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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Hemostasis

Intervention / Treatment
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* Drug: Fibrinogen Concentrate (FC)
* Drug: Cryoprecipitate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Full term neonates (36-42 weeks gestational age) Infants =< 30 days of age at time of surgery 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

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 30 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fibrinogen Concentrate (FC)<br>Neonates undergoing elective cardiac surgery requiring cardiopulmonary bypass (CPB) who are randomized to receive platelets and FC after separation from bypass. 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)<br>* The dose of fibrinogen concentrate will be calculated to achieve a level of 300mg/dL after drug administration.<br>* Other names: RiaSTAP;|
| Active Comparator: Cryoprecipitate<br>Neonates undergoing elective cardiac surgery requiring cardiopulmonary bypass (CPB) who are randomized to 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<br>* Standard transfusion algorithm includes two units of cryoprecipitate, which result in a median post-operative fibrinogen level of 345mg/dL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clot Degradation | Blood samples were obtained from an arterial line that was required for the planned surgical procedure. Samples were centrifuged to yield platelet poor plasma (PPP), stored at -80 degrees Celsius and utilized for the clot analysis. Clot degradation was determined by degradation kinetic study. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clot Strength | 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). | 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 | 
| Clot Polymerization Kinetic | 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. | 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 | 
| Fibrin Fiber Alignment | Clot structure is assessed by examination of images of clot fibrin fiber alignment. Quantification of clot fiber alignment was achieved through the application of an automated algorithm based on a fast Fourier transform that measures the alignment of the fibers, as well as visual inspection. A reference range has not been established for neonates, however, higher values indicate more dense 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 | 
| Interoperative Transfusion Requirement | Blood product transfusion requirements were obtained from electronic medical records. An increased transfusion requirement indicates increased interoperative bleeding, thus, lower values are preferable. | During surgery (up to 6 hours) | 
| Transfusion Requirements Within the First 24 Hours After Surgery | Transfusion requirements within the first 24 hours of surgery were obtained from electronic medical records. | 24 hours postoperatively | 
| Amount of Post-operative Bleeding | Post-operative bleeding was recorded by 24 hour chest tube output. Higher values indicate greater post-operative bleeding. | Up to 24 hours postoperatively | 
| Mechanical Ventilation Time | Mechanical ventilation time was obtained from medical records. Higher values indicate increased need for mechanical ventilation. | Time of extubation (up to 2 weeks) | 
| Length of ICU Stay | Length of ICU stay was obtained from medical records. A shorter ICU stay indicates a favorable state of health. | At discharge from ICU (typically up to 21 days) | 
| Length of Hospital Stay | Length of hospital stay was obtained from medical records. A shorter hospital stay indicates a favorable state of health. | At discharge from hospital (up to 150 days) | 
| Number of Adverse Events | Adverse events within seven days of surgery were obtained from medical records. | Within seven days of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibrinogen Concentrate, FC, Cryoprecipitate, Transfusion, in vivo, Open-heart surgery, Cardiopulmonary Bypass, Fibrin Network Structure