Evaluate Protein C Levels in Severe Sepsis Patients on Dr... | NCT00386425

ID	Type	Description	Link
F1K-MC-EVDK	Other Identifier	Eli Lilly and Company

Label	Type	Description	Intervention Names
Standard therapy	Experimental	24 microgram/kilogram/hour (mcg/kg/hr) for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours	Drug: Drotrecogin alfa (activated)
Alternative therapy:moderate protein C deficiency	Experimental	24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 48 to 144 hours (original protocol) or an additional 72 to 144 hours (amended protocol)	Drug: Drotrecogin alfa (activated)
Alternative therapy:severe protein C deficiency	Experimental	24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for 48 to 144 hours (original protocol) or an additional 72 to 144 hours (amended protocol)	Drug: Drotrecogin alfa (activated)

Name	Type	Description	Arm Group Labels	Other Names
Drotrecogin alfa (activated)	Drug	intravenous	Alternative therapy:moderate protein C deficiency Alternative therapy:severe protein C deficiency Standard therapy

Measure	Description	Time Frame
Mean Change in Protein C Levels From Day 1 to Day 7	Mean change in protein C from Study Day 1 to Study Day 7 was tested using an unadjusted two-sample t-test with a two-sided alpha of 0.05. To be included in the primary analysis, Intention-to-Treat (ITT) patients must have at least 1 protein C value available at 24 hours or earlier and at least 1 protein C value at a post-24-hour timepoint.	Day 1, Day 7

Measure	Description	Time Frame
Mean Change in Protein C Level From Study Day 1 to Study Day 7 in Patients With Moderate and Severe Protein C Deficiency	Moderate Protein C Deficiency: A protein C level greater than half the lower limit of normal. Severe Protein C Deficiency: A protein C level less than or equal to half the lower limit of normal.	Day 1, Day 7

Measure	Description	Time Frame
Mortality for Severe Protein C Deficiency	Twenty-eight day mortality is the patient's mortality status at the predefined timepoint of 672 hours from the start of study drug infusion. Hospital mortality is the patient's survival status at the end of the hospital stay or study day 90 (if the patient remains in the hospital).	28 Days, up to 90 days

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.		Phoenix	Arizona	85013

PubMed Identifier	Type	Citation	Retractions
21176144	Derived	Shorr AF, Janes JM, Artigas A, Tenhunen J, Wyncoll DL, Mercier E, Francois B, Vincent JL, Vangerow B, Heiselman D, Leishman AG, Zhu YE, Reinhart K; RESPOND investigators. Randomized trial evaluating serial protein C levels in severe sepsis patients treated with variable doses of drotrecogin alfa (activated). Crit Care. 2010;14(6):R229. doi: 10.1186/cc9382. Epub 2010 Dec 21.

ID	Title	Description
FG000	Standard Therapy	24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours
FG001	Alternative Therapy	Moderate Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 to 144 hours Severe Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for an additional 72 to 144 hours

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00062.31± 16.11 BG00161.91± 14.44 BG00266.63± 12.82 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00090 BG00176 BG002

Race/Ethnicity, Customized

Number

Participants

Title

Denominators

Categories

African

Title	Measurements
	BG00013 BG0014 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Australia

Title	Measurements
	BG0002 BG0011 BG002

Recent Surgery

Recent surgery was defined as an intervention performed under general or regional anesthesia that had some relationship to the present sepsis episode within 30 days of study entry.

Number

participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG00068 BG00161

Number of organ dysfunctions

Cardiovascular: systolic blood pressure (SBP) ≤90 mmHg or mean arterial pressure (MAP) ≤70 mmHg for >1 hour despite fluid resuscitation (FR), adequate intravascular volume, or vasopressors to maintain SBP ≥90 mmHg or MAP≥70 mmHg; Renal: average output <0.5 mL/kg/hr for 1 hr despite FR; Respiratory: Pressure of Arterial Oxygen (O2) to Fractional Inspired O2 (PaO2/FiO2) ≤250; Hematology: platelet count <80,000/mm^3 or 50% decrease in count from highest over 3 days prior to study; Unexplained acidosis: pH≤7.3 or base deficit ≥5.0 mEq/L AND plasma lactate level >1.5 times upper limit of normal.

