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Administration of Fibrinogen Concentrate for Refractory Bleeding (FORMAT)

Primary Purpose

Hematological Patients, Bleeding, Platelet Refractoriness

Status
Active
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Fibrinogen Concentrate Human
Sponsored by
Centre Hospitalier Universitaire de Saint Etienne
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematological Patients focused on measuring hematology, intensive chemotherapy, platelet transfusion, thrombocytopenia, fibrinogen

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • CHU de Saint-Etienne

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fibrinogen

Arm Description

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

Outcomes

Primary Outcome Measures

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

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)
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)
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)
Measurement of viscoelastic test of clotting function and comparison depending on platelet characteristics
Incidence of hemorrhagic and thrombotic events
Proportions of patients experiencing bleeding and thrombotic events
Incidence of adverse events
Proportions of patients experiencing adverse events

Full Information

First Posted
October 13, 2021
Last Updated
May 4, 2023
Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
Institut de Cancérologie de la Loire
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1. Study Identification

Unique Protocol Identification Number
NCT05091684
Brief Title
Administration of Fibrinogen Concentrate for Refractory Bleeding
Acronym
FORMAT
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

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 10, 2022 (Actual)
Primary Completion Date
May 31, 2023 (Anticipated)
Study Completion Date
July 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
Institut de Cancérologie de la Loire

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematological Patients, Bleeding, Platelet Refractoriness
Keywords
hematology, intensive chemotherapy, platelet transfusion, thrombocytopenia, fibrinogen

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fibrinogen
Arm Type
Experimental
Arm Description
Patients with refractory thrombocytopenia, following intensive chemotherapy, and presenting grade ≥ 2 hemorrhagic symptoms, will receive adjuvant fibrinogen administration and platelet transfusions.
Intervention Type
Drug
Intervention Name(s)
Fibrinogen Concentrate Human
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximal clot elasticity (viscoelastic test of clotting function)
Description
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
Time Frame
3 hours
Secondary Outcome Measure Information:
Title
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)
Description
Measurement of viscoelastic test of clotting function to determine the contribution of fibrinogen in clotting (before fibrinogen, after fibrinogen, after fibrinogen + platelet transfusion)
Time Frame
24 hours
Title
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)
Description
Measurement of viscoelastic test of clotting function to determine the contribution of platelets in clotting (baseline, after fibrinogen + platelet transfusion)
Time Frame
24 hours
Title
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)
Description
Measurement of viscoelastic test of clotting function and comparison depending on platelet characteristics
Time Frame
24 hours
Title
Incidence of hemorrhagic and thrombotic events
Description
Proportions of patients experiencing bleeding and thrombotic events
Time Frame
2 months
Title
Incidence of adverse events
Description
Proportions of patients experiencing adverse events
Time Frame
2 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emilie Chalayer, MD, PhD
Organizational Affiliation
CHU de Saint-Etienne
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Saint-Etienne
City
Saint-Étienne
ZIP/Postal Code
42055
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Administration of Fibrinogen Concentrate for Refractory Bleeding

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