Individualized Dose of Fibrinogen Following Cardiopulmonary Bypass (INDOFIB)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Fibrinogen Deficiency in Complex Cardiac Surgery
• Intervention / Treatment: Biological: Blood samples for PK

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Julien LANOISELEE, MD; Phone Number: +33 (0)477120388; Email: julien.lanoiselee@chu-st-etienne.fr

Study Locations

• France
  • Lille, France, 59000
    • CHU de LILLE
    • Contact: Mouhamed MOUSSA, MD, PhD; Phone Number: +33 (0)320445322; Email: mouhamed.moussa@chu-lille.fr
    • Contact: Julien TABAREAU-BEFFY; Phone Number: +33 (0)362943576; Email: julien.tabareau-beffy@chu-lille.fr
  • Saint-Etienne, France, 42000
    • CHU de Saint-Etienne
    • Contact: Julien LANOISELEE, MD; Phone Number: +33 (0)477120388; Email: julien.lanoiselee@chu-st-etienne.fr
    • Contact: Anaèle DESSAGNES; Phone Number: +33 (0)477828556; Email: anaele.dessagnes@chu-st-etienne.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patient admitted for cardiac surgery and receiving fibrinogen administration after weaning from cardiopulmonary bypass

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patient receiving fibrinogen administration after weaning from cardiopulmonary bypass

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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize the sources of variability in plasma fibrinogen levels in response to administration of fibrinogen concentrate after cardiac surgery with cardiopulmonary bypass.	Measurement of blood samples using the Clauss technique	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

Outcome Measure	Measure Description	Time Frame
Characterize the sources of variability in response to fibrinogen concentrate administration as assessed by the ROTEM viscoelastic test.	Measurement of blood samples using the ROTEM viscoelastic test	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.	measurement of blood samples using the Quantra viscoelastic test	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.	Blood loss in ml measured via surgical drains	During surgery (day 0) then at day 1 and day 2.
Study the relationship between different estimators of fibrinogen concentration.	Correlation coefficient between the different estimators of fibrinogen concentration and description using a Bland-Altman plot.	through study completion, an average of 7 days

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Laboratoires LFB
• Investigators: Principal Investigator: Julien LANOISELEE, MD, CHU de Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): November 7, 2028

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: February 13, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: cardiopulmonary bypass; fibrinogen; pharmacokinetic modeling
• Additional Relevant MeSH Terms: Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: 23CH136; ANSM (Other Identifier: 2025-A02921-48)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No