NCT03932240

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

Completed Phase 3 Results posted Last updated 20 February 2024

What this trial tests

Phase 3 trial testing Fibrinogen Concentrate (FC) in Hemostasis in 36 participants. Completed in 16 November 2021.

Timeline

13 August 2019

Primary endpoint
9 April 2021

16 November 2021

Quick facts

Lead sponsor	Emory University
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	36
Start date	13 August 2019
Primary completion	9 April 2021
Estimated completion	16 November 2021
Sites	1 location across United States

Drugs / interventions tested

• Fibrinogen Concentrate (FC) — full drug profile →
• Cryoprecipitate — full drug profile →

Conditions studied

• Hemostasis — all drugs for Hemostasis →

Sponsor

Emory University

Who can join

Adults 1 Day to 30 Days, any sex, with Hemostasis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Clot Degradation at 24 Hours Post-operatively Primary · 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

After induction of anesthesia prior to CPB

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.65	0.41 – 1.49
Cryoprecipitate	0.88	0.37 – 1.42

After termination of CPB and transfusion of platelets and either cryoprecipitate or fibrinogen

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.78	0.33 – 0.92
Cryoprecipitate	0.46	0.27 – 1.56

Upon arrival to the ICU

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.65	0.44 – 0.88
Cryoprecipitate	0.55	0.28 – 2.39

24 hours post-operatively

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.92	0.55 – 1.42
Cryoprecipitate	0.76	0.34 – 1.22

Fibrin Fiber Alignment Secondary · 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.

After induction of anesthesia prior to CPB

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.46	0.26 – 0.61
Cryoprecipitate	0.54	0.32 – 0.68

After termination of CPB and transfusion of platelets and either cryoprecipitate or fibrinogen

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.52	0.37 – 0.59
Cryoprecipitate	0.54	0.45 – 0.63

Upon arrival to the ICU

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.41	0.31 – 0.58
Cryoprecipitate	0.44	0.37 – 0.66

24 hours post-operatively

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.37	0.15 – 0.52
Cryoprecipitate	0.38	0.10 – 0.58

Interoperative Transfusion Requirement Secondary · 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.

Group	Value	95% CI
Fibrinogen Concentrate (FC)	27.2	19.0 – 36.9
Cryoprecipitate	41.6	29.2 – 52.4

Amount of Post-operative Bleeding Secondary · Up to 24 hours postoperatively

Post-operative bleeding was recorded by 24 hour chest tube output. Higher values indicate greater post-operative bleeding.

Group	Value	95% CI
Fibrinogen Concentrate (FC)	38.5	32.0 – 70.5
Cryoprecipitate	45.5	31.5 – 69.0

Mechanical Ventilation Time Secondary · Time of extubation (up to 2 weeks)

Mechanical ventilation time was obtained from medical records. Higher values indicate increased need for mechanical ventilation.

Group	Value	95% CI
Fibrinogen Concentrate (FC)	63.3	35.6 – 77.9
Cryoprecipitate	117.2	39.9 – 168.0

Length of ICU Stay Secondary · 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.

Group	Value	95% CI
Fibrinogen Concentrate (FC)	7.0	5.0 – 14.0
Cryoprecipitate	8.5	5.3 – 13.3

Length of Hospital Stay Secondary · 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.

Group	Value	95% CI
Fibrinogen Concentrate (FC)	16.0	10.8 – 47.5
Cryoprecipitate	14.5	9.5 – 29.8

Number of Adverse Events Secondary · Within seven days of surgery

Adverse events within seven days of surgery were obtained from medical records.

Group	Value	95% CI
Fibrinogen Concentrate (FC)	6
Cryoprecipitate	11

Number of Events of Postoperative Thrombosis Secondary · Within the first 24 hours of surgery

The number of events of clinically significant postoperative thrombosis that required treatment were obtained from medical records.

Group	Value	95% CI
Fibrinogen Concentrate (FC)	2
Cryoprecipitate	2

Fibrinogen Plasma Level Secondary · From induction of anesthesia to 24 hours postoperatively

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.

