Use of Antithrombin in Cardiac Surgery With Cardiopulmonary Bypass

Study Overview
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Brief Summary
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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.

Official Title
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A Prospective Randomized Pilot Study to Evaluate the Effect of Preoperative Antithrombin Supplementation on Postoperative Levels of Antithrombin in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass

Conditions
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Acquired Antithrombin III Deficiency, Coronary Artery Bypass

Intervention / Treatment
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* Drug: Antithrombin III


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female At least 18 years of age Subject needed elective cardiac surgery with cardiopulmonary bypass except for heart transplantation Subject had a baseline ATIII level of less than 100% and equal to or above 60% Subject signed the informed consent form Subject was willing to comply with all aspects of the protocol, including blood sampling, for the total duration of the study Exclusion Criteria: Documented congenital ATIII deficiency or ATIII levels below 60% Subject had a baseline ATIII level of 100% or higher Subject needed emergency (non-elective) surgery Subject needed heart transplantation History of anaphylactic reaction(s) to blood or blood components Allergies to excipients Subject was pregnant Subject had any medical condition that according to the investigators judgment worsens the surgical outcome above the expected Subject had any medical condition which is likely to interfere with the evaluation of the study treatment and/or the satisfactory conduct of the trial according to the investigators judgment Subject had participated in any another investigational study within the last 30 days previous to the inclusion

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antithrombin III treatment group<br>Preoperative ATIII supplementation administered immediately after anesthesia induction | Drug: Antithrombin III<br>* Single dose of antithrombin III sufficient to achieve a preoperative level of 120%<br>* Other names: ATIII;|
| No Intervention: Control group<br>No preoperative ATIII supplementation administered | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antithrombin, ATIII, acquired deficiency, anticoagulants, cardiopulmonary bypass, surgery, complications, postoperative outcomes