Evaluation Of The Pharmacokinetics Of Antithrombin III In Neonates And Infants Undergoing CPB And ECMO Support

• Status: Completed
• Trial end date: 2018-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The potential role of ATIII in achieving and maintaining adequate anticoagulation in pediatric patients on the heart-lung machine has recently taken on increased importance as caregivers strive to mitigate the risk for clinically significant clotting problems. It is known that ATIII levels are decreased in normal neonates and infants less than 6 months of age relative to older children and adults and become even further decreased in critically ill neonates and infants, including those with congenital heart disease. The current utilization of ATIII in the context of support on a heart-lung machine is based on pharmacokinetic data derived from adult subjects with congenital ATIII deficiency. There is a gap in knowledge as to the appropriate frequency of ATIII repletion, best method of monitoring, and mode of administration in critically ill neonates and infants receiving support on a heart-lung machine.Our long-term goal is to determine if antithrombin (ATIII) can effectively change the coagulation system in patients undergoing heart-lung machine support. The objective of this proposal, which is our first step in pursuit of that goal, is to determine the pharmacokinetics of ATIII in neonates and infants. Our central hypothesis is that ATIII will have different pharmacokinetic properties in neonates and infants than adults and these properties will be affected by the use of heart-lung machine.

This research will result in critical data on the pharmacokinetics of ATIII in neonates and infants receiving heart-lung machine support. This contribution is significant because it is the first step in a continuum of research that is expected to lead to the development of a therapeutic strategy employing ATIII that will facilitate improved modulation of the coagulation cascade to prevent significant clotting and bleeding complications in pediatric patients requiring heart-lung machine support.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: Grifols Biologicals Inc.; Grifols Biologicals, LLC
• Treatments: Antithrombin III; Antithrombins

Criteria

Inclusion Criteria:

• 1. Neonates less than or equal to 28 days of age OR Infants between 29 days and 1 year of age;

• 2. ATIII activity less than 80% at time of screening;

Exclusion Criteria:

• Subjects who meet any of the following criteria will be excluded from the study:

1. Known or suspected bleeding disorder;

2. Neonates with gestational age <36 weeks;

3. Neonates with evidence of intracranial hemorrhage on routine cranial ultrasound;

4. Documented infection (sepsis);

5. Patients who require post-cardiotomy ECMO;

6. Patients who require E-CPR; and/or

7. Neonates or infants deemed to be at increased risk as judged by the investigator or for whom administration of hpATIII is not in their best interest

8. Additional Exclusion for Cohort 1 only: Transfusion of whole blood, fresh frozen plasma (FFP), platelets or cryoprecipitate prior to study;