Safety and Efficacy of Preoperative Antithrombin Supplementation in Patients Undergoing High-Risk Cardiopulmonary Bypass
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|ClinicalTrials.gov Identifier: NCT02037555|
Recruitment Status : Completed
First Posted : January 16, 2014
Results First Posted : February 15, 2019
Last Update Posted : March 15, 2019
|Condition or disease||Intervention/treatment||Phase|
|Cardiac Surgery Cardiopulmonary Bypass||Biological: AT-III (Human) Other: Placebo||Phase 2|
The primary objective of this clinical study was to compare the percentage of subjects with any component of a 7 item major morbidity composite (postoperative mortality, stroke, acute kidney injury ([AKI]), surgical re-exploration, arterial or venous thromboembolic event, prolonged mechanical ventilation, or infection) between 2 groups of subjects randomly allocated to receive preoperative supplementation of AT-III (Human) (Antithrombin-III ([Human ]) or Placebo.
The secondary objectives of this clinical study were the following:
- To compare postoperative antithrombin III (AT) levels at the Intensive Care Unit (ICU) admission between the AT-III (Human) treatment group and Placebo control group
To compare the following perioperative outcomes between the AT-III (Human) treatment group and Placebo control group:
- Postoperative chest-drain blood loss in the first 12 and 24 hours after surgery
- Transfusion requirements
- Need for surgical re-exploration
- Low cardiac output syndrome
- Myocardial Infarction (MI)
- Arterial or venous thromboembolic events
- Prolonged mechanical ventilation (>24 hours)
- All-cause postoperative mortality
- ICU stay duration
- Prolonged ICU stay (>6 days)
- Length of hospital stay
Additionally, safety objectives included the evaluation of AT III (Human) for clinical safety including adverse events (AEs), risks for bleeding, clinical laboratory testing, physical exam, and vital signs.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||425 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Preoperative Antithrombin Supplementation in Patients Undergoing High-Risk Cardiac Surgery With Cardiopulmonary Bypass|
|Actual Study Start Date :||June 26, 2014|
|Actual Primary Completion Date :||January 25, 2018|
|Actual Study Completion Date :||January 25, 2018|
Experimental: AT-III (Human)
Single intravenous dose of AT-III (Human) sufficient to achieve an absolute increase of 20% (percentage points) above pretreatment AT levels according the following formula:
AT-III (Human) dose (IU) required = (20) × (subject weight in kg) / 1.4
Biological: AT-III (Human)
AT-III (Human) is an antithrombin concentrate prepared from pooled human plasma. AT-III (Human) is provided as a freeze-dried preparation for intravenous use. The AT-III (Human) preparation is reconstituted in 10 or 20 mL of sterile water for injection prior to intravenous administration.
Other Name: Antithrombin
Placebo Comparator: Placebo
Single intravenous administration of placebo at a volume equivalent to the volume for the calculated AT-III (Human) dose.
0.9% Sodium Chloride for Injection, United States Pharmacopeia
Other Name: Saline
- Percentage of Subjects With Any Component of a Major Morbidity Composite [ Time Frame: Up to Day 30 +/- 4 days ]
Major morbidity composite defined as a composite of any one or more of the following:
- Postoperative mortality (deaths occurring within 30 days of the operation or occurring during the primary hospitalization).
- Stroke (clinical diagnosis of focal or global neurological deficit of abrupt onset caused by disturbance in cerebral blood supply).
- Acute kidney injury (increase of serum creatinine levels to >2.0 mg/dL and twice the baseline level or a new requirement for dialysis postoperatively).
- Surgical reexploration (return to operating room because of bleeding, tamponade, graft occlusion or other cardiac reason).
- Arterial or venous thromboembolic event (perioperative myocardial or mesenteric infarction, peripheral thromboembolism, acute coronary graft thrombosis, intracardiac thrombosis, deep vein thrombosis, pulmonary embolism).
- Prolonged mechanical ventilation (>24 hours).
- Infection (deep sternal-wound infection and/or bloodstream infections).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02037555