Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2 Study to Evaluate Dose and Duration of Treatment of Drotrecogin Alfa (Activated) Using Serial Measurements of Protein C in Patients With Severe Sepsis and Multiple Organ Dysfunction
Brief Summary: In this trial, patients with severe sepsis and low protein C levels will receive drotrecogin alfa (activated) at the normal, approved dose and time of administration \[24 microgram/kilogram/hour (mcg/kg/hour) for 96 hours\] or will receive the normal, approved dose or higher doses than the approved dose for a longer administration time. After the drug administration is complete, the protein C levels from the patients receiving the normal, approved dose will be compared to protein C levels from patients receiving the normal, approved dose or higher dose for a longer duration to determine if the protein C levels improve faster if given higher dose and/or longer administration time.

Note: The protocol was amended to remove the option of shorter infusion durations.


Options:
A: Inclusion Criteria:

* Must be 18 years or older
* Must have evidence of infection
* Must have systemic inflammatory response syndrome (SIRS)
* Must have vasopressor-dependent septic shock

Exclusion Criteria:

* Have received vasopressor therapy (at any dose) for greater than 24 hours prior to the start of study drug
* Have sepsis-induced organ dysfunction for greater than 36 hours prior to the start of the study drug infusion
* Have single organ dysfunction and recent surgery (within 30 days of study entry)
* Have had surgery performed within the 12-hour period immediately preceding the study drug infusion, or are postoperative with evidence of active bleeding, or have planned or anticipated surgery during the infusion period
* Are not expected to survive 28 days given their preexisting uncorrectable medical condition
B: Inclusion Criteria:

* hospitalized in intensive care unit for less than 7 days
* septic shock for less than 24 hours
* at least one proven site of infection
* at least 2 organ dysfunction as defined by a SOFA score =or\> to 3 for at least 6 consecutive hours
* need for vasopressor (dopamine =or\>15µg/kg/min or epinephrine/norepinephrine at =or\>0,25 µg/kg/min for at least 6 consecutive hours, to maintain systolic arterial pressure at 90 mmHg or more OR mean arterial pressure at 6( mmHg or more
* informed consent

Exclusion Criteria:

* pregnancy or breath feeding
* decision not to resuscitate
* underlying disease with an estimated life expectancy of less than 1 month
* formal indication for corticosteroids
* recent surgery (ie within the past 72 hours) or a surgery at high risk of bleeding
* gastro-intestinal bleeding within the past 6 weeks
* chronic liver disease (Child C)
* recent trauma (ie within the past 72 hours)
* intracranial process
* history of stroke, CNS bleeding or traumatic brain injury within the past 3 months
* platelet counts of less than 30000 per cubic millimeter
* formal indication for curative anticoagulant; prophylactic use of heparin is allowed
* any condition of high risk of bleeding as per patient's primary physicians
* hypersensitivity of activated drotrecogin alpha or any other component of the drug
* no affiliation to a social security

Amendments to eligibility criteria were:

On 27/03/2008: Changes in following exclusion criteria :

* "surgical procedure in the past 7 days" was changed for "surgical procedure within 72 hours, or any surgery associated with high risk of bleeding, or a planned surgery within 24 h".
* "chronic liver disease" was clarified as "chronic liver disease with Child score C".
* "severe thrombopenia" was clarified "as severe thrombopenia (\<30,000/mm3, before transfusion).

On 25/08/2009: The exclusion criteria: surgical procedure within 72 hours, or any surgery associated with high risk of bleeding, or a planned surgery within 24 h" was changed for "surgical procedure within 12 hours, or any surgery associated with high risk of bleeding

On 11/06/2010: the inclusion criteria: admitted to the ICU for \< 7 days was removed; and a new exclusion criteria was added: "patients who had a previous episode of sepsis during the same hospital stay

On 18/04/2012: following the withdrawal of DAA from the market: the following exclusion criteria (only related to DAA) were removed :

1. any surgery in the past 12 hours, or any surgery associated with high risk of bleeding;
2. chronic liver disease with a Child score C;
3. recent trauma;
4. any intracranial mass, or stroke or head injury in the past 3 months;
5. severe thrombocytopenia (\< 30.000 /mm3, before platelet transfusion);
6. formal indication for anticoagulation, or any other condition associated with increased risk of bleeding, as appreciated by the patient's physician.
C: Inclusion Criteria:

* Must be 18 years or older
* Must have a suspected or proven infection
* Must have two or more sepsis-associated organ dysfunctions

Exclusion Criteria:

* Documented multiple organ dysfunction greater than 24 hours prior to start of study drug
* Actual body weight less than 30 kg or more than 135 kg
* Platelet count less than 30,000/mm\^3
* Active internal bleeding or at increased risk of bleeding
* Not expected to survive 28 days given the patient's pre-existing uncorrectable medical condition
D: Inclusion Criteria:

* Suspected or proven acute infection.
* Abnormally high or low core body temperature
* Cardiovascular dysfunction which requires the use of vasoactive drugs (such as, dopamine, dobutamine, epinephrine) and is the result of severe sepsis.
* Respiratory dysfunction which requires the use of mechanical ventilation and is the result of severe sepsis.

Exclusion Criteria:

* Patients at increased risk of bleeding.
* Patients at high risk for an intracranial bleed.
* Patients who have undergone a bone marrow transplant.
* Patients with end-stage renal disease.
* Patients whose family or primary care physician is unwilling to allow transfusion of blood products.

Answer: C