Clinical trial NCT05091684: Administration of Fibrinogen Concentrate for Refractory Bleeding
Official title: Administration of Fibrinogen Concentrate for Refractory Bleeding in Hematological Patients With Intensive Chemotherapy-induced Thrombocytopenia - Analysis Using Viscoelastic Haemostatic Assay (FORMAT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hematological Patients
Bleeding
Platelet Refractoriness
Keywords: hematology
intensive chemotherapy
platelet transfusion
thrombocytopenia
fibrinogen
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Institut de Cancérologie de la Loire
First posted: 2021-10-25
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximal clot elasticity (viscoelastic test of clotting function)
timeFrame: 3 hours
Secondary outcomes:
measure: 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)
timeFrame: 24 hours
measure: 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)
timeFrame: 24 hours
measure: 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)
timeFrame: 24 hours
measure: Incidence of hemorrhagic and thrombotic events
timeFrame: 2 months
measure: Incidence of adverse events
timeFrame: 2 months
Other outcomes:
Locations:
city: Saint-Étienne
country: France
facility: CHU de Saint-Etienne
Study officials:
affiliation: CHU de Saint-Etienne
name: Emilie Chalayer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: