Use of Antithrombin in Cardiac Surgery With Cardiopulmonary Bypass

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

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Bypass; Acquired Antithrombin III Deficiency
• Intervention / Treatment: Drug: Antithrombin III

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Lombardy
    • Milano, Lombardy, Italy, 20097
      • IRCCS Policlinico San Donato

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Instituto Grifols, S.A.
• Investigators: Principal Investigator: Marco Ranucci, MD, IRCCS Policlinico San Donato, Milano

Publications and helpful links

General Publications

• Ranucci M, Baryshnikova E, Crapelli GB, Woodward MK, Paez A, Pelissero G. Preoperative antithrombin supplementation in cardiac surgery: a randomized controlled trial. J Thorac Cardiovasc Surg. 2013 May;145(5):1393-9. doi: 10.1016/j.jtcvs.2012.09.061. Epub 2012 Oct 25.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: January 14, 2009
• First Submitted That Met QC Criteria: January 14, 2009
• First Posted (Estimate): January 15, 2009

Study Record Updates

• Last Update Posted (Estimate): September 20, 2016
• Last Update Submitted That Met QC Criteria: August 10, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: surgery; complications; cardiopulmonary bypass; anticoagulants; antithrombin; ATIII; acquired deficiency; postoperative outcomes
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Genetic Diseases, Inborn; Blood Protein Disorders; Blood Coagulation Disorders; Thrombophilia; Antithrombin III Deficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Anticoagulants; Antithrombins; Antithrombin III
• Other Study ID Numbers: IG0801