Use of Antithrombin in Cardiac Surgery With Cardiopulmonary Bypass

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Grifols Biologicals Inc. ( Instituto Grifols, S.A. )
ClinicalTrials.gov Identifier:
NCT00823082
First received: January 14, 2009
Last updated: June 23, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Acquired Antithrombin III Deficiency
Coronary Artery Bypass
Drug: Antithrombin III
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Grifols Biologicals Inc.:

Primary Outcome Measures:
  • Postoperative ATIII Levels at the ICU Admission [ Time Frame: ICU admission ] [ Designated as safety issue: No ]
    Measurement of postoperative ATIII functional activity at ICU admission

  • Percentage of Subjects With ATIII Levels of 58% or Higher at ICU Admission [ Time Frame: ICU admission ] [ Designated as safety issue: No ]
    Percentage of subjects with ATIII levels of 58% functional activity or higher at ICU admission


Secondary Outcome Measures:
  • Percentage of Subjects With Postoperative Myocardial Infarction [ Time Frame: During ICU stay (maximum 70 days) ] [ Designated as safety issue: Yes ]
    Percentage of subjects with postoperative myocardial infarction defined through enzymatic criteria plus new Q-waves at the electrocardiogram

  • Percentage of Subjects With Adverse Neurologic Outcome [ Time Frame: During ICU stay (maximum 70 days) ] [ Designated as safety issue: Yes ]
    Percentage of subjects with adverse neurologic outcome defined as: coma, stroke or psychotic behaviors lasting >12 hours after extubation

  • Percentage of Patients With Thromboembolic Events [ Time Frame: During ICU stay (maximum 70 days) ] [ Designated as safety issue: Yes ]
    Percentage of subjects with thromboembolic events defined as perioperative myocardial infarction, stroke, mesenteric infarction, peripheral thromboembolism and pulmonary embolism

  • ICU Stay Duration [ Time Frame: During ICU stay (maximum 70 days) ] [ Designated as safety issue: Yes ]
  • In-hospital Postoperative Mortality [ Time Frame: 70 days after ICU admission (maximum) ] [ Designated as safety issue: Yes ]
  • Heparin Resistance [ Time Frame: Immediately after anesthesia induction ] [ Designated as safety issue: No ]
    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

  • Postoperative Blood Loss in First 12 Hours [ Time Frame: ICU admission through 12 hours post-operative ] [ Designated as safety issue: Yes ]
    Blood loss defined as the amount of blood collected in the cardiotomy reservoir from ICU admission through the following 12 hours

  • Need for Blood Products [ Time Frame: During ICU stay (maximum 70 days) ] [ Designated as safety issue: Yes ]
    Number of units of packed red blood cells, fresh frozen plasma, and/or platelets needed

  • Percentage of Subjects Needing Surgical Re-exploration [ Time Frame: During ICU stay (maximum 70 days) ] [ Designated as safety issue: Yes ]
    Percentage of subjects needing surgical re-exploration resulting from bleeding

  • Percentage of Subjects With Low Cardiac Syndrome [ Time Frame: During ICU stay (maximum 70 days) ] [ Designated as safety issue: Yes ]
    Percentage of subjects with low cardiac syndrome defined as the need for major inotropic support or intra-aortic balloon pump

  • Percentage of Subjects With Renal Dysfunction [ Time Frame: During ICU stay (maximum 70 days) ] [ Designated as safety issue: Yes ]
    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

  • Mechanical Ventilation Duration [ Time Frame: During ICU stay (maximum 70 days) ] [ Designated as safety issue: Yes ]
  • Length of Hospital Stay [ Time Frame: During ICU stay (maximum 70 days) ] [ Designated as safety issue: No ]
    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.


Enrollment: 200
Study Start Date: June 2009
Study Completion Date: September 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Antithrombin III treatment group
Preoperative ATIII supplementation administered immediately after anesthesia induction
Drug: Antithrombin III
Single dose of antithrombin III sufficient to achieve a preoperative level of 120%
Other Names:
  • Anbinex
  • ATIII
No Intervention: Control group
No preoperative ATIII supplementation administered

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00823082

Locations
Italy
IRCCS Policlinico San Donato
Milano, Lombardy, Italy, 20097
Sponsors and Collaborators
Instituto Grifols, S.A.
Investigators
Principal Investigator: Marco Ranucci, MD IRCCS Policlinico San Donato, Milano
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Instituto Grifols, S.A.
ClinicalTrials.gov Identifier: NCT00823082     History of Changes
Other Study ID Numbers: IG0801 
Study First Received: January 14, 2009
Results First Received: April 5, 2016
Last Updated: June 23, 2016
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Grifols Biologicals Inc.:
antithrombin
ATIII
acquired deficiency
anticoagulants
cardiopulmonary bypass
surgery
complications
postoperative outcomes

Additional relevant MeSH terms:
Antithrombin III Deficiency
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Blood Protein Disorders
Thrombophilia
Genetic Diseases, Inborn
Antithrombins
Antithrombin III
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants

ClinicalTrials.gov processed this record on August 25, 2016