Recombinant Human Antithrombin (ATryn®) in the Treatment of Patients With DIC Associated With Severe Sepsis

Exploratory Efficacy and Safety, Pharmacokinetics and Dose Finding Study of ATryn® (Antithrombin Alfa) in Patients With Disseminated Intravascular Coagulation Associated With Severe Sepsis

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00506519

Enrollment

Registered

2007-07-25

Start date

2007-07-31

Completion date

2009-03-31

Last updated

2025-03-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Disseminated Intravascular Coagulation

Keywords

DIC associated with severe sepsis

Brief summary

The primary objective of the study is to explore the efficacy and safety of ATryn® (antithrombin alfa) for the treatment of disseminated intravascular coagulation (DIC) associated with severe sepsis, when administered by continuous intravenous (IV) infusion over five days.

Interventions

DRUGAntithrombin alfa (INN name)

DRUGControl (Standard treatment)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Signed informed consent has been obtained from the patient or his/her legally acceptable representative * Severe sepsis * Disseminated intravascular coagulation

Design outcomes

Primary

Measure	Time frame	Description
Patients Alive on Day 28, Having Had an Improvement in the DIC Score (Overt or Non-overt) by at Least 2 Points Between Baseline and Day 6 and Having Had no Worsening of the SOFA Score Between Baseline and Day 6.	Day 28	Disseminated Intravascular Coagulation (DIC) ranges from 0 to 8 points, the higher the score the worse coagulation/outcome. Sepsis-related Organ Failure Assessment (SOFA) is a composite score of scores for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 to 4 with a higher score given for worse organ function. The scores are then added together to give a total range from 0 to 24 with a higher score representing a worse outcome.

Secondary

Measure	Time frame	Description
Mortality at Day 90	Day 90	—
Change From Baseline to Day 6 in SOFA Score Among Survivors on Day 6	Baseline to Day 6	Sepsis-related Organ Failure Assessment (SOFA) is a composite score of scores for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 to 4 with a higher score given for worse organ function. The scores are then added together to give a total range from 0 to 24 with a higher score representing a worse outcome.
Change From Baseline to Day 6 in DIC Score Among Survivors on Day 6	Baseline to Day 6	Disseminated Intravascular Coagulation (DIC) ranges from 0 to 8 points, the higher the score the worse coagulation/outcome
Days Alive and Out of ICU Day 28	Baseline to Day 28	Days alive and out of ICU at day 28 for all patients
Days Alive and Out of Hospital Day 28	Baseline to Day 28	Days alive and out of Hospital at day 28 for all patients
Mortality at Day 28	Day 28	—
Days Alive and Off Ventilator Day 28	Baseline to Day 28	Days alive and free of mechanical ventilation at day 28 for all patients
Days Alive and Free of Need for Renal Replacement Therapy Day 28	Baseline to Day 28	Days alive and out of renal replacement therapy at day 28 for all patients
Change From Baseline to Day 6 in Inflammation Marker IL-6	Baseline to Day 6	—
Change From Baseline to Day 6 in Inflammation Marker Procalcitonin	Baseline to Day 6	—
Days Alive and Free of Inotrope/Vasopressor Support Day 28	Baseline to Day 28	Days alive and free of inotrope/vasopressor at day 28 for all patients

Participant flow

Participants by arm

Arm	Count
AT-150 Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% antithrombin alfa (INN name)	10
AT-250 Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% antithrombin alfa (INN name)	10
Control The best standard treatment for the underlying condition only Control	5
Total	25

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	1	0	0
Overall Study	Death	4	6	0

Baseline characteristics

Characteristic	AT-150	AT-250	Control	Total
Age, Continuous	57 years STANDARD_DEVIATION 16.6	65.5 years STANDARD_DEVIATION 19.4	58 years STANDARD_DEVIATION 22.9	60.6 years STANDARD_DEVIATION 18.7
Height	163 cm STANDARD_DEVIATION 4.2	169 cm STANDARD_DEVIATION 14.1	161 cm STANDARD_DEVIATION 13.7	165 cm STANDARD_DEVIATION 11.1
Race/Ethnicity, Customized Ethnic origin Asian	2 Participants	0 Participants	0 Participants	2 Participants
Race/Ethnicity, Customized Ethnic origin Caucasian	8 Participants	10 Participants	5 Participants	23 Participants
Sex: Female, Male Female	8 Participants	4 Participants	4 Participants	16 Participants
Sex: Female, Male Male	2 Participants	6 Participants	1 Participants	9 Participants
Weight	75.6 kg STANDARD_DEVIATION 11.3	77.1 kg STANDARD_DEVIATION 14.5	71.4 kg STANDARD_DEVIATION 28.2	75.4 kg STANDARD_DEVIATION 16.2

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	4 / 10	6 / 10	0 / 5
other Total, other adverse events	10 / 10	10 / 10	5 / 5
serious Total, serious adverse events	5 / 10	8 / 10	5 / 5

Outcome results

Primary

Patients Alive on Day 28, Having Had an Improvement in the DIC Score (Overt or Non-overt) by at Least 2 Points Between Baseline and Day 6 and Having Had no Worsening of the SOFA Score Between Baseline and Day 6.

