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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03932240
Recruitment Status : Suspended (All subject enrollment/follow up is on hold due to COVID-19 pandemic)
First Posted : April 30, 2019
Last Update Posted : May 1, 2020
Sponsor:
Information provided by (Responsible Party):
Laura A Downey, 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.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : August 13, 2019
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Fibrinogen

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 Name: 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




Primary Outcome Measures :
  1. Change in clot degradation time [ Time Frame: 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 1hour of separation from bypass; 3) 24 hours post-operatively in the ICU ]
    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 -80oC and utilized for the clot analysis. Clot degradation will be determined by degradation kinetic study.


Secondary Outcome Measures :
  1. Change in clot strength [ Time Frame: 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 1hour of separation from bypass; 3) 24 hours post-operatively in the ICU ]
    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 -80oC and utilized for the clot analysis. Strength will be assessed by rheology and atomic force microscopy (AFM).

  2. Change in clot polymerization kinetic [ Time Frame: 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 1hour of separation from bypass; 3) 24 hours post-operatively in the ICU ]
    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 -80oC and utilized for the clot analysis. Polymerization will be determined by thrombin-initiated turbidity/absorbency curves.

  3. Change in in clot structure [ Time Frame: 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 1hour of separation from bypass; 3) 24 hours post-operatively in the ICU ]
    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 -80oC and utilized for the clot analysis. Fiber alignment will be assessed using fast Fourier transform.

  4. Transfusion requirement intraoperatively [ Time Frame: During surgery (up to 6 hours) ]
    Transfusion requirement intraoperatively will be recorded.

  5. Transfusion requirements within the first 24 hours after surgery [ Time Frame: 24 hours postoperatively ]
    Transfusion requirements within the first 24 hours of surgery will be recorded.

  6. Amount of post-operative bleeding [ Time Frame: 24 hours postoperatively ]
    Post-operative bleeding will be recorded by 24 hour chest tube output

  7. Mechanical ventilation time [ Time Frame: 24 hours postoperatively ]
    Mechanical ventilation time will be recorded.

  8. Length of ICU stay. [ Time Frame: Up to 30 days ]
    Length of ICU stay will be recorded.

  9. Length of hospital stay. [ Time Frame: Up to 30 days ]
    Length of hospital stay will be recorded.

  10. Number of adverse events [ Time Frame: Within seven days of surgery ]
    Adverse events within seven days of surgery will be recorded.


Other Outcome Measures:
  1. Number of events of postoperative thrombosis [ Time Frame: Within the first 24 hours of surgery ]
    Number of events of postoperative thrombosis will be recorded

  2. Change in fibrinogen plasma level [ Time Frame: 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 1hour of separation from bypass; 3) 24 hours post-operatively in the ICU ]
    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 -80oC and utilized for the clot analysis. ELISA will be used to measure coagulation factors at each time point.

  3. Change in thrombin plasma level [ Time Frame: 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 1hour of separation from bypass; 3) 24 hours post-operatively in the ICU ]
    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 -80oC and utilized for the clot analysis. ELISA will be used to measure coagulation factors at each time point.lot analysis.

  4. Change in FXIII plasma level [ Time Frame: 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 1hour of separation from bypass; 3) 24 hours post-operatively in the ICU ]
    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 -80oC and utilized for the clot analysis. ELISA will be used to measure coagulation factors at each time point.lot analysis.

  5. Change in Willebrand Factor plasma level [ Time Frame: 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 1hour of separation from bypass; 3) 24 hours post-operatively in the ICU ]
    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 -80oC and utilized for the clot analysis. ELISA will be used to measure coagulation factors at each time point.lot analysis.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 30 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Full term neonates (36-42 weeks gestational age)
  2. Infants =< 30 days of age
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03932240


Locations
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United States, Georgia
Children's Healthcare of Atlanta (CHOA), Egleston
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Investigators
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Principal Investigator: Laura Downey, MD Emory University
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Responsible Party: Laura A Downey, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT03932240    
Other Study ID Numbers: IRB00109310
First Posted: April 30, 2019    Key Record Dates
Last Update Posted: May 1, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices), will be shared.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Beginning 3 months and ending 5 years following article publication.
Access Criteria: Researchers who provide a methodologically sound proposal to achieve aims in the approved protocol. Proposals should be directed to laura.ansley.downey@emory.edu. To gain access, data requestors will need to sign and obtain a data use agreement. The data will be available for five years in the investigator's Emory's data warehouse.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Laura A Downey, Emory University:
Fibrinogen Concentrate
FC
Cryoprecipitate
Transfusion
in vivo
Open-heart surgery
Cardiopulmonary Bypass
Fibrin Network Structure