Antithrombin Enhancement May Improve Anticoagulation Efficiency in Infants Undergoing Cardiopulmonary Bypass for Cardiac Surgery

Study Overview
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Brief Summary
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The primary objective of this study is: 1. To evaluate the use of Antithrombin (AT) concentrate in infants less than one year of age undergoing cardiopulmonary bypass (CPB) for cardiac surgery The secondary objectives of this study are: To determine if the administration of AT concentrate prior to heparinization will decrease the amount of heparin required to achieve optimal anticoagulation (as defined by anti-Xa levels) during CPB To determine if a decrease in activation and consumption of coagulation proteins, platelets and subsequent fibrinolysis will result in improved haemostasis following CPB To determine if there will be a reduction in postoperative bleeding and associated clinical complications

Official Title
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Antithrombin Enhancement May Improve Anticoagulation Efficiency in Infants Undergoing Cardiopulmonary Bypass for Cardiac Surgery

Conditions
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Cardiopulmonary Bypass

Intervention / Treatment
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* Drug: Antithrombin III
* Other: Saline Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric patients < 1 year old with cardiac defect (acquired or congenital) requiring cardiac surgery Planned cardiac surgery with cardiopulmonary bypass Weight > 2.5kg at the time of surgery Enrolment in the CATCH main study (REB#1000020203) Exclusion Criteria: Preoperative antithrombin activity > 85% Prematurity < 36 weeks gestational age at birth Preoperative use of systemic anticoagulant (i.e. heparin or warfarin at a therapeutic dose) for > 24 hours or at any time within the 48 hours prior to surgery Any form of coagulopathy or thrombophilic disorder Renal (blood creatinine - estimated GRF < 60ml/min/1.73m2) or clinical liver failure Antithrombin replacement therapy prior to surgery Repeat surgery (including previous ECMO/VAD support as prior surgery) Patients refusal to provide open consent for re-use of study data

Ages Eligible for Study
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Maximum Age: 364 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control Group<br> | Other: Saline Placebo<br>* Patients randomized to the control group will receive a placebo consisting of normal saline in a volume equivalent to the volume of antithrombin the same patient in the treatment group would have received and administered by anesthesia and perfusion in the exact same manner as the AT is administered in the treatment group.<br>|
| Experimental: Active Antithrombin Group<br> | Drug: Antithrombin III<br>* Patients randomized to receive Antithrombin concentrate will receive a dose of AT to achieve a target value of 1.2U/ml.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chest tube volume loss | Chest tube volume loss (mls/kg) at 24 hours in CCCU | 24 hrs post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heparin dose required to achieve target Activated Clotting Time required to go on Cardiopulmonary Bypass | Clinical Outcome Measure | 1hr prior to induction of anaestheisa (pre-surgery) | 
| Blood product transfusions intra-operatively and for the first 24 hours following surgery |  | 24hours post surgery | 
| Clinical outcomes | (inotropic support, ventilation, CCU stay, hospital stay, thrombosis) | 30 days post-surgery | 
| Intraoperative coagulation profile | (anti-Xa, heparin concentration, activated clotting time, CBC, antithrombin) | 5 hours after start of surgery | 
| Post-operative markers of platelet activation | Post-operative markers of platelet activation (TAT, F1.2), fibrinolysis (d-dimer) and inflammation (CRP) | 24 and 72 hrs post surgery | 
| Use of recombinant factor VIIa after surgery to control post-operative bleeding |  | 48 hrs post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric, Antithrombin, anticoagulation efficiency, cardiac surgery