Disseminated Intravascular Coagulation (DIC) ranges from 0 to 8 points, the higher the score the worse coagulation/outcome. Sepsis-related Organ Failure Assessment (SOFA) is a composite score of scores for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 to 4 with a higher score given for worse organ function. The scores are then added together to give a total range from 0 to 24 with a higher score representing a worse outcome.

Time frame: Day 28

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
AT-150	Patients Alive on Day 28, Having Had an Improvement in the DIC Score (Overt or Non-overt) by at Least 2 Points Between Baseline and Day 6 and Having Had no Worsening of the SOFA Score Between Baseline and Day 6.	2 Participants
AT-250	Patients Alive on Day 28, Having Had an Improvement in the DIC Score (Overt or Non-overt) by at Least 2 Points Between Baseline and Day 6 and Having Had no Worsening of the SOFA Score Between Baseline and Day 6.	2 Participants
Control	Patients Alive on Day 28, Having Had an Improvement in the DIC Score (Overt or Non-overt) by at Least 2 Points Between Baseline and Day 6 and Having Had no Worsening of the SOFA Score Between Baseline and Day 6.	2 Participants

Secondary

Change From Baseline to Day 6 in DIC Score Among Survivors on Day 6

Disseminated Intravascular Coagulation (DIC) ranges from 0 to 8 points, the higher the score the worse coagulation/outcome

Time frame: Baseline to Day 6

Population: Participants alive on day 6.

Arm	Measure	Value (MEAN)	Dispersion
AT-150	Change From Baseline to Day 6 in DIC Score Among Survivors on Day 6	-3.0 score on a scale	Standard Deviation 1.7
AT-250	Change From Baseline to Day 6 in DIC Score Among Survivors on Day 6	-2.2 score on a scale	Standard Deviation 2.4
Control	Change From Baseline to Day 6 in DIC Score Among Survivors on Day 6	-3.0 score on a scale	Standard Deviation 1.6

Secondary

Change From Baseline to Day 6 in Inflammation Marker IL-6

Time frame: Baseline to Day 6

Population: Participants alive on day 6 who gave a sample.

Arm	Measure	Value (MEAN)	Dispersion
AT-150	Change From Baseline to Day 6 in Inflammation Marker IL-6	-68429 pg/mL	Standard Deviation 192828
AT-250	Change From Baseline to Day 6 in Inflammation Marker IL-6	-13153 pg/mL	Standard Deviation 31801
Control	Change From Baseline to Day 6 in Inflammation Marker IL-6	-69651 pg/mL	Standard Deviation 141889

Secondary

Change From Baseline to Day 6 in Inflammation Marker Procalcitonin

Time frame: Baseline to Day 6

Population: Participants alive on day 6 who gave a sample.

Arm	Measure	Value (MEAN)	Dispersion
AT-150	Change From Baseline to Day 6 in Inflammation Marker Procalcitonin	-203.8 ng/mL	Standard Deviation 340.2
AT-250	Change From Baseline to Day 6 in Inflammation Marker Procalcitonin	-51.1 ng/mL	Standard Deviation 49.6
Control	Change From Baseline to Day 6 in Inflammation Marker Procalcitonin	-139.6 ng/mL	Standard Deviation 146.2

Secondary

Change From Baseline to Day 6 in SOFA Score Among Survivors on Day 6

Sepsis-related Organ Failure Assessment (SOFA) is a composite score of scores for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each system is scored from 0 to 4 with a higher score given for worse organ function. The scores are then added together to give a total range from 0 to 24 with a higher score representing a worse outcome.

Time frame: Baseline to Day 6

Population: Participants alive on day 6.

Arm	Measure	Value (MEAN)	Dispersion
AT-150	Change From Baseline to Day 6 in SOFA Score Among Survivors on Day 6	-0.2 score on a scale	Standard Deviation 1.2
AT-250	Change From Baseline to Day 6 in SOFA Score Among Survivors on Day 6	-0.3 score on a scale	Standard Deviation 1.5
Control	Change From Baseline to Day 6 in SOFA Score Among Survivors on Day 6	0.2 score on a scale	Standard Deviation 1.1

Secondary