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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AT-150 | Experimental | Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 125-175% |
|
| AT-250 | Experimental | Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275% |
|
| Control | Active Comparator | The best standard treatment for the underlying condition only |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Antithrombin alfa (INN name) | Drug |
| ||
| Control (Standard treatment) |
| 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 |
| 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 |
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Inclusion Criteria:
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| FG001 | 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) |
| FG002 | Control | The best standard treatment for the underlying condition only Control |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| BG001 | AT-250 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | 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. | Posted | Count of Participants | Participants | Day 28 |
|
90 days
In this study Critical events were defined to include major bleedings, thromboembolic complications and deaths and are reported as 'Serious Adverse Events'.
All other adverse events were collected and reported together as 'Other (not including Serious) Adverse Events'.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Disclosure | LEO Pharma A/S | +45 44 94 58 88 | disclosure@leo-pharma.com |
| ID | Term |
|---|---|
| D004211 | Disseminated Intravascular Coagulation |
| ID | Term |
|---|---|
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
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| Drug |
|
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 |
Loading dose followed by maintenance IV infusion for 5 days to maintain antithrombin activity at the target level 225-275%
antithrombin alfa (INN name)
| BG002 | Control | The best standard treatment for the underlying condition only Control |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Height | Mean | Standard Deviation | cm |
|
| OG001 | 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) |
| OG002 | Control | The best standard treatment for the underlying condition only Control |
|
|
| Secondary | Mortality at Day 28 | Posted | Count of Participants | Participants | Day 28 |
|
|
|
| Secondary | Mortality at Day 90 | Posted | Count of Participants | Participants | Day 90 |
|
|
|
| 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. | Participants alive on day 6. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Day 6 |
|
|
|
| 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 | Participants alive on day 6. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Day 6 |
|
|
|
| Secondary | Days Alive and Out of ICU Day 28 | Days alive and out of ICU at day 28 for all patients | Posted | Mean | Standard Deviation | Days | Baseline to Day 28 |
|
|
|
| Secondary | Days Alive and Out of Hospital Day 28 | Days alive and out of Hospital at day 28 for all patients | Posted | Mean | Standard Deviation | Days | Baseline to Day 28 |
|
|
|
| Secondary | Days Alive and Free of Inotrope/Vasopressor Support Day 28 | Days alive and free of inotrope/vasopressor at day 28 for all patients | Posted | Mean | Standard Deviation | Days | Baseline to Day 28 |
|
|
|
| Secondary | Days Alive and Off Ventilator Day 28 | Days alive and free of mechanical ventilation at day 28 for all patients | Posted | Mean | Standard Deviation | Days | Baseline to Day 28 |
|
|
|
| Secondary | 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 | Posted | Mean | Standard Deviation | Days | Baseline to Day 28 |
|
|
|
| Secondary | Change From Baseline to Day 6 in Inflammation Marker IL-6 | Participants alive on day 6 who gave a sample. | Posted | Mean | Standard Deviation | pg/mL | Baseline to Day 6 |
|
|
|
| Secondary | Change From Baseline to Day 6 in Inflammation Marker Procalcitonin | Participants alive on day 6 who gave a sample. | Posted | Mean | Standard Deviation | ng/mL | Baseline to Day 6 |
|
|
|
| 4 |
| 10 |
| 5 |
| 10 |
| 10 |
| 10 |
| EG001 | 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) | 6 | 10 | 8 | 10 | 10 | 10 |
| EG002 | Control | The best standard treatment for the underlying condition only Control | 0 | 5 | 5 | 5 | 5 | 5 |
| Portal vein thrombosis | Hepatobiliary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Shock haemorrhagic | Vascular disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Puncture site haemorrhage | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Tracheal haemorrhage | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Pleural haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Operative haemorrhage | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Haematoma | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Gingival bleeding | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Rectal haemorrhage | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Tooth injury | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Necrosis | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Catheter site discharge | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Catheter site haemorrhage | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Arrhythmia | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Cardiomyopathy | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Cyanosis | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Tachyarrhythmia | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Ventricular bigeminy | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Gastric perforation | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Large intestine perforation | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Peritonitis | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Hyperthermia | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Malaise | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Multi-organ failure | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Oedema | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Systemic inflammatory response syndrome | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Biloma | Hepatobiliary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Cholestasis | Hepatobiliary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Cytolytic hepatitis | Hepatobiliary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Acquired hypogammaglobulinaemia | Immune system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Candidiasis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Endocarditis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Infection | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Myocarditis septic | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Blister | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Eschar | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Blood lactic acid increased | Investigations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Vitamin K decreased | Investigations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Arthritis reactive | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Osteitis | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Cyst | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Lung neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Metastasis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Brain oedema | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Leukoencephalomyelitis | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Loss of consciousness | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Neuromyopathy | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Status epilepticus | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Renal cortical necrosis | Renal and urinary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Renal insufficiency | Renal and urinary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Bronchopleural fistula | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Obstructive airways disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Respiratory gas exchange disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Cholecystectomy | Surgical and medical procedures | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Circulatory collapse | Vascular disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Haemodynamic instability | Vascular disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Catheter site haemorrhage | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Catheter site discharge | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Necrosis | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Puncture site heamorrhage | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Tooth injury | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Shock | Vascular disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
LEO Pharma A/S seeks publication of all clinical trials in peer-reviewed journals regardless of whether the findings are positive or negative, and acknowledges the investigators' right to publish results irrespective of outcome. Investigators are permitted to publish their individual data with the prior review and consent of LEO Pharma A/S
| D019851 | Thrombophilia |