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The purpose of this trial is to study the effects of preoperative antithrombin supplementation in patients undergoing cardiac surgery with cardiopulmonary bypass in order to maintain antithrombin levels in a range greater than 58% of functional activity and, eventually, to decrease negative clinical outcomes during the ICU stay.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Antithrombin III treatment group | Experimental | Preoperative ATIII supplementation administered immediately after anesthesia induction |
|
| Control group | No Intervention | No preoperative ATIII supplementation administered |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Antithrombin III | Drug | Single dose of antithrombin III sufficient to achieve a preoperative level of 120% |
|
| Measure | Description | Time Frame |
|---|---|---|
| Postoperative ATIII Levels at the ICU Admission | Measurement of postoperative ATIII functional activity at ICU admission | ICU admission |
| Percentage of Subjects With ATIII Levels of 58% or Higher at ICU Admission | Percentage of subjects with ATIII levels of 58% functional activity or higher at ICU admission | ICU admission |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Subjects With Postoperative Myocardial Infarction | Percentage of subjects with postoperative myocardial infarction defined through enzymatic criteria plus new Q-waves at the electrocardiogram | During ICU stay (maximum 70 days) |
| Percentage of Subjects With Adverse Neurologic Outcome |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marco Ranucci, MD | IRCCS Policlinico San Donato, Milano | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| IRCCS Policlinico San Donato | Milan | Lombardy | 20097 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23102903 | Derived | Ranucci M, Baryshnikova E, Crapelli GB, Woodward MK, Paez A, Pelissero G. Preoperative antithrombin supplementation in cardiac surgery: a randomized controlled trial. J Thorac Cardiovasc Surg. 2013 May;145(5):1393-9. doi: 10.1016/j.jtcvs.2012.09.061. Epub 2012 Oct 25. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Antithrombin III Treatment Group | Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120% |
| FG001 | Control Group | No preoperative ATIII supplementation administered |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
206 subjects were randomized; six were screen failures. 100 subjects in the Anbinex treatment group and 94 subjects in the control group were included in the Intent-to-treat and Per-protocol populations (6 subjects in the control group were excluded). 199 subject were included in the Safety population (100 Anbinex and 99 control).
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| ID | Title | Description |
|---|---|---|
| BG000 | Antithrombin III Treatment Group | Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120% |
| BG001 | Control Group |
| 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 | Postoperative ATIII Levels at the ICU Admission | Measurement of postoperative ATIII functional activity at ICU admission | Intent-to-treat set and Per-protocol set | Posted | Mean | Standard Deviation | IU | ICU admission |
|
From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days)
206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
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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 | Antithrombin III Treatment Group | Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120% |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (Unspecified) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Ken Woodward, BSc, M.Sc | GrifolsTherapeutics Inc. | +1 919-316-6675 | michael.woodward@grifols.com |
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| ID | Term |
|---|---|
| D000990 | Antithrombin III |
| ID | Term |
|---|---|
| D058833 | Antithrombin Proteins |
| D015843 | Serpins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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Percentage of subjects with adverse neurologic outcome defined as: coma, stroke or psychotic behaviors lasting >12 hours after extubation |
| During ICU stay (maximum 70 days) |
| Percentage of Patients With Thromboembolic Events | Percentage of subjects with thromboembolic events defined as perioperative myocardial infarction, stroke, mesenteric infarction, peripheral thromboembolism and pulmonary embolism | During ICU stay (maximum 70 days) |
| ICU Stay Duration | During ICU stay (maximum 70 days) |
| In-hospital Postoperative Mortality | 70 days after ICU admission (maximum) |
| Heparin Resistance | Percentage of subjects with heparin resistance defined as failure to reach an activated clotting time >450 seconds after a dose of up to 400 IU/kg of heparin, or failure to maintain this activated clotting time value despite heparin supplementations of 100 IU/kg per each dose with an interval of at least 30 minutes between doses | Immediately after anesthesia induction |
| Postoperative Blood Loss in First 12 Hours | Blood loss defined as the amount of blood collected in the cardiotomy reservoir from ICU admission through the following 12 hours | ICU admission through 12 hours post-operative |
| Need for Blood Products | Number of units of packed red blood cells, fresh frozen plasma, and/or platelets needed | During ICU stay (maximum 70 days) |