Mean

Standard Deviation

organ dysfunctions

Title

Denominators

Categories

Title	Measurements
	BG0003.08± 0.86 BG001

Time of onset of Second organ dysfunction to start of drug infusion

Mean time between the onset of a second organ dysfunction (cardiovascular, renal, respiratory, hematology, and unexplained metabolic acidosis) to the start of study drug infusion.

Mean

Standard Deviation

hours

Title

Denominators

Categories

Title	Measurements
	BG00015.3± 7.0 BG001

Total Sequential Organ Failure Assessment (SOFA) score

The presence of 5 organ dysfunctions (cardiovascular, respiratory, renal, hepatic, coagulation) was assessed using a Sequential Organ Failure Assessment (SOFA) score. Each organ has a possible dysfunction score of 0 to 4, for a total SOFA score range of 0 (no organ dysfunction) to 20 (all organs with dysfunction).

Mean

Standard Deviation

units on a scale

Title

Denominators

Categories

Title	Measurements
	BG0008.38± 2.83 BG001

Acute Physiology And Chronic Health Evaluation (APACHE) II Score

Acute Physiology and Chronic Health Evaluation II. A classification system that assessed a patient's severity of disease based on 12 physiologic measurements, age, and previous health status. Total scores range from 0 to 71. A higher score indicates increasing severity of disease and a greater likelihood of mortality.

Mean

Standard Deviation

units on a scale

Title

Denominators

Categories

Title	Measurements
	BG00026.34± 7.70 BG001

Use of vasopressor

Number

participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG000190 BG001183 BG002

Mechanical ventilation

Number

participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG000178 BG001158 BG002

Protein C level

Mean

Standard Deviation

Percent Protein C Activity

Title

Denominators

Categories

Title	Measurements
	BG00044± 19 BG00141± 20 BG002

Central laboratory protein C class

Moderate Protein C Deficiency: A protein C level greater than half the lower limit of normal.

Severe Protein C Deficiency: A protein C level less than or equal to half the lower limit of normal.

Number

participants

Title

Denominators

Categories

Severe deficiency

Title	Measurements
	BG00097 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Mean Change in Protein C Levels From Day 1 to Day 7

Mean change in protein C from Study Day 1 to Study Day 7 was tested using an unadjusted two-sample t-test with a two-sided alpha of 0.05. To be included in the primary analysis, Intention-to-Treat (ITT) patients must have at least 1 protein C value available at 24 hours or earlier and at least 1 protein C value at a post-24-hour timepoint.

Intent to Treat (ITT) Last Observation Carried Forward (LOCF) population.

Posted

Mean

Standard Deviation

Percent Protein C Activity

Day 1, Day 7

ID	Title	Description
OG000	Standard Therapy	24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours
OG001	Alternative Therapy	Moderate Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 to 144 hours Severe Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for an additional 72 to 144 hours

Units	Counts
Participants	OG000227 OG001206

Title

Denominators

Categories

Protein C Day 1, n=226, n=205

Title	Measurements
	OG00055± 24 OG00152± 24

Protein C Day 7, n=221, n=203

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		t-test, 2 sided		0.011	p-value is for change to Day 7						95						No	Superiority or Other

Secondary

Mean Change in Protein C Level From Study Day 1 to Study Day 7 in Patients With Moderate and Severe Protein C Deficiency

Moderate Protein C Deficiency: A protein C level greater than half the lower limit of normal.

Severe Protein C Deficiency: A protein C level less than or equal to half the lower limit of normal.

ITT moderately deficient population, ITT severely deficient population

Posted

Mean

Standard Deviation

Percent Protein C Activity

Day 1, Day 7

ID	Title	Description
OG000	Standard Therapy	24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours
OG001	Alternative Therapy	Moderate Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 to 144 hours Severe Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for an additional 72 to 144 hours

Units	Counts
Participants	OG000

Secondary

Day 28 All-Cause Mortality

ITT population

Posted

Number

percentage of participants

Day 0 through Day 28

ID	Title	Description
OG000	Standard Therapy	24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours
OG001	Alternative Therapy	Moderate Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 to 144 hours Severe Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for an additional 72 to 144 hours

