In Vivo Effects of Fibrinogen Concentrate (FC) Versus Cryoprecipitate on the Neonatal Fibrin Network Structure After Cardiopulmonary Bypass (CPB)

Sponsor

Emory University (Other)

Overall Status

Completed

CT.gov ID

NCT03932240

Collaborator

(none)

Enrollment

Location

Arms

27.1

Actual Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This primary aim of this study is to compare the in vivo effects of fibrinogen concentrate and cryoprecipitate on the neonatal fibrin network after surgery with cardiopulmonary bypass to develop effective and safe strategies for managing coagulopathies in neonates.

Condition or Disease	Intervention/Treatment	Phase
Hemostasis	Drug: Fibrinogen Concentrate (FC) Drug: Cryoprecipitate	Phase 3

Detailed Description

This study is a prospective, randomized control trial comparing two different sources of fibrinogen on clot kinetics (degradation time, structure, strength and polymerization) in post-CPB coagulopathy in neonates undergoing cardiac surgery. The two sources of fibrinogen include the blood product, cryoprecipitate, and a blood product alternative, fibrinogen concentrate. Cryoprecipitate is an allogenic blood product that requires cross-matching and thawing prior to administration and is associated with immunologic reactions and possible pathogen transmission. Fibrinogen concentrate, a blood product alternative, is a purified form of fibrinogen, which undergoes a pasteurization process to minimize the risk of immunologic and allergic reactions. The primary aim of this study is compare the in vivo effect of post-CPB administration of FC, a blood product alternative, to cryoprecipitate on neonatal clot properties and clinical outcomes.

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

In Vivo Effects of Fibrinogen Concentrate (FC) Versus Cryoprecipitate on the Neonatal Fibrin Network Structure After Cardiopulmonary Bypass (CPB)

Actual Study Start Date :

Aug 13, 2019

Actual Primary Completion Date :

Apr 9, 2021

Actual Study Completion Date :

Nov 16, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fibrinogen Concentrate (FC) After separation from bypass, patients will receive platelets and FC. The dose of fibrinogen concentrate will be calculated to achieve a level of 300mg/dL after drug administration. If a patient in either arm continues to have post-bypass bleeding, the anesthesiologist will use point of care testing and the transfusion thresholds outlines in the transfusion algorithm to determine appropriate products for transfusion.	Drug: Fibrinogen Concentrate (FC) The dose of fibrinogen concentrate will be calculated to achieve a level of 300mg/dL after drug administration. Other Names: RiaSTAP
Active Comparator: Cryoprecipitate After separation from bypass, patients will receive platelets and cryoprecipitate. Standard transfusion algorithm includes two units of cryoprecipitate, which result in a median post-operative fibrinogen level of 345mg/dL. If a patient in either arm continues to have post-bypass bleeding, the anesthesiologist will use point of care testing and the transfusion thresholds outlines in the transfusion algorithm to determine appropriate products for transfusion.	Drug: Cryoprecipitate Standard transfusion algorithm includes two units of cryoprecipitate, which result in a median post-operative fibrinogen level of 345mg/dL

Arm

Intervention/Treatment

Experimental: Fibrinogen Concentrate (FC)

After separation from bypass, patients will receive platelets and FC. The dose of fibrinogen concentrate will be calculated to achieve a level of 300mg/dL after drug administration. If a patient in either arm continues to have post-bypass bleeding, the anesthesiologist will use point of care testing and the transfusion thresholds outlines in the transfusion algorithm to determine appropriate products for transfusion.

Drug: Fibrinogen Concentrate (FC)

The dose of fibrinogen concentrate will be calculated to achieve a level of 300mg/dL after drug administration.

Other Names:

RiaSTAP

Active Comparator: Cryoprecipitate

After separation from bypass, patients will receive platelets and cryoprecipitate. Standard transfusion algorithm includes two units of cryoprecipitate, which result in a median post-operative fibrinogen level of 345mg/dL. If a patient in either arm continues to have post-bypass bleeding, the anesthesiologist will use point of care testing and the transfusion thresholds outlines in the transfusion algorithm to determine appropriate products for transfusion.

Drug: Cryoprecipitate

Standard transfusion algorithm includes two units of cryoprecipitate, which result in a median post-operative fibrinogen level of 345mg/dL

Outcome Measures

Primary Outcome Measures

Change in clot degradation time [1) within 2 hours of induction of anesthesia prior to CPB 2) after termination of CPB and transfusion of platelets and either cryoprecipitate or fibrinogen (within 1 hour of separation from bypass 3) upon arrival to the ICU 4) 24 hours post-operatively]
Blood samples will be obtained from an arterial line that is required for the planned surgical procedure. They will be centrifuged to yield platelet poor plasma (PPP), stored at -80 degrees Celsius and utilized for the clot analysis. Clot degradation will be determined by degradation kinetic study.

