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

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:

1. 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
2. To determine if a decrease in activation and consumption of coagulation proteins, platelets and subsequent fibrinolysis will result in improved haemostasis following CPB
3. To determine if there will be a reduction in postoperative bleeding and associated clinical complications

Study Overview

• Status: Completed
• Conditions: Cardiopulmonary Bypass
• Intervention / Treatment: Other: Saline Placebo; Drug: Antithrombin III

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5V1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 11 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Pediatric patients < 1 year old with cardiac defect (acquired or congenital) requiring cardiac surgery
2. Planned cardiac surgery with cardiopulmonary bypass
3. Weight > 2.5kg at the time of surgery
4. Enrolment in the CATCH main study (REB#1000020203)

Exclusion Criteria:

1. Preoperative antithrombin activity > 85%
2. Prematurity < 36 weeks gestational age at birth
3. 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
4. Any form of coagulopathy or thrombophilic disorder
5. Renal (blood creatinine - estimated GRF < 60ml/min/1.73m2) or clinical liver failure
6. Antithrombin replacement therapy prior to surgery
7. Repeat surgery (including previous ECMO/VAD support as prior surgery)
8. Patients refusal to provide open consent for re-use of study data

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Control Group	Other: Saline Placebo; 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.
EXPERIMENTAL: Active Antithrombin Group	Drug: Antithrombin III; Patients randomized to receive Antithrombin concentrate will receive a dose of AT to achieve a target value of 1.2U/ml.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: January 30, 2012
• First Submitted That Met QC Criteria: February 7, 2012
• First Posted (ESTIMATE): February 10, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 7, 2015
• Last Update Submitted That Met QC Criteria: January 6, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: cardiac surgery; pediatric; Antithrombin; anticoagulation efficiency
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Anticoagulants; Antithrombins; Antithrombin III
• Other Study ID Numbers: 1000020202