Administration of Fibrinogen Concentrate for Refractory Bleeding (FORMAT)

Centre Hospitalier Universitaire de Saint Etienne

Status and phase: Terminated; Phase 2

Conditions: Platelet Refractoriness; Hematological Patients; Bleeding

Treatments: Drug: Fibrinogen Concentrate Human

Study type: Interventional

Funder types: Other

Identifiers

NCT05091684

2021-0201

2021-000990-10 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1 patient

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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1 participants in 1 patient group

Fibrinogen

Experimental group

Description:

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

Treatment:

Drug: Fibrinogen Concentrate Human