Individualized Dose of Fibrinogen Following Cardiopulmonary Bypass

Overview

Heart surgery is essential for many cardiovascular conditions, but it is a major operation with a significant mortality rate of around 4% in Europe. Among the main complications encountered postoperatively, hemorrhage occurs at a rate of around 8.2% for severe bleeding and 1.6% for massive bleeding. Hemorrhagic complications are caused by hemostasis disorders attributable to extracorporeal circulation (ECC). Despite recent advances in material design, ECG activates hemostasis, leading to the consumption of various coagulation factors, including fibrinogen, as well as the absorption of fibrinogen by the various components of the circuit. Postoperative hypofibrinogenemia has multiple causes and is correlated with the risk of bleeding and the need for red blood cell transfusions in cardiac surgery under CPB, and therefore indirectly with mortality related to this procedure. The administration of fibrinogen concentrates is the standard treatment; however, the optimal dose to normalize fibrinogen levels and reduce bleeding is unknown. Good practice recommendations in cardiac surgery suggest administering fibrinogen in cases of bleeding associated with fibrinogen levels below 2 g/L. However, the time required to obtain fibrinogen level results from the laboratory (approximately 1 hour) is not always compatible with the urgency of transfusion needs in these situations. Transfusion optimization strategies have been proposed using viscoelastic tests (ROTEM, Werfen, or Quantra, Stago, for example). The administration of fibrinogen guided by these tests has reduced the need for red blood cell transfusions; however, this strategy increases the cost attributable to fibrinogen because it favors its administration without individualizing the dose to be administered. To date, it is not possible to individualize the dose of fibrinogen to be administered based on baseline fibrinogen levels and kinetics. Developing such an administration strategy would allow for i) faster correction of hypofibrinogenemia and ii) a reduction in associated costs by administering the minimum effective dose.

Interventions

• Biological Blood samples for PK
  Samples will be taken at regular intervals to characterize the kinetics of fibrinogen evolution post-transfusion. Sampling times will be at t = 0 (before transfusion), 10 minutes, H1, H3, H6, H9, H12, D1, and D2 relative to the start of fibrinogen transfusion (measurement of fibrinogen levels and viscoelastic tests), then every two days until the end of hospitalization (measurement of fibrinogen levels only).

Primary outcome measures

• Characterize the sources of variability in plasma fibrinogen levels in response to administration of fibrinogen concentrate after cardiac surgery with cardiopulmonary bypass. [Time frame: During surgery (day 0) (before transfusion then at 10min, 1 hour, 3 hours, 6 hours, 9 hours, 12 hours after transfusion) then at day 1, day 2, day 4 and day 6.]

Secondary outcome measures (4)

• Characterize the sources of variability in response to fibrinogen concentrate administration as assessed by the ROTEM viscoelastic test. [Time frame: During surgery (day 0) (before transfusion then at 10min, 1 hour, 3 hours, 6 hours, 9 hours, 12 hours after transfusion) then at day 1 and day 2.]
• Characterize the sources of variability in response to fibrinogen concentrate administration as assessed by the Quantra viscoelastic test. [Time frame: During surgery (day 0) (before transfusion then at 10min, 1 hour, 3 hours, 6 hours, 9 hours, 12 hours after transfusion) then at day 1 and day 2.]
• Characterize the correlation between fibrinogen exposure and postoperative bleeding after fibrinogen administration. [Time frame: During surgery (day 0) then at day 1 and day 2.]
• Study the relationship between different estimators of fibrinogen concentration. [Time frame: through study completion, an average of 7 days]

Eligibility criteria

Inclusion criteria

• Adult
• Patient undergoing cardiac surgery under cardiopulmonary bypass
• Indication for fibrinogen administration after cardiopulmonary bypass weaning
• Patient affiliated with or entitled to social security coverage
• Patient who has received informed consent about the study

Exclusion criteria

• Administration of fibrinogen in the context of massive transfusion
• Contraindication to the administration of the fibrinogen concentrate under study
• Constitutional afibrinogenemia, constitutional dysfibrinogenemia, or any other constitutional diseases related to hemostasis
• Pregnant women, women in labor, breastfeeding women
• Adults subject to legal protection measures (guardianship or curatorship)
• Patients with preoperative anemia < 6 g/dL
• Patients with a life expectancy < 24 hours
• Patients who do not speak French
• Refusal to participate

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 2 centers

• CHU de Lille — Lille
• CHU de Saint-Etienne — Saint-Etienne

Identifiers

NCT: NCT07425600 · 23CH136 · ANSM

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