Units	Counts
Participants	OG000

Secondary

Hospital Mortality (up to Day 90)

ITT population

Posted

Number

Percentage of participants

Day 0 to hospital discharge or Day 90

ID	Title	Description
OG000	Standard Therapy	24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours
OG001	Alternative Therapy	Moderate Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 to 144 hours Severe Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for an additional 72 to 144 hours

Units	Counts
Participants	OG000

Secondary

28-Day Time Averaged Sequential Organ Failure (SOFA) Score

ITT population

Posted

Mean

Standard Deviation

Units on a scale

Day 0, Day 28

ID	Title	Description
OG000	Standard Therapy	24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours
OG001	Alternative Therapy	Moderate Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 to 144 hours Severe Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for an additional 72 to 144 hours

Units	Counts
Participants	OG000

Secondary

Number of Participants With Serious Adverse Events (SAE) and Serious Bleeding Events (SBE) by Time Period

Serious bleeding events (SBE): intracranial hemorrhage, life-threatening or fatal bleed, or bleeding event assessed as an SAE. Patients may have multiple events with onset in different time periods. SAEs include SBEs. The 3 SBEs in Alternative-Moderate Deficiency arm (days 5-8) occurred after completion of study drug infusion. One event (pleural haemorrhage) occurred same day of completion of infusion and 2 events (cerebral haemorrhage, shock haemorrhagic) occurred day after completion.

Randomized participants who received randomized therapy (intention to treat population).

Posted

Number

number of patients with at least 1 event

Day 0 through Day 28

ID	Title	Description
OG000	Standard Therapy - Severe Deficiency	24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours
OG001	Standard Therapy - Moderate Deficiency	24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours
OG002	Alternative Therapy - Severe Deficiency	Severe Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for an additional 72 to 144 hours

Secondary

Mortality by Protein C Normalized Versus Not-normalized

Normalization was defined as having 2 consecutive protein C measurements above the lower limit of normal through Study Day 7.

ITT Population - All patients who are randomly assigned to treatment and receive any amount of randomized therapy

Posted

Number

Percentage of participants

28 days

ID	Title	Description
OG000	Normalized Protein C
OG001	Did Not Normalize Protein C

Units	Counts
Participants	OG000

Other Pre-specified

Mortality for Severe Protein C Deficiency

Twenty-eight day mortality is the patient's mortality status at the predefined timepoint of 672 hours from the start of study drug infusion. Hospital mortality is the patient's survival status at the end of the hospital stay or study day 90 (if the patient remains in the hospital).

ITT Population - All patients who are randomly assigned to treatment and receive any amount of randomized therapy. ITT patients with severe protein C deficiency. Severe deficiency is defined by the 24-hour local laboratory protein C value reported to the Interactive voice response system (IVRS).

Posted

Number

Percentage of participants

28 Days, up to 90 days

ID	Title	Description
OG000	Standard Therapy	24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours
OG001	Alternative Therapy	Moderate Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 to 144 hours Severe Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for an additional 72 to 144 hours

Units	Counts
Participants

Post-Hoc

Mortality for Moderate Protein C Deficiency by Infusion Duration

ITT Population - ITT Switch-No Population, ITT patients who did not answer yes to the switch question.

Posted

Number

percent participants deceased

28 Days

ID	Title	Description
OG000	Standard Therapy	24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours
OG001	Alternative Therapy	Moderate Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 to 144 hours Severe Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for an additional 72 to 144 hours

