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OpenTrials
Completed

NCT Number: NCT02103114

Anti-thrombin III (ATIII) vs Placebo in Children (<7mo) Undergoing Open Congenital Cardiac Surgery

The purpose of this study is to test whether the administration of ATIII during the intra-operative period results in improved anticoagulation for cardiopulmonary bypass (CPB) and an attenuation of the activation of the coagulation cascade, as represented by a decrease in fibrin degradation products. The investigators believe this benefit would extend into the post-operative period resulting in a decreased incidence of thrombosis generation, as represented by a decrease in fibrin degradation products in the ICU period.

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Key information

Conditions

ATIII Deficiency

Age range

Up to 7 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Duke University

Durham, North Carolina, 27708, United States

About this study

If Preoperative ATIII functional assay level is less than 70% patients would be enrolled and randomized to either Placebo (normal saline) or ATIII.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • All patients less than 7 months of age going for cardiac surgery that will require cardiopulmonary bypass (CPB) with a documented ATIII level below 70%

Exclusion criteria

  • Less than 2.5kg
  • Known or suspected hereditary ATIII deficiency (family history of venous thrombosis with decreased plasma levels of ATIII and no other potential causes of acquired decreased ATIII)
  • On Ecmo (extracorporeal membrane oxygenation ) at time of surgery
  • Known history of thrombosis
  • Renal failure as described by the pediatric RIFLE criteria
  • H/o intracranial hemorrhage
  • Prematurity less than 37 weeks estimated gestational age
  • Previously diagnosed pro-thrombotic or hemorrhagic disorder
  • Prior ATIII supplementation
  • Prior therapeutic anticoagulant use

Treatment and study plan

Anti-thrombin III

Drug

Intraoperatively- (correcting to 100%) according to the following formula:

Units required = ((100%- baseline ATIII level*%) X body weight)/1.4

  • expressed as a % normal level based on functional ATIII assay

Other names: Thrombate III

Placebo

Other

Normal saline placebo

Primary outcomes

  1. Difference in the Mean and Standard Deviation (SD) of the Calibrated Automated Thrombography (CAT) Measurements of the Control and ATIII Groups at Time 5 (on Arrival in ICU)

    Time frame: Time 5 (on arrival in ICU)

    Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean and Standard Deviation (SD) of the Calibrated Automated Thrombography (CAT) measurements of the control and ATIII groups at Time 5 (on arrival in ICU).

Secondary outcomes

  1. Difference in the Mean and SD of the Calibrated Automated Thrombography (CAT) Measurements of the Control and ATIII Groups at Times 5-Time 7 (ICU Arrival to Post Operative Day 4)

    Time frame: ICU arrival (Time 5) to Time 7 (Post-operative Day 4)

    Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean and SD of the Calibrated Automated Thrombography (CAT) measurements of the control and ATIII groups at times 5-Time 7 (ICU arrival to Post Operative Day 4)

  2. Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7

    Time frame: T1, T2, T3, T5, T6 and T7

    Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean of the ATIII (functional assay) of the control and ATIII groups at T1, T2, T3, T5, T6 and T7 (Baseline, 30 min after study drug, 30 min on CPB, Arrival in ICU, POD 2, and POD 4). Data reported as % Functional Activity, which is calculated as the ability of Antithrombin (AT) to suppress FIIa or FXa in the presence of heparin compared to normograms, and expressed as a percentage.

  3. Difference in the Median of the ATIII (Functional Assay) of the Control and ATIII Groups at T4

    Time frame: T4 (just prior to coming off of CPB)

    Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the median of the ATIII (functional assay) of the control and ATIII groups at T4 (just prior to coming off of CPB). Data reported as % Functional Activity, which is calculated as the ability of Antithrombin (AT) to suppress FIIa or FXa in the presence of heparin compared to normograms, and expressed as a percentage.

  4. Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7

    Time frame: T1, T5, T6 and T7

    Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the median of the D dimer of the control and ATIII groups at T1 (Baseline), T5 (Arrival in Intensive Care Unit), T6 (Post-Operative Day 2) and T7 (Post-Operative Day 4).

  5. Residual Heparin at the ICU Arrival Time Point Represented by a Decreased Anti Factor Xa Level.

    Time frame: T5 (Intensive Care Unit Arrival)

    Evidence of a decreased amount of residual heparin at the Intensive Care Unit arrival time point (T5) represented by a decreased anti factor Xa level.

  6. Evidence of Decreased Inflammation Represented by a Decrease in Inflammatory Markers in the ATIII Group

    Time frame: Baseline (T1) to Post-Operative Day 4 (T7)

    Evidence of decreased inflammation represented by a decrease in inflammatory markers in the ATIII group.