Secondary Outcome Measures

Change in clot strength [1) within 2 hours of induction of anesthesia prior to CPB 2) after termination of CPB and transfusion of platelets and either cryoprecipitate or fibrinogen (within 1 hour of separation from bypass 3) upon arrival to the ICU 4) 24 hours post-operatively]
Blood samples will be obtained from an arterial line that is required for the planned surgical procedure. They will be centrifuged to yield platelet poor plasma (PPP), stored at -80 degrees Celsius and utilized for the clot analysis. Strength will be assessed by rheology and atomic force microscopy (AFM).
Change in clot polymerization kinetic [1) within 2 hours of induction of anesthesia prior to CPB 2) after termination of CPB and transfusion of platelets and either cryoprecipitate or fibrinogen (within 1 hour of separation from bypass 3) upon arrival to the ICU 4) 24 hours post-operatively]
Blood samples will be obtained from an arterial line that is required for the planned surgical procedure. They will be centrifuged to yield platelet poor plasma (PPP), stored at -80 degrees Celsius and utilized for the clot analysis. Polymerization will be determined by thrombin-initiated turbidity/absorbency curves.
Change in clot structure [1) within 2 hours of induction of anesthesia prior to CPB 2) after termination of CPB and transfusion of platelets and either cryoprecipitate or fibrinogen (within 1 hour of separation from bypass 3) upon arrival to the ICU 4) 24 hours post-operatively]
Blood samples will be obtained from an arterial line that is required for the planned surgical procedure. They will be centrifuged to yield platelet poor plasma (PPP), stored at -80 degrees Celsius and utilized for the clot analysis. Fiber alignment will be assessed using fast Fourier transform.
Transfusion requirement intraoperatively [During surgery (up to 6 hours)]
Transfusion requirement intraoperatively will be recorded.
Transfusion requirements within the first 24 hours after surgery [24 hours postoperatively]
Transfusion requirements within the first 24 hours of surgery will be recorded.
Amount of post-operative bleeding [24 hours postoperatively]
Post-operative bleeding will be recorded by 24 hour chest tube output
Mechanical ventilation time [24 hours postoperatively]
Mechanical ventilation time will be recorded.
Length of ICU stay [At discharge from ICU (typically up to 30 days)]
Length of ICU stay will be recorded.
Length of hospital stay [At discharge from hospital (typically up to 30 days)]
Length of hospital stay will be recorded.
Number of adverse events [Within seven days of surgery]
Adverse events within seven days of surgery will be recorded.

Other Outcome Measures

Number of events of postoperative thrombosis [Within the first 24 hours of surgery]
Number of events of postoperative thrombosis will be recorded
Change in fibrinogen plasma level [1) within 2 hours of induction of anesthesia prior to CPB 2) after termination of CPB and transfusion of platelets and either cryoprecipitate or fibrinogen (within 1 hour of separation from bypass 3) upon arrival to the ICU 4) 24 hours post-operatively]
Blood samples will be obtained from an arterial line that is required for the planned surgical procedure. They will be centrifuged to yield platelet poor plasma (PPP), stored at -80 degrees Celsius and utilized for the clot analysis. ELISA will be used to measure coagulation factors at each time point.
Change in thrombin plasma level [1) within 2 hours of induction of anesthesia prior to CPB 2) after termination of CPB and transfusion of platelets and either cryoprecipitate or fibrinogen (within 1 hour of separation from bypass 3) upon arrival to the ICU 4) 24 hours post-operatively]
Blood samples will be obtained from an arterial line that is required for the planned surgical procedure. They will be centrifuged to yield platelet poor plasma (PPP), stored at -80 degrees Celsius and utilized for the clot analysis. ELISA will be used to measure coagulation factors at each time point.
Change in FXIII plasma level [1) within 2 hours of induction of anesthesia prior to CPB 2) after termination of CPB and transfusion of platelets and either cryoprecipitate or fibrinogen (within 1 hour of separation from bypass 3) upon arrival to the ICU 4) 24 hours post-operatively]
Blood samples will be obtained from an arterial line that is required for the planned surgical procedure. They will be centrifuged to yield platelet poor plasma (PPP), stored at -80 degrees Celsius and utilized for the clot analysis. ELISA will be used to measure coagulation factors at each time point.
Change in Willebrand Factor plasma level [1) within 2 hours of induction of anesthesia prior to CPB 2) after termination of CPB and transfusion of platelets and either cryoprecipitate or fibrinogen (within 1 hour of separation from bypass 3) upon arrival to the ICU 4) 24 hours post-operatively]
Blood samples will be obtained from an arterial line that is required for the planned surgical procedure. They will be centrifuged to yield platelet poor plasma (PPP), stored at -80 degrees Celsius and utilized for the clot analysis. ELISA will be used to measure coagulation factors at each time point.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Day to 30 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Full term neonates (36-42 weeks gestational age)
Infants =< 30 days of age
APGAR score of 6 or greater at 5 minutes after delivery
Neonates undergoing elective cardiac surgery requiring CPB at Children's Healthcare of Atlanta
Parents willing to participate and able to understand and sign the provided informed consent

Exclusion Criteria:

Preterm neonates (less than 36 weeks gestation)
Patients undergoing an emergent procedure or surgery not requiring CPB
Patients with personal or family history of a coagulation defect or coagulopathy
Parents unwilling to participate or unable to understand and sign the provided informed consent