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

NCT03932240 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: IRB00109310
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemostasis

Keywords

Fibrinogen Concentrate; FC; Cryoprecipitate; Transfusion; in vivo; Open-heart surgery; Cardiopulmonary Bypass; Fibrin Network Structure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Clot Strength

  From induction of anesthesia to 24 hours postoperatively

• Clot Polymerization Kinetic

  From induction of anesthesia to 24 hours postoperatively

• Fibrin Fiber Alignment

  From induction of anesthesia to 24 hours postoperatively

• Interoperative Transfusion Requirement

  During surgery (up to 6 hours)

• Transfusion Requirements Within the First 24 Hours After Surgery

  24 hours postoperatively

Other Outcomes (5)

• Number of Events of Postoperative Thrombosis

  Within the first 24 hours of surgery

• Fibrinogen Plasma Level

  From induction of anesthesia to 24 hours postoperatively

• Thrombin Plasma Level

  From induction of anesthesia to 24 hours postoperatively

Study Arms (2)

Fibrinogen Concentrate (FC)

EXPERIMENTAL

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)

Cryoprecipitate

ACTIVE COMPARATOR

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.

Drug: Cryoprecipitate

Interventions

Fibrinogen Concentrate (FC) DRUG

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

Also known as: RiaSTAP

Fibrinogen Concentrate (FC)

Cryoprecipitate DRUG

The standard transfusion algorithm includes two units of cryoprecipitate, which result in a median post-operative fibrinogen level of 286mg/dL.

Cryoprecipitate

Eligibility Criteria

• Age: 1 Day - 30 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Children's Healthcare of Atlanta (CHOA), Egleston

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Downey LA, Moiseiwitsch N, Nellenbach K, Xiang Y, Brown AC, Guzzetta NA. Effect of In Vivo Administration of Fibrinogen Concentrate Versus Cryoprecipitate on Ex Vivo Clot Degradation in Neonates Undergoing Cardiac Surgery. Anesth Analg. 2025 Aug 1;141(2):240-251. doi: 10.1213/ANE.0000000000007123. Epub 2024 Aug 8.

  PMID: 39116012 DERIVED

MeSH Terms

Interventions

Fibrinogen; cryoprecipitate coagulum

Intervention Hierarchy (Ancestors)

Acute-Phase Proteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Blood Coagulation Factors; Protein Precursors; Biological Factors

Results Point of Contact

• Title: Laura Downey, MD
• Organization: Emory University

laura.ansley.downey@emory.edu

404-785-6670

Study Officials

• Laura Downey, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 3, 2019
• First Posted: April 30, 2019
• Study Start: August 13, 2019
• Primary Completion: April 9, 2021
• Study Completion: November 16, 2021
• Last Updated: February 20, 2024
• Results First Posted: March 20, 2023

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

US (1)