FORMAT: Administration of Fibrinogen Concentrate for Refractory Bleeding

Sponsor

Centre Hospitalier Universitaire de Saint Etienne (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05091684

Collaborator

Institut de Cancérologie de la Loire (Other)

Enrollment

Location

Arm

16.6

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hematological Patients Bleeding Platelet Refractoriness	Drug: Fibrinogen Concentrate Human	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Administration of Fibrinogen Concentrate for Refractory Bleeding in Hematological Patients With Intensive Chemotherapy-induced Thrombocytopenia - Analysis Using Viscoelastic Haemostatic Assay (FORMAT)

Anticipated Study Start Date :

Feb 10, 2022

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fibrinogen 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 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.

Arm

Intervention/Treatment

Experimental: Fibrinogen

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

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.

Outcome Measures

Primary Outcome Measures

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

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 to determine the contribution of platelets in clotting (baseline, 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.