Administration of Fibrinogen Concentrate for Refractory Bleeding

Phase 2

Recruiting

• Conditions: Hematological Patients; Bleeding; Platelet Refractoriness
• Interventions: Drug: Fibrinogen Concentrate Human

• Registration Number: NCT05091684
• Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne

Brief Summary

Platelet transfusions are widely employed to prevent or treat bleeding episodes in patients with thrombocytopenia. Patients with bone marrow failure secondary to haematological malignancy and chemotherapy frequently receive prophylactic platelet transfusion when platelet level reaches 10x109.L-1, to avoid spontaneous major bleeding. Due to immune or nonimmune factors, platelet refractoriness may be observed and is defined as a repeated suboptimal response to platelet transfusions with lower-than-expected post-transfusion count increments. The management of patients with alloimmunization is complex and prophylactic platelet support is no longer indicated. Therefore, platelet refractoriness remains a clinically challenging complication.

Detailed Description

To date, no specific therapeutic strategy has been proposed for platelet refractoriness, in cancer patients who are both at high risk of bleeding and thrombosis. Interestingly, fibrinogen is a critical hemostatic protein required for both prevention and treatment of bleeding as it provides a matrix and mesh network essential for clot formation, amplification and strength. Fibrinogen repletion, primarily with the use of fibrinogen concentrates for acquired bleeding, has been reported in clinical settings including surgery, trauma, and obstetrics. However, its use as adjuvant therapy for patients requiring massive transfusion is not yet a widely approved indication, especially in hematological patients. Therefore, the evidence regarding timing, efficacy and safety of fibrinogen administration in massively transfused hematological patients is scarce. This study aims at evaluating whether fibrinogen administration to transfused and refractory patients with on-going bleeding could affect the viscoelastic test of clotting function.

Study Timeline

• Study First Submitted: 2021-10-13
• Study First Submitted QC: 2021-10-13
• Study First Posted: 2021-10-25
• Study Start: 2022-02-10
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-07
• Last Update Posted: 2025-04-09
• Primary Completion: 2025-12
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Patient affiliated to a social security regimen or beneficiary of the same
• Signed written informed consent form
• Confirmed diagnosis of a hematological malignancy and undergoing intensive chemotherapy, autologous stem cell transplantation or allogeneic stem cell transplantation
• Grade ≥ II hemorrhagic symptoms according to WWorld Health Organization classification
• Failure or impossibility to use Human Leucocyte Antigen-matched platelet unit
• Body weight between 38 and 78 Kgs
• Transfusion refractoriness as defined by Corrected count increment ≤ 5 and platelet level < 20.109.L-1

Exclusion Criteria

• Pregnant women
• Patient under guardianship or deprived of his liberty or any condition that may affect the patient's ability to understand and sign the informed consent
• Refusing participation
• Patient presenting non-malignant hematological disease
• Patient with high plasmatic concentration of fibrinogen (>5g/L)
• Patient who received fibrinogen within 20 days before inclusion
• Contra-indication to fibrinogen (fibrinogen concentrate) or any excipient (fibrinogen concentrate)
• Patient with disseminated intravascular coagulopathy
• Patient with thromboembolic history
• Patient who received L-Asparaginase or acquired hypofibrinogenemia following treatment by L-Asparaginase
• Patient with known risk of thrombophilia (deficiency for antithrombin 3, C protein or factor V)
• Patient with anti-thrombotic treatment (anti-platelet or anti-coagulant therapy) at the time of enrolment
• Elevated body temperature ≥ 38.5°C
• Hospital stay for invasive surgery
• Patient with acute myeloid leukemia during the induction phase of chemotherapy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fibrinogen	Fibrinogen Concentrate Human	Patients with refractory thrombocytopenia, following intensive chemotherapy, and presenting grade ≥ 2 hemorrhagic symptoms, will receive adjuvant fibrinogen administration and platelet transfusions.

Primary Outcome Measures

Name	Time	Method
Maximal clot elasticity (viscoelastic test of clotting function)	3 hours	Measurement of viscoelastic test of clotting function represented by the maximal clot elasticity based on the maximal clot firmness from the EXTEM (EXtrinsically activated test) curve, between blood sampling before fibrinogen administration and blood sampling after platelet transfusion

Secondary Outcome Measures

Name	Time	Method
Comparison of viscoelastic test of clotting function before and after treatment using EXTEM (EXtrinsically activated test) and FIBTEM (fibrin clot obtained by platelet inhibition with cytochalasin D) curves (Fibrinogen)	24 hours	Measurement of viscoelastic test of clotting function to determine the contribution of fibrinogen in clotting (before fibrinogen, after fibrinogen, after fibrinogen + platelet transfusion)
Comparison of viscoelastic test of clotting function before and after treatment using EXTEM (EXtrinsically activated test) and FIBTEM (fibrin clot obtained by platelet inhibition with cytochalasin D) curves (platelets)	24 hours	Measurement of viscoelastic test of clotting function and comparison depending on platelet characteristics
Incidence of hemorrhagic and thrombotic events	2 months	Proportions of patients experiencing bleeding and thrombotic events
Incidence of adverse events	2 months	Proportions of patients experiencing adverse events

Trial Locations

Locations (1)

CHU de Saint-Etienne; 🇫🇷 Saint-Étienne, France