Please select the eligibility criteria that correspond to the clinical trial below.
Title: Systematic Early Use of Neuromuscular Blocking Agents in ARDS Patients
Brief Summary: The use of neuromuscular blocking agents (NMBA) in ARDS patients has not been extensively investigated. The aim of the study is to show a reduction of the mortality rate of ARDS patients.


Options:
A: Inclusion Criteria:

1. ARDS diagnosed using Berlin definition
2. Eligible patients were at least 18 years of age had acute onset of ARDS.
3. Bilateral opacities in chest radiography
4. No cardiac failure
5. PaO2/FiO2 ratio \< 200

Exclusion Criteria:

1. 72 hours after all inclusion criteria met
2. Pre-existing severe diseases of any major organs
3. Pregnancy
4. Pulmonary hypertension
5. Malignant diseases
6. HIV infections.
B: 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)
C: Inclusion Criteria:

* ARDS with a PaO2 / FiO2 \< 150 with a PEEP \> 5 since less than 48 hrs
* informed consent

Exclusion Criteria:

* NMBA allergy
* Continuous administration of NMBA for ARDS prior inclusion
* Age \< 18 yrs
* SAPS II \> 70
* Persistent air leak
D: Inclusion Criteria:

* Male or female, 18 - 80 years of age (inclusive)
* Diagnosis of ALI with acute onset of PaO2/FiO2 ratio less than or equal to 300, and bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph. The infiltrates may be patchy, diffuse, homogeneous, or asymmetric, and requirement for positive pressure ventilation via an endotracheal tube, and no clinical evidence of left atrial hypertension
* Cause of ALI thought to be associated with infection, sepsis, pneumonia, aspiration, or similar as judged by the PI and/or medical monitor
* The subject must be randomized into the study within 48 hours from the time of diagnosis of ALI
* Period of hemodynamic stability (e.g. 4-6 hours) prior to the initiation of study treatment not requiring resuscitative measures with stable pressor requirements. In this study low-dose arginine vasopressin is not considered a pressor, and is permitted in Parts A and B.
* If mechanically ventilated, duration of mechanical ventilation must be less than 72 hours before dosing begins
* BMI within the range 19.0 - 38.0 kg/m2 inclusive
* The subject or legal decision maker is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
* QTcB or QTcF less than 450 msec; or QTc less than 480 msec in subjects with Bundle Branch Block.
* Alanine aminotransferase (ALT) less than 5 x Upper Limit of Normal (ULN); bilirubin less than or equal to 1.5 x ULN.

Exclusion Criteria:

* Subjects whose clinical condition is deteriorating rapidly or any subject for whom the investigator does not consider there is a reasonable expectation that they will be able to complete the study.
* Known positive Hepatitis B surface antigen, Hepatitis C antibody or HIV antibody
* Current or chronic history of liver disease (Child Pugh score of greater than or equal to 10), or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* Known history of substance abuse or alcohol abuse, within 6 months of the study causing chronic liver disease such as cirrhosis, chronic ascites or portal hypertension, or known evidence of withdrawal syndrome within the past 6 months.
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Inability to discontinue use of Angiotensin converting enzyme type 1 inhibitors or Angiotensin receptor blockers.
* Patients requiring high doses of loop diuretics with significant intravascular volume depletion, as assessed clinically
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation
* Pregnant females as determined by positive serum or urine hCG test prior to dosing
* Lactating females
* Unwillingness or inability to follow the procedures outlined in the protocol
* Subject is legally incapacitated (e.g. a prisoner)
* History of sensitivity to heparin or heparin-induced thrombocytopenia
* Unstable Hemoglobin (Hb less than 7) at time of drug infusion
* Malignancy or other irreversible condition for which 6 month mortality is estimated to be greater than 50%
* Arterial blood pH less than 7.1 or serum HCO3 - less than 15 (if ABG not available) before infusion is started
* Known severe chronic respiratory disease:
* known Forced Expiratory Volume in 1 second (FEV1)/ Forced Vital Capacity (FVC) less than 45% predicted, or
* known chronic hypercapnia (PaCO2 greater than 45 mmHg) or chronic hypoxemia (PaO2 less than 55 mmHg) on FiO2 =0.21, or
* known FEV1 less than 15 ml/kg (e.g. 1L for 70 kg person), or
* known radiographic evidence of chronic interstitial infiltration, or
* known hospitalization within the past six months for respiratory failure (PaCO2 greater than 50 mmHg or PaO2 less than 55 mmHg, or oxygen saturation less than 88% on FiO2 = 0.21), or
* known chronic restrictive, obstructive, neuromuscular, chest wall, or pulmonary vascular disease resulting in severe exercise restriction
* Known history of neuromuscular disease that would affect time on mechanical ventilation or impairs ability to ventilate spontaneously
* Vasculitis with diffuse alveolar hemorrhage
* Lung transplantation
* Pre-existing renal failure on hemodialysis or peritoneal dialysis requiring renal replacement therapy
* A patient will be excluded if in the judgement of the Principle Investigator or GSK medical monitor their participation could jeopardize the health of the subject or the integrity of the study.

Answer: C