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

Hemostasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03932240
• Other study ID #: IRB00109310
• Status: Completed
• Phase: Phase 3
• Start date: August 13, 2019
• Est. completion date: November 16, 2021

Study information

• Verified date: January 2024
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: November 16, 2021
• Est. primary completion date: April 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 30 Days

Eligibility

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

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

Related Conditions & MeSH terms

• Hemostasis

Intervention

Drug:
• Fibrinogen Concentrate (FC)
The dose of fibrinogen concentrate will be calculated to achieve a level of 300mg/dL after drug administration.
• Cryoprecipitate
The standard transfusion algorithm includes two units of cryoprecipitate, which result in a median post-operative fibrinogen level of 286mg/dL.

Locations

Country	Name	City	State
United States	Children's Healthcare of Atlanta (CHOA), Egleston	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Events of Postoperative Thrombosis	The number of events of clinically significant postoperative thrombosis that required treatment were obtained from medical records.	Within the first 24 hours of surgery
Other	Fibrinogen Plasma Level	Blood samples were obtained from an arterial line that was required for the planned surgical procedure. The samples were centrifuged to yield platelet poor plasma (PPP), stored at -80 degrees Celsius and utilized for the clot analysis. ELISA was used to measure coagulation factors at each time point. Normal fibrinogen plasma values are between 0.5 to 15 mcg/mL.	From induction of anesthesia to 24 hours postoperatively
Other	Thrombin Plasma Level	Blood samples were obtained from an arterial line that was required for the planned surgical procedure. The samples were centrifuged to yield platelet poor plasma (PPP), stored at -80 degrees Celsius and utilized for the clot analysis. ELISA was used to measure coagulation factors at each time point. The reference range for thrombin plasma level is 0.000313 to 0.02 mcg/mL.	From induction of anesthesia to 24 hours postoperatively
Other	FXIII Plasma Level	Blood samples were obtained from an arterial line that was required for the planned surgical procedure. The samples were centrifuged to yield platelet poor plasma (PPP), stored at -80 degrees Celsius and utilized for the clot analysis. ELISA was used to measure coagulation factors at each time point. The reference range for FXIII plasma level is 0.000469 to 0.03 mcg/mL.	From induction of anesthesia to 24 hours postoperatively
Other	Von Willebrand Factor Plasma Level	Blood samples were obtained from an arterial line that was required for the planned surgical procedure. The samples were centrifuged to yield platelet poor plasma (PPP), stored at -80 degrees Celsius and utilized for the clot analysis. ELISA was used to measure coagulation factors at each time point. Lower values may indicate an increased risk of excessive bleeding.	From induction of anesthesia to 24 hours postoperatively
Primary	Clot Degradation at 24 Hours Post-operatively	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.	From induction of anesthesia to 24 hours postoperatively
Secondary	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).	From induction of anesthesia to 24 hours postoperatively
Secondary	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.	From induction of anesthesia to 24 hours postoperatively
Secondary	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.	From induction of anesthesia to 24 hours postoperatively
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Number of Adverse Events	Adverse events within seven days of surgery were obtained from medical records.	Within seven days of surgery