| Percentage of Subjects Needing Surgical Re-exploration | Percentage of subjects needing surgical re-exploration resulting from bleeding | During ICU stay (maximum 70 days) |
| Percentage of Subjects With Low Cardiac Syndrome | Percentage of subjects with low cardiac syndrome defined as the need for major inotropic support or intra-aortic balloon pump | During ICU stay (maximum 70 days) |
| Percentage of Subjects With Renal Dysfunction | Percentage of subjects with renal dysfunction defined as an increase of serum creatinine levels to >2.0 and twice the baseline level or need for renal replacement therapy | During ICU stay (maximum 70 days) |
| Mechanical Ventilation Duration | During ICU stay (maximum 70 days) |
| Length of Hospital Stay | Length of hospital stay (days) in both groups was defined as the discharge date minus the surgery date plus 1 day, during a maximum of 70 days after ICU admission. | During ICU stay (maximum 70 days) |
No preoperative ATIII supplementation administered |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Primary | Percentage of Subjects With ATIII Levels of 58% or Higher at ICU Admission | Percentage of subjects with ATIII levels of 58% functional activity or higher at ICU admission | Intent-to treat set and Per-protocol set | Posted | Number | percentage of participants | ICU admission |
|
|
|
|
| Secondary | Percentage of Subjects With Postoperative Myocardial Infarction | Percentage of subjects with postoperative myocardial infarction defined through enzymatic criteria plus new Q-waves at the electrocardiogram | Intent-to-treat set | Posted | Number | percentage of participants | During ICU stay (maximum 70 days) |
|
|
|
|
| Secondary | Percentage of Subjects With Adverse Neurologic Outcome | Percentage of subjects with adverse neurologic outcome defined as: coma, stroke or psychotic behaviors lasting >12 hours after extubation | Intent-to-treat set | Posted | Number | percentage of participants | During ICU stay (maximum 70 days) |
|
|
|
|
| Secondary | Percentage of Patients With Thromboembolic Events | Percentage of subjects with thromboembolic events defined as perioperative myocardial infarction, stroke, mesenteric infarction, peripheral thromboembolism and pulmonary embolism | Intent-to-treat set | Posted | Number | percentage of participants | During ICU stay (maximum 70 days) |
|
|
|
|
| Secondary | ICU Stay Duration | Intent-to-treat set. One subject in the control group was missing this data. | Posted | Median | Inter-Quartile Range | days | During ICU stay (maximum 70 days) |
|
|
|
|
| Secondary | In-hospital Postoperative Mortality | Intent-to-treat set. One subject in the control group was missing this data. | Posted | Number | percentage of participants | 70 days after ICU admission (maximum) |
|
|
|
|
| Secondary | Heparin Resistance | Percentage of subjects with heparin resistance defined as failure to reach an activated clotting time >450 seconds after a dose of up to 400 IU/kg of heparin, or failure to maintain this activated clotting time value despite heparin supplementations of 100 IU/kg per each dose with an interval of at least 30 minutes between doses | Intent-to-treat set. One subject in the Antithrombin III treatment group was missing this data. | Posted | Number | percentage of participants | Immediately after anesthesia induction |
|
|
|
|
| Secondary | Postoperative Blood Loss in First 12 Hours | Blood loss defined as the amount of blood collected in the cardiotomy reservoir from ICU admission through the following 12 hours | Intent-to-treat set. One subject in the Antithrombin III treatment group was missing this data. | Posted | Least Squares Mean | Standard Error | mL | ICU admission through 12 hours post-operative |
|
|
|
|
| Secondary | Need for Blood Products | Number of units of packed red blood cells, fresh frozen plasma, and/or platelets needed | Intent-to-treat set | Posted | Least Squares Mean | Standard Error | Units | During ICU stay (maximum 70 days) |
|
|
|
|
| Secondary | Percentage of Subjects Needing Surgical Re-exploration | Percentage of subjects needing surgical re-exploration resulting from bleeding | Intent-to-treat set. Two subjects in the Antithrombin III treatment group and 2 subjects in the Control group were missing this data. | Posted | Number | percentage of participants | During ICU stay (maximum 70 days) |
|
|
|
|
| Secondary | Percentage of Subjects With Low Cardiac Syndrome | Percentage of subjects with low cardiac syndrome defined as the need for major inotropic support or intra-aortic balloon pump | Intent-to-treat set. Three subjects in the Antithrombin III treatment group and 1 subject in the Control group were missing this data. | Posted | Number | percentage of participants | During ICU stay (maximum 70 days) |
|
|
|
|
| Secondary | Percentage of Subjects With Renal Dysfunction | Percentage of subjects with renal dysfunction defined as an increase of serum creatinine levels to >2.0 and twice the baseline level or need for renal replacement therapy | Intent-to-treat set | Posted | Number | Percentage of participants | During ICU stay (maximum 70 days) |
|
|
|
|
| Secondary | Mechanical Ventilation Duration | Intent-to-treat set | Posted | Median | Inter-Quartile Range | Days | During ICU stay (maximum 70 days) |
|
|
|
|
| Secondary | Length of Hospital Stay | Length of hospital stay (days) in both groups was defined as the discharge date minus the surgery date plus 1 day, during a maximum of 70 days after ICU admission. | Posted | Median | Inter-Quartile Range | days | During ICU stay (maximum 70 days) |
|
|
|
|
| 32 |
| 100 |
| 96 |
| 100 |
| EG001 | Control Group | No preoperative ATII supplementation administered | 29 | 99 | 97 | 99 |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Atrial flutter | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Cardiac arrest | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Cardiac tamponade | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Cardio-respiratory arrest | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Low cardiac output syndrome | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Ventricular fibrillation | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Ventricular hypokinesia | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Device occlusion | General disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Hyperpyrexia | General disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Acinetobacter infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Endocarditis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Klebsiella infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Pseudomonas infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Serratia infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Staphyloccal infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Wound infection Staphyloccal | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Graft thrombosis | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
|
| Post procedural hemorrhage | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
|
| Vasoplegia syndrome | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
|
| Wound secretion | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
|
| Electrocardiogram ST segment elevation | Investigations | MedDRA (Unspecified) | Systematic Assessment |
|
| Enterococcus test positive | Investigations | MedDRA (Unspecified) | Systematic Assessment |
|
| Seroconversion test | Investigations | MedDRA (Unspecified) | Systematic Assessment |
|
| Staphylcoccus test positive | Investigations | MedDRA (Unspecified) | Systematic Assessment |
|
| Muscle necrosis | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Cerebral hematoma | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Cerebral hemorrhage | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Coma | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Psychotic behavior | Psychiatric disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Oliguria | Renal and urinary disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Acute pulmonary edema | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Acute respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Evidence based treatment | Surgical and medical procedures | MedDRA (Unspecified) | Systematic Assessment |
|
| Hospitalization | Surgical and medical procedures | MedDRA (Unspecified) | Systematic Assessment |
|
| Tricuspid valve repair | Surgical and medical procedures | MedDRA (Unspecified) | Systematic Assessment |
|
| Hemodynamic instability | Vascular disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Hemorrhage | Vascular disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Atrioventricular block | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Supraventricular extrasystoles | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Serositis | General disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Electrocardiogram ST segment elevation | Investigations | MedDRA (Unspecified) | Systematic Assessment |
|
| Hematocrit decreased | Investigations | MedDRA (Unspecified) | Systematic Assessment |
|
| Disorientation | Psychiatric disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Oliguria | Renal and urinary disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Dyspnoa | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Increased bronchial secretion | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Subcutaneous emphysema | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Diuretic therapy | Surgical and medical procedures | MedDRA (Unspecified) | Systematic Assessment |
|
| Hemorrhage | Vascular disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
|
Site may publish results from the Study, after providing Sponsor thirty days' notice prior to submitting a manuscript or other materials related to the Study to any outside party. At Sponsor's request, Site will remove any Confidential Information (other than Study results), and Site will upon Sponsor's request, delay publication or presentation for a period of up to one hundred twenty days to allow Sponsor to protect its interests in any Sponsor's Inventions.
| D000510 |
| Alpha-Globulins |
| D012712 | Serum Globulins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D005916 | Globulins |
| D019774 | Blood Coagulation Factor Inhibitors |
| D001685 | Biological Factors |
| 1.000 |
| 2-Sided |
| No |
| Superiority or Other |
| Platelets (Anbinex n=5, Control n=8) |
|
| 0.7453 |
| 2-Sided |
| No |
| Superiority or Other |
| Units of platelets | ANCOVA | 0.2705 | 2-Sided | No | Superiority or Other |
| 0.6218 |
| 2-Sided |
| No |
| Superiority or Other |