Administration of Fibrinogen Concentrate for Refractory Bleeding

NCT05091684 | Terminated Phase 2 DMC

• 2 other identifiers: 2021-02012021-000990-10
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematological Patients; Bleeding; Platelet Refractoriness

Keywords

hematology; intensive chemotherapy; platelet transfusion; thrombocytopenia; fibrinogen

Outcome Measures

Primary Outcomes (1)

• Maximal clot elasticity (viscoelastic test of clotting function)

  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

  3 hours

Secondary Outcomes (5)

• 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

• 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

• 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

• Incidence of hemorrhagic and thrombotic events

  2 months

• Incidence of adverse events

  2 months

Study Arms (1)

Fibrinogen

EXPERIMENTAL

Patients with refractory thrombocytopenia, following intensive chemotherapy, and presenting grade ≥ 2 hemorrhagic symptoms, will receive adjuvant fibrinogen administration and platelet transfusions.

Drug: Fibrinogen Concentrate Human

Interventions

Fibrinogen Concentrate Human DRUG

Refractory transfused patients who present grade ≥ 2 hemorrhagic symptoms will receive a single injection of fibrinogen concentrate (1.5g) followed by platelet transfusion within 2 hours. Blood sampling will be done at different time points to measure clot viscoelasticity: at baseline, after fibrinogen injection, after platelet transfusion and the day after transfusion or before the next platelet transfusion if \< 24 hours.

Fibrinogen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Institut de Cancérologie de la Loire: collaborator

Study Sites (1)

CHU de Saint-Etienne

Saint-Etienne, 42055, France

Location

MeSH Terms

Conditions

Hemorrhage; Thrombocytopenia

Interventions

Fibrinogen

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Intervention Hierarchy (Ancestors)

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

Study Officials

• Emilie Chalayer, MD, PhD

  CHU de Saint-Etienne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2021
• First Posted: October 25, 2021
• Study Start: February 10, 2022
• Primary Completion: May 25, 2023
• Study Completion: June 27, 2023
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)