  7. Total Dose of Heparin While on Cardiopulmonary Bypass

    Time frame: T1 (Baseline) to T5 (Arrival in ICU)

    Total dose of Heparin while on Cardiopulmonary Bypass

  8. Protamine Dose Determined by Hemostasis Management System Machine (mg/kg)

    Time frame: T1 (Baseline) to T5 (Arrival in ICU)

    Protamine dose determined by Hemostasis Management system machine (mg/kg)

  9. Total Volume of Blood Products While on CPB

    Time frame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)

    Total volume of blood products exposed intraoperatively including the pump prime (ml/kg)

  10. Time From Protamine Administration to Skin Dressing

    Time frame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)

    Time from protamine administration to skin dressing

  11. Total Volume of Fresh Frozen Plasma Given Prior to CPB

    Time frame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)

    Total volume of Fresh Frozen Plasma given prior to CPB, including the pump prime (ml/kg)

  12. Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively

    Time frame: Baseline (Intraoperatively)

    Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively

  13. Volume of Postoperative Blood Loss

    Time frame: From 10min post protamine administration to 24 hour post protamine administration

    Volume of postoperative blood loss from 10min post protamine administration to 24 hour post protamine administration- (ml/kg)

  14. Chest Tube Output (Protamine Time Plus 24 Hours) in Milliliters

    Time frame: protamine time plus 24 hours

    Chest Tube output (protamine time plus 24 hours) in milliliters

  15. Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group

    Time frame: 24 Hours Post-Operatively

    Number of packed Fresh frozen plasma units, Platelet Units, cryo-precipitate units, and Red Blood Cell units transfused 24 hours post-operatively for each group (not total units transfused for each subject)

  16. Number of Total Blood Product Units Transfused 24-hours Post-operatively by Group

    Time frame: 24 Hours Post-Operatively

    Number of total blood product units (including packed Fresh frozen plasma units, Platelet Units, cryo-precipitate units, and Red Blood Cell units) transfused 24 hours post-operatively for each group (not total units transfused for each subject)

  17. Total Dose of Recombinant Factor 7a (VIIa) Used Intraoperatively

    Time frame: Intraoperatively

    Total Dose of rescue recombinant factor 7a (VIIa) used intraoperatively

  18. Length of Post Operative Ventilation in Days

    Time frame: ICU arrival (Time 5) to Time 7 (Post-Operative Day 4)

    Length of post operative ventilation in days

  19. Incidence of Extracorporeal Membrane Oxygenation (ECMO) Support Within 24 Hours Postoperatively

    Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)

    Study the safety profile of dosing the ATIII by monitoring the incidence of extracorporeal membrane oxygenation (ECMO) support within 24 hours postoperatively.

  20. Incidence of Mediastinal Exploration Within 24 Hours Postoperatively

    Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)

    Study the safety profile of dosing the ATIII by monitoring the incidence of mediastinal exploration within 24 hours postoperatively

  21. Incidence (Number) of Thrombotic Events Documented

    Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)

    Study the safety profile of dosing the ATIII by monitoring the incidence (number) of thrombotic events documented.

  22. Incidence of New Onset Renal Failure, Defined by Stage 3 of the AKIN Criteria

    Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)

    Study the safety profile of dosing the ATIII by monitoring the incidence of new onset renal failure, defined by stage 3 of the Acute Kidney Injury Network (AKIN) criteria.

    • Serum creatinine increase ≥26.5 μmol/l (≥0.3 mg/dl) or increase to 1.5-2.0-fold from baseline, urine output <0.5 ml/kg/h for 6 hours
    • Serum creatinine increase >2.0-3.0-fold from baseline, urine output <0.5 ml/kg/h for 12 hours
    • Serum creatinine increase >3.0-fold from baseline or serum creatinine ≥354 μmol/l (≥4.0 mg/dl) with an acute increase of at least 44 μmol/l (0.5 mg/dl) or need for Renal replacement therapy (RRT), urine output <0.3 ml/kg/h for 24 h or anuria for 12 hours or need for RRT

  23. Incidence (Number) of Newly Diagnosed Intracranial Hemorrhage

    Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)

    Study the safety profile of dosing the ATIII by monitoring the incidence (number) of newly diagnosed intracranial hemorrhage

  24. Length of Time to Delayed Sternal Closure Measured in Days

    Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)

    Study the safety profile of dosing the ATIII by monitoring the length of time to delayed sternal closure measured in days

Sponsors and collaborators

Lead sponsor

Duke University

Other

Collaborators

  • Grifols Biologicals, LLC

Registry information

Official study title

Double Blind Randomized Placebo-controlled Study in Children (<6mo) Comparing the Effects of Anti-thrombin III (ATIII) or Placebo on the Coagulation System in Infants With Known Low ATIII Levels Undergoing Open Congenital Cardiac Surgery

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Apr 3, 2014
Registry last updated
Nov 25, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.