal neurological findings; 3) documented intracranial hypertension by lumbar puncture or imaging; or 4) seizures in which there is a clinical suspicion of intracranial hemorrhage
* Known bleeding diathesis
* Concurrent therapeutic heparin (greater than 14 units/kg/hr)
* Platelet count less than 30,000 x 106/L, even if the platelet count is increased after transfusions
* Prothrombin time greater than 3.0 INR
* Gastrointestinal bleeding within 6 weeks of study entry
* Concurrent need for systemic anticoagulation with therapeutic unfractionated heparin or low molecular weight heparin during the study drug infusion
* Concurrent administration of an anticoagulant (other than subcutaneous heparin for prophylaxis)
* Concurrent need for platelet glycoprotein Iib/IIIa antagonists or any other antiplatelet agents (patients taking aspirin or other antiplatelet agents at study entry are eligible if medication can be discontinued during study drug infusion)
* Surgery within 30 days of study entry and single organ failure

Answer: D