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

Study Overview
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Brief Summary
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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.

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

Conditions
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Disseminated Intravascular Coagulation

Intervention / Treatment
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* Drug: Antithrombin alfa (INN name)
* Drug: Control (Standard treatment)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent has been obtained from the patient or his/her legally acceptable representative Severe sepsis Disseminated intravascular coagulation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AT-150<br>Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% | Drug: Antithrombin alfa (INN name)<br> <br> |
| Experimental: AT-250<br>Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% | Drug: Antithrombin alfa (INN name)<br> <br> |
| Active Comparator: Control<br>The best standard treatment for the underlying condition only | Drug: Control (Standard treatment)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at Day 28 |  | Day 28 | 
| Mortality at Day 90 |  | Day 90 | 
| 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. | Baseline to Day 6 | 
| 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 | Baseline to Day 6 | 
| Days Alive and Out of ICU Day 28 | Days alive and out of ICU at day 28 for all patients | Baseline to Day 28 | 
| Days Alive and Out of Hospital Day 28 | Days alive and out of Hospital at day 28 for all patients | Baseline to Day 28 | 
| Days Alive and Free of Inotrope/Vasopressor Support Day 28 | Days alive and free of inotrope/vasopressor at day 28 for all patients | Baseline to Day 28 | 
| Days Alive and Off Ventilator Day 28 | Days alive and free of mechanical ventilation at day 28 for all patients | Baseline to Day 28 | 
| Days Alive and Free of Need for Renal Replacement Therapy Day 28 | Days alive and out of renal replacement therapy at day 28 for all patients | Baseline to Day 28 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DIC associated with severe sepsis