Evaluation Of The Pharmacokinetics Of Antithrombin III In Neonates And Infants Undergoing CPB And ECMO Support
| Status: | Completed |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | Any - 1 |
| Updated: | 1/27/2019 |
| Start Date: | June 2015 |
| End Date: | June 2018 |
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.
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.
This is a single-site, prospective, open-label, pharmacokinetic study of hpATIII in neonates
and infants. Patients admitted to the Cardiac Intensive Care Unit (CICU) and the Neonatal
Intensive Care Unit (NICU) at Cincinnati Children's Hospital Medical Center (CCHMC) will be
enrolled. Participants will be enrolled into one of three cohorts depending on whether they
are scheduled for ECMO, CPB, or neither, and based on age (neonate or infant).
Two doses of hpATIII will be used; one according to current labelling for hpATIII and one
that accounts for the additional circuit volume from ECMO or CPB. Pharmacokinetic
measurements will be obtained for all groups at baseline prior to administration of hpATIII
and at multiple defined times up to 120 hrs following each administration of hpATIII.
Administration of hpATIII is standard of care at CCHMC for participants undergoing ECMO. The
standard dose administered for clinical care is (120 - baseline AT activity level) x weight
(kg) / 1.4. For participants not undergoing ECMO for clinical care, or for those undergoing
ECMO but receiving an adjusted dose for additional circuit volume , the administration of
hpATIII is considered research.
The duration of the study at CCHMC is expected to be 2.5 years. This includes 24 months for
recruitment and data collection, and 6 months for data analysis and report writing.
Individual participants will be in the study for approximately 120 hours (5 days) following
administration of hpATIII. If participants receive more than 1 dose, they will be in the
study for approximately 120 hours following each dose of hpATIII received.
and infants. Patients admitted to the Cardiac Intensive Care Unit (CICU) and the Neonatal
Intensive Care Unit (NICU) at Cincinnati Children's Hospital Medical Center (CCHMC) will be
enrolled. Participants will be enrolled into one of three cohorts depending on whether they
are scheduled for ECMO, CPB, or neither, and based on age (neonate or infant).
Two doses of hpATIII will be used; one according to current labelling for hpATIII and one
that accounts for the additional circuit volume from ECMO or CPB. Pharmacokinetic
measurements will be obtained for all groups at baseline prior to administration of hpATIII
and at multiple defined times up to 120 hrs following each administration of hpATIII.
Administration of hpATIII is standard of care at CCHMC for participants undergoing ECMO. The
standard dose administered for clinical care is (120 - baseline AT activity level) x weight
(kg) / 1.4. For participants not undergoing ECMO for clinical care, or for those undergoing
ECMO but receiving an adjusted dose for additional circuit volume , the administration of
hpATIII is considered research.
The duration of the study at CCHMC is expected to be 2.5 years. This includes 24 months for
recruitment and data collection, and 6 months for data analysis and report writing.
Individual participants will be in the study for approximately 120 hours (5 days) following
administration of hpATIII. If participants receive more than 1 dose, they will be in the
study for approximately 120 hours following each dose of hpATIII received.
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;
We found this trial at
1
site
3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
Cincinnati, Ohio 45229
1-513-636-4200
Phone: 513-803-9002
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
Click here to add this to my saved trials
