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

Duke University45 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

ATIII Deficiency

Interventions

Anti-thrombin IIIDRUG

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

PlaceboOTHER

Normal saline placebo

Eligibility

Sex: ALLMax age: 7 Months

Medical Language ↔ Plain English

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

Locations (1)

Duke University

Durham, North Carolina, United States

Outcomes

Primary Outcomes

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)

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).

Time frame: Time 5 (on arrival in ICU)

Secondary Outcomes

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)

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)

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

Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at 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.

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

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

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.

Data from ClinicalTrials.gov

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

Difference in the Median of the D Dimer of the Control and ATIII Groups at 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).

Time frame: T1, T5, T6 and T7

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

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.

Time frame: T5 (Intensive Care Unit Arrival)

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

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)

Total Dose of Heparin While on Cardiopulmonary Bypass

Total dose of Heparin while on Cardiopulmonary Bypass

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

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

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

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

Total Volume of Blood Products While on CPB

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

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

Time From Protamine Administration to Skin Dressing

Time from protamine administration to skin dressing

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

Total Volume of Fresh Frozen Plasma Given Prior to CPB

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

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

Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively

Time frame: Baseline (Intraoperatively)

Volume of Postoperative Blood Loss

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

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

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

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

Time frame: protamine time plus 24 hours

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

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)

Time frame: 24 Hours Post-Operatively

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

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)

Time frame: 24 Hours Post-Operatively

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

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

Time frame: Intraoperatively

Length of Post Operative Ventilation in Days

Length of post operative ventilation in days

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

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

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