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Arrhythmia	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0013 events1 affected236 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Cardiac arrest	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0012 events2 affected236 at risk
Cardiac failure	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Electromechanical dissociation	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0002 events1 affected250 at risk EG0010 events0 affected236 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0011 events1 affected236 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Faeces discoloured	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Intestinal ischaemia	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0012 events2 affected236 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Intra-abdominal haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Peritoneal haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Peritonitis	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Catheter site haemorrhage	General disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0012 events2 affected236 at risk
Death	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Hepatic haemorrhage	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Abdominal sepsis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Candida pneumonia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Empyema	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Endocarditis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Endocarditis staphylococcal	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Pneumonia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0011 events1 affected236 at risk
Sepsis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0012 events2 affected236 at risk
Septic shock	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0014 events4 affected236 at risk
Staphylococcal infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Anastomotic complication	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Anastomotic leak	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Gastrointestinal anastomotic leak	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Suture related complication	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Urinary bladder rupture	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Vascular graft complication	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Vascular pseudoaneurysm	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Haemoglobin decreased	Investigations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Platelet count decreased	Investigations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Fistula	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Metastasis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Central nervous system lesion	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Cerebral haematoma	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Hypoxic encephalopathy	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0012 events2 affected236 at risk
Polyneuropathy	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Status epilepticus	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Renal haemorrhage	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Asphyxia	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0011 events1 affected236 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Pleural haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0012 events2 affected236 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0011 events1 affected236 at risk
Pulmonary fistula	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events1 affected250 at risk EG0010 events0 affected236 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Air embolism	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Arterial haemorrhage	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Extremity necrosis	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Haematoma	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Hypotension	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Ischaemia	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Shock	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0012 events2 affected236 at risk
Shock haemorrhagic	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected250 at risk EG0013 events3 affected236 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0005 events5 affected250 at risk EG0011 events1 affected236 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Aphthous stomatitis	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected250 at risk EG0012 events2 affected236 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0012 events1 affected236 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0011 events1 affected236 at risk
Small intestinal haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Bloody discharge	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Catheter site haemorrhage	General disorders	MedDRA 12.0	Systematic Assessment	EG0006 events4 affected250 at risk EG0019 events5 affected236 at risk
Mucosal haemorrhage	General disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0012 events2 affected236 at risk
Puncture site haemorrhage	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Vessel puncture site haemorrhage	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Abdominal infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Aspergillosis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Bacteraemia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Candidiasis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0012 events2 affected236 at risk
Catheter sepsis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0011 events1 affected236 at risk
Citrobacter infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Clostridial infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Empyema	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Enterobacter infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Enterobacter pneumonia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Enterococcal infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Escherichia urinary tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Fungal infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Gastroenteritis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Genital infection fungal	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Klebsiella infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Lung infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Lung infection pseudomonal	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Morganella infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Oral herpes	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Pneumonia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0012 events2 affected236 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Pseudomembranous colitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Pseudomonas infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected250 at risk EG0012 events2 affected236 at risk
Respiratory tract infection bacterial	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Staphylococcal infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0012 events2 affected236 at risk
Stenotrophomonas infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Systemic candida	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Tracheitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Urinary tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Urinary tract infection bacterial	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Urinary tract infection enterococcal	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Urinary tract infection fungal	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Viral infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Wound infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Wound infection fungal	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Bloody airway discharge	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Operative haemorrhage	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0012 events2 affected236 at risk
Post procedural haematuria	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0011 events1 affected236 at risk
Tracheal haemorrhage	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected250 at risk EG0010 events0 affected236 at risk
Bacteria blood identified	Investigations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Blood urine present	Investigations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Haematocrit decreased	Investigations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Haemoglobin decreased	Investigations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Platelet count decreased	Investigations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Prothrombin time shortened	Investigations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0012 events2 affected236 at risk
Sputum culture positive	Investigations	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Haematuria	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0015 events5 affected236 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected236 at risk
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0011 events1 affected236 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected236 at risk
Haematoma	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected250 at risk EG0011 events1 affected236 at risk
Wound haemorrhage	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0010 events0 affected236 at risk

ID	Term
D007239	Infections
D018746	Systemic Inflammatory Response Syndrome
D007249	Inflammation
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	Standard Therapy	24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours
BG001	Alternative Therapy	Moderate Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 to 144 hours Severe Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for an additional 72 to 144 hours
BG002	Randomized Non-ITT Population
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Standard Therapy	Participants assigned to standard therapy (24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 hours) who received any amount of study drug.			33	250	51	250
EG001	Alternative Therapy	Participants assigned to alternative therapy (Moderate Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 24 mcg/kg/hr for an additional 72 to 144 hours Severe Protein C Deficiency: 24 mcg/kg/hr for 24 hours, followed by 30 or 36 mcg/kg/hr for an additional 72 to 144 hours) who received any amount of study drug.			48	236	46	236