HUMAN FIBRINOGEN for Bleeding in patients undergoing complex cardiac surgery involving cardiopulmonary bypass

Stratification factors

• center
• gender

Inclusion criteria

• {"criterion_text":"- Male or female adult patients ≥18 years\n- Patients undergoing a planned complex cardiac surgery procedure involving CPB, including reoperation and/or complex surgical procedures. Complex surgical procedures are defined as any procedure other than first time isolated coronary artery bypass grafting (CABG), single valve repair/replacement and repair of atrial septal defect (ASD). This criterion represents the main eligibility criterion and so used in the definition of the full analysis set.\n- With a FIBTEM MCF ≤10 mm during the last 20 minutes of CPB.\n- Patients requiring an IMP dose ≤8 g calculated with the formula based on patient's weight and the value of FIBTEM MCF\n- Signed and dated informed consent form (ICF)\n- Willingness to comply with all study procedures and availability for the duration of the study\n- Covered by healthcare insurance in accordance with local requirements\n- FIBTEM MCF ≤14 mm during the screening period prior to the surgery. FIBTEM MCF is the recommended test, for consistency with end of CPB FIBTEM MCF. Fibrinogen concentration (Clauss method) may be substituted, with fibrinogen level ≤3 g/L. Note: the objective of this criterion is to allow to screen fail patients unlikely to meet inclusion criterion #3 prior to surgery rather than at the end of CPB and reduce the patient’s and site’s constraints of continuing the screening process throughout surgery. However, a patient with a preoperative FIBTEM MCF > 14 mm (or plasma fibrinogen > