Safety and Efficacy of Preoperative Antithrombin Supplementation in Patients Undergoing High-Risk Cardiopulmonary Bypass
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
1 other identifier
interventional
425
1 country
41
Brief Summary
This is a prospective, multicenter, randomized, double-blind, placebo-controlled study. The purpose of this study is to determine the safety and effectiveness of human-derived antithrombin III (AT-III \[Human\]) supplementation prior to high-risk, non-emergency, cardiac surgery with cardiopulmonary bypass (CPB). A total of 404 adult subjects undergoing CPB who meet the study eligibility criteria were planned to be randomized to receive either AT-III (Human) or placebo.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2014
Typical duration for phase_2
41 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 14, 2014
CompletedFirst Posted
Study publicly available on registry
January 16, 2014
CompletedStudy Start
First participant enrolled
June 26, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 25, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
January 25, 2018
CompletedResults Posted
Study results publicly available
February 15, 2019
CompletedMarch 15, 2019
February 1, 2019
3.6 years
January 14, 2014
January 24, 2019
February 27, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Subjects With Any Component of a Major Morbidity Composite
Major morbidity composite defined as a composite of any one or more of the following: 1. Postoperative mortality (deaths occurring within 30 days of the operation or occurring during the primary hospitalization). 2. Stroke (clinical diagnosis of focal or global neurological deficit of abrupt onset caused by disturbance in cerebral blood supply). 3. 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). 4. Surgical reexploration (return to operating room because of bleeding, tamponade, graft occlusion or other cardiac reason). 5. Arterial or venous thromboembolic event (perioperative myocardial or mesenteric infarction, peripheral thromboembolism, acute coronary graft thrombosis, intracardiac thrombosis, deep vein thrombosis, pulmonary embolism). 6. Prolonged mechanical ventilation (\>24 hours). 7. Infection (deep sternal-wound infection and/or bloodstream infections).
Up to Day 30 +/- 4 days
Study Arms (2)
AT-III (Human)
EXPERIMENTALSingle 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
Placebo
PLACEBO COMPARATORSingle intravenous administration of placebo at a volume equivalent to the volume for the calculated AT-III (Human) dose.
Interventions
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.
0.9% Sodium Chloride for Injection, United States Pharmacopeia
Eligibility Criteria
You may qualify if:
- Male or female.
- At least 18 years of age.
- Subject needed non-emergency cardiac surgery with CPB.
- Types of cardiac operations permitted: complex/combined procedures (CABG+valve), double/triple valve repair/replacement, ascending aorta/aortic arch surgeries. Isolated CABG or single valve repair/replacements were allowed only if subject had received preoperative heparin \>2 days.
- \- Following the incorporation of Protocol Version 4.0 (Amendment 3 dated 02 Apr 2015), this criterion was revised to include complex/combined procedures (CABG+valve), double/triple valve repair/replacements, ascending aorta/aortic arch surgeries (without baseline AT level restriction or preoperative heparin requirement). OR isolated CABG or single valve repair/replacements were allowed only if either (a) AT level was less than 80% OR (b) preoperative heparin was received (\[UFH for at least 12 hours; LMWH for more than 5 days).
- Subject had a baseline AT level of less than 80%.
- Following incorporation of Protocol Version 3.0 (Amendment 2 dated 02 Sep 2014) this was changed to Subject had a Prescreening/Screening and baseline local lab AT level of less than 80%.
- Following the incorporation of Protocol Version 4.0 (Amendment 3 dated 02 Apr 2015) this criterion was deleted and noted as "Not applicable - intentionally left blank for data management purposes (consistency in eCRF capture of eligibility criteria historically)."
- Subject had signed informed consent form.
- Subject was willing to comply with all aspects of the protocol, including blood sampling, for the total duration of the study.
You may not qualify if:
- Subject needed emergency surgery.
- Subject needed heart transplantation.
- Subject needed the use of minimally invasive surgery.
- Subject had previous cardiac operation.
- Subject had infective endocarditis.
- Subject had thromboembolic events, stroke, or ST-elevated MI within 7 days of surgery.
- Subject had cardiogenic shock at the time of surgery.
- Subject had renal dysfunction: creatinine levels \>2 mg/dL or chronic dialysis.
- Subject had liver dysfunction: aspartate aminotransferase (AST), alanine aminotransferase (ALT) increase ≥2-fold above the upper-limit of local lab normal ranges.
