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

• ClinicalTrials.gov Identifier: NCT01530737
• Recruitment Status: Completed
• First Posted: February 10, 2012
• Last Update Posted: January 7, 2015
• Sponsor: The Hospital for Sick Children
• Information provided by (Responsible Party): Brian McCrindle, The Hospital for Sick Children

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Cardiopulmonary Bypass	Drug: Antithrombin III; Other: Saline Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Antithrombin Enhancement May Improve Anticoagulation Efficiency in Infants Undergoing Cardiopulmonary Bypass for Cardiac Surgery
• Study Start Date: November 2011
• Actual Primary Completion Date: October 2014
• Actual Study Completion Date: October 2014

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Chest tube volume loss [ Time Frame: 24 hrs post surgery ]
   Chest tube volume loss (mls/kg) at 24 hours in CCCU

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: up to 364 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Canada, Ontario

The Hospital for Sick Children

Toronto, Ontario, Canada, M5V1X8

Sponsors and Collaborators

The Hospital for Sick Children

Investigators

• Principal Investigator: Brian W McCrindle, MD; The Hospital for Sick Children

More Information

• Responsible Party: Brian McCrindle, Staff Cardiologist, The Hospital for Sick Children
• ClinicalTrials.gov Identifier: NCT01530737
• Other Study ID Numbers: 1000020202
• First Posted: February 10, 2012
• Last Update Posted: January 7, 2015
• Last Verified: January 2015

Keywords provided by Brian McCrindle, The Hospital for Sick Children:

pediatric; Antithrombin; anticoagulation efficiency; cardiac surgery

Additional relevant MeSH terms:

Antithrombins; Antithrombin III; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants