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

Phase 3

Completed

• Conditions: Hemostasis
• Interventions: Drug: Fibrinogen Concentrate (FC); Drug: Cryoprecipitate

• Registration Number: NCT03932240
• Lead Sponsor: Emory University

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.

Detailed Description

This study is a prospective, randomized control trial comparing two different sources of fibrinogen on clot kinetics (degradation and structure) 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-04-03
• Study First Submitted QC: 2019-04-28
• Study First Posted: 2019-04-30
• Study Start: 2019-08-13
• Primary Completion: 2021-04-09
• Study Completion: 2021-11-16
• Disposition First Submitted: 2022-03-14
• Results First Submitted: 2022-09-30
• Results First Submitted QC: 2023-02-21
• Results First Posted: 2023-03-20
• Disposition First Posted: 2023-03-20
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-30
• Last Update Posted: 2024-02-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

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

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fibrinogen Concentrate (FC)	Fibrinogen Concentrate (FC)	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.
Cryoprecipitate	Cryoprecipitate	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 286mg/dL (based on findings by Downey et al., published in Anesthesia and Analgesia in 2020). 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.

Primary Outcome Measures

Name	Time	Method
Clot Degradation at 24 Hours Post-operatively	From induction of anesthesia to 24 hours postoperatively	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. Blood samples were collected at four time points:1) baseline sample within 24 hours of surgery and after 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. The primary outcome is to examine differences in clot degradation between study arms at 24 hours post-surgery.

Secondary Outcome Measures

Name	Time	Method
Interoperative Transfusion Requirement	During surgery (up to 6 hours)	Blood product transfusion requirements were obtained from electronic medical records. An increased transfusion requirement indicates increased interoperative bleeding, thus, lower values are preferable.
Length of Hospital Stay	At discharge from hospital (up to 150 days)	Length of hospital stay was obtained from medical records. A shorter hospital stay indicates a favorable state of health.
Amount of Post-operative Bleeding	Up to 24 hours postoperatively	Post-operative bleeding was recorded by 24 hour chest tube output. Higher values indicate greater post-operative bleeding.
Clot Polymerization Kinetic	From induction of anesthesia to 24 hours postoperatively	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.
Clot Strength	From induction of anesthesia to 24 hours postoperatively	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).
Transfusion Requirements Within the First 24 Hours After Surgery	24 hours postoperatively	Transfusion requirements within the first 24 hours of surgery were obtained from electronic medical records.
Mechanical Ventilation Time	Time of extubation (up to 2 weeks)	Mechanical ventilation time was obtained from medical records. Higher values indicate increased need for mechanical ventilation.
Length of ICU Stay	At discharge from ICU (typically up to 21 days)	Length of ICU stay was obtained from medical records. A shorter ICU stay indicates a favorable state of health.
Number of Adverse Events	Within seven days of surgery	Adverse events within seven days of surgery were obtained from medical records.
Fibrin Fiber Alignment	From induction of anesthesia to 24 hours postoperatively	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.

Trial Locations

Locations (1)

Children's Healthcare of Atlanta (CHOA), Egleston; 🇺🇸 Atlanta, Georgia, United States