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Cardiac SurgeryPhase 2NCT02037555

Safety and Efficacy of Preoperative Antithrombin Supplementation in Patients Undergoing High-Risk Cardiopulmonary Bypass

A Phase 2 study testing AT-III (Human) in people with Cardiac Surgery and Cardiopulmonary Bypass, run by Grifols Therapeutics LLC at 41 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cardiac Surgery, Cardiopulmonary Bypass
What is being tested?
AT-III (Human)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
425 participants
Where
41 sitesUnited States
Study dates
26 Jun 2014to 25 Jan 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%.
Show all 10Show fewer
  • 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.

Who cannot join

  • 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.
Show all 19Show fewer
  • 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.
  • Subject had allergies to excipients in the study drug.
  • Subject had refused to receive allogenic transfusion of blood-derived products.
  • Subject had received AT treatment within the last 3 months prior to Screening Visit.
  • Subject was pregnant. Subject had participated in any another investigational study within the last 3 months prior to Screening Visit.

Trial locations and contacts

41 sites in 1 country.

41 sites in 1 country

United States41 sites

  • Summa Health Hospital

    Akron, Ohio, 44304

  • Emory University Hospital

    Atlanta, Georgia, 30322

  • Georgia Regents University

    Augusta, Georgia, 30912

  • University of Colorado

    Aurora, Colorado, 80045

  • Memorial Hermann Memorial City Medical Center

    Bellaire, Texas, 77401

  • Brigham & Women's Hospital

    Boston, Massachusetts, 02115

  • The Lindner Center for Research & Education - The Christ Hospital

    Cincinnati, Ohio, 45219

  • University Hospitals Case Medical Center

    Cleveland, Ohio, 44106

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Sanford Health Fargo

    Fargo, North Dakota, 58103

  • Indiana Ohio Heart

    Fort Wayne, Indiana, 46804

  • University of Florida College of Medicine

    Gainesville, Florida, 32610

  • Texas Heart

    Houston, Texas, 77030

  • St. Vincent Heart Center of IN, LLC

    Indianapolis, Indiana, 46290

  • Saint Luke's Hospital

    Kansas City, Missouri, 64111

  • Sparrow Clinical Research Institute

    Lansing, Michigan, 48910

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03766

  • Kentucky Clinic

    Lexington, Kentucky, 40536

  • CHI Health Nebraska Heart Medical Office

    Lincoln, Nebraska, 68526

  • Baptist Memorial Hospital Memphis

    Memphis, Tennessee, 38120

  • Jackson Memorial Hospital at University of Miami

    Miami, Florida, 33136

  • St. Thomas Health

    Nashville, Tennessee, 37205

  • Yale University School of Medicine

    New Haven, Connecticut, 06510

  • North Shore University Hospital

    New Hyde Park, New York, 11040

  • Tulane University Medical

    New Orleans, Louisiana, 70112

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • UC Irvine

    Orange, California, 92868

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • UPMC Presbyterian Hospital

    Pittsburgh, Pennsylvania, 15213

  • Maine Medical Center

    Portland, Maine, 04102

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Cardiothoracic Surgical Associates

    Richmond, Virginia, 23225

  • Virginia Commonwealth University Medical Center

    Richmond, Virginia, 23298

  • William Beaumont Hospital

    Royal Oak, Michigan, 48073

  • VA Medical Center - San Francisco

    San Francisco, California, 94121

  • Memorial Medical Center

    Springfield, Illinois, 62794

  • Missouri Baptist Medical Center

    St Louis, Missouri, 63131

  • Stanford University Hospital and Clinics

    Stanford, California, 94305

  • ProMedica Toledo Hospital

    Toledo, Ohio, 43606

  • University of Toledo Medical Center

    Toledo, Ohio, 43614

Other trials in United States

About this study

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

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.

Read the detailed description

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)
  • Stroke
  • AKI
  • Arterial or venous thromboembolic events
  • Infections
  • 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.

Being tested
AT-III (Human), Placebo
Keywords
Antithrombin, Cardiopulmonary bypass

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AT-III (Human)Biological

    Also called Antithrombin

    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.

  • PlaceboOther

    Also called Saline

    0.9% Sodium Chloride for Injection, United States Pharmacopeia

Study groups in NCT02037555
Study groupRoleWhat they receive
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
Receives: Biological: AT-III (Human)
PlaceboPlacebo comparatorSingle intravenous administration of placebo at a volume equivalent to the volume for the calculated AT-III (Human) dose.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Up to Day 30 +/- 4 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jan 2014 (estimated)
  2. Study start26 Jun 2014
  3. Primary completion25 Jan 2018
  4. Study completion25 Jan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
425 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02037555
Sponsor's protocol ID
GTI1307
Status last verified
Feb 2019
First submitted
14 Jan 2014
Last updated
15 Mar 2019
Data monitoring committee
No

Publications

  • 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.

    PubMed 35877927

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AT-III (Human) in people with Cardiac Surgery and Cardiopulmonary Bypass, run by Grifols Therapeutics LLC at 41 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Subjects With Any Component of a Major Morbidity Composite (time frame: Up to Day 30 +/- 4 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02037555, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2019.

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