- Subject had treatment with Clopidogrel® and Ticagrelor® within 5 days before surgery, Prasugrel® within 7 days before surgery, glycoprotein IIb/IIIa receptor blockers within 24 hours of surgery.
- Subject had treatment with new oral anticoagulants (Apixaban®, Rivaroxaban®, Dabigatran®) within 48 hours before surgery.
- Subject had Vitamin K antagonist therapy and an international normalized ratio (INR) \>1.3 on the day of surgery.
- Subject had platelet count \<120,000/μL.
- Subject had history or suspicion of a congenital or acquired coagulation disorder.
- Subject had history of anaphylactic reaction(s) to blood or blood components.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Grifols Therapeutics LLClead
- Covancecollaborator
- Clinipace Worldwidecollaborator
Study Sites (41)
UC Irvine
Orange, California, 92868, United States
VA Medical Center - San Francisco
San Francisco, California, 94121, United States
Stanford University Hospital and Clinics
Stanford, California, 94305, United States
University of Colorado
Aurora, Colorado, 80045, United States
Yale University School of Medicine
New Haven, Connecticut, 06510, United States
University of Florida College of Medicine
Gainesville, Florida, 32610, United States
Jackson Memorial Hospital at University of Miami
Miami, Florida, 33136, United States
Emory University Hospital
Atlanta, Georgia, 30322, United States
Georgia Regents University
Augusta, Georgia, 30912, United States
Memorial Medical Center
Springfield, Illinois, 62794, United States
Indiana Ohio Heart
Fort Wayne, Indiana, 46804, United States
St. Vincent Heart Center of IN, LLC
Indianapolis, Indiana, 46290, United States
Kentucky Clinic
Lexington, Kentucky, 40536, United States
Tulane University Medical
New Orleans, Louisiana, 70112, United States
Maine Medical Center
Portland, Maine, 04102, United States
Brigham & Women's Hospital
Boston, Massachusetts, 02115, United States
Sparrow Clinical Research Institute
Lansing, Michigan, 48910, United States
William Beaumont Hospital
Royal Oak, Michigan, 48073, United States
Saint Luke's Hospital
Kansas City, Missouri, 64111, United States
Missouri Baptist Medical Center
St Louis, Missouri, 63131, United States
CHI Health Nebraska Heart Medical Office
Lincoln, Nebraska, 68526, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03766, United States
North Shore University Hospital
New Hyde Park, New York, 11040, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Sanford Health Fargo
Fargo, North Dakota, 58103, United States
Summa Health Hospital
Akron, Ohio, 44304, United States
The Lindner Center for Research & Education - The Christ Hospital
Cincinnati, Ohio, 45219, United States
University Hospitals Case Medical Center
Cleveland, Ohio, 44106, United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210, United States
ProMedica Toledo Hospital
Toledo, Ohio, 43606, United States
University of Toledo Medical Center
Toledo, Ohio, 43614, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
UPMC Presbyterian Hospital
Pittsburgh, Pennsylvania, 15213, United States
Baptist Memorial Hospital Memphis
Memphis, Tennessee, 38120, United States
St. Thomas Health
Nashville, Tennessee, 37205, United States
Memorial Hermann Memorial City Medical Center
Bellaire, Texas, 77401, United States
Texas Heart
Houston, Texas, 77030, United States
Cardiothoracic Surgical Associates
Richmond, Virginia, 23225, United States
Virginia Commonwealth University Medical Center
Richmond, Virginia, 23298, United States
Related Publications (1)
Moront MG, Woodward MK, Essandoh MK, Avery EG, Reece TB, Brzezinski M, Spiess B, Shore-Lesserson L, Chen J, Henriquez W, Barcelo M, Despotis G, Karkouti K, Levy JH, Ranucci M, Mondou E; Clinical Thrombate Study Group. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Preoperative Antithrombin Supplementation in Patients at Risk for Antithrombin Deficiency After Cardiac Surgery. Anesth Analg. 2022 Oct 1;135(4):757-768. doi: 10.1213/ANE.0000000000006145. Epub 2022 Jul 25.
PMID: 35877927DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Miquel Barceló, PhD
- Organization
- Grifols Therapeutics, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 14, 2014
First Posted
January 16, 2014
Study Start
June 26, 2014
Primary Completion
January 25, 2018
Study Completion
January 25, 2018
Last Updated
March 15, 2019
Results First Posted
February 15, 2019
Record last verified: 2019-02