Within 2 hours of induction of anesthesia prior to CPB

Group	Value	95% CI
Fibrinogen Concentrate (FC)	1.39	0.99 – 2.11
Cryoprecipitate	1.09	0.75 – 2.20

After termination of CPB and transfusion of platelets and either cryoprecipitate or fibrinogen

Group	Value	95% CI
Fibrinogen Concentrate (FC)	1.26	0.99 – 1.57
Cryoprecipitate	1.97	1.12 – 2.82

Upon arrival to the ICU

Group	Value	95% CI
Fibrinogen Concentrate (FC)	1.42	1.08 – 2.22
Cryoprecipitate	1.28	1.07 – 1.69

24 hours post-operatively

Group	Value	95% CI
Fibrinogen Concentrate (FC)	1.76	1.49 – 2.11
Cryoprecipitate	1.87	1.43 – 2.27

Thrombin Plasma Level Secondary · From induction of anesthesia to 24 hours postoperatively

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.

Within 2 hours of induction of anesthesia prior to CPB

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.02	0.01 – 0.06
Cryoprecipitate	0.07	0.02 – 0.10

After termination of CPB and transfusion of platelets and either cryoprecipitate or fibrinogen

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.02	0.01 – 0.05
Cryoprecipitate	0.05	0.03 – 0.06

Upon arrival to the ICU

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.03	0.02 – 0.06
Cryoprecipitate	0.05	0.03 – 0.06

24 hours post-operatively

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.02	0.01 – 0.08
Cryoprecipitate	0.06	0.03 – 0.08

FXIII Plasma Level Secondary · From induction of anesthesia to 24 hours postoperatively

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.

Within 2 hours of induction of anesthesia prior to CPB

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.03	0.03 – 0.06
Cryoprecipitate	0.03	0.03 – 0.04

After termination of CPB and transfusion of platelets and either cryoprecipitate or fibrinogen

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.04	0.02 – 0.05
Cryoprecipitate	0.04	0.03 – 0.07

Upon arrival to the ICU

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.04	0.03 – 0.06
Cryoprecipitate	0.05	0.04 – 0.07

24 hours post-operatively

Group	Value	95% CI
Fibrinogen Concentrate (FC)	0.03	0.03 – 0.04
Cryoprecipitate	0.04	0.03 – 0.05

Adverse events — posted to ClinicalTrials.gov

Time frame: Information on serious and non-serious adverse events was collected beginning at the time consent to participate in the study was given through 7 days post-surgery. Mortality was collected until the participant was discharged from the hospital (up to 150 days).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Fibrinogen Concentrate (FC)

Serious: 2/18 (11%)

Deaths: 1/18

Cryoprecipitate

Serious: 9/18 (50%)

Deaths: 1/18

Serious adverse events (5 terms)

Reaction	System	Fibrinogen Concentrate (FC)	Cryoprecipitate
Extracorporeal membrane oxygenation (ECMO) within 24 hours	Surgical and medical procedures	—	—
Chest exploration	Surgical and medical procedures	—	—
Infection	Infections and infestations	—	—
Tamponade	Surgical and medical procedures	—	—
Stroke	Vascular disorders	—	—

Other adverse events (2 terms — click to expand)

Reaction	System	Fibrinogen Concentrate (FC)	Cryoprecipitate
Arrhythmia	Cardiac disorders	—	—
Thrombosis	Vascular disorders	—	—

Most-reported serious reactions: Extracorporeal membrane oxygenation (ECMO) within 24 hours, Chest exploration, Infection, Tamponade, Stroke.

Data from ClinicalTrials.gov NCT03932240 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Effect of In Vivo Administration of Fibrinogen Concentrate Versus Cryoprecipitate on Ex Vivo Clot Degradation in Neonates Undergoing Cardiac Surgery.
   Downey LA, Moiseiwitsch N, Nellenbach K, Xiang Y, et al · · 2025 · PMID 39116012 · DOI 10.1213/ane.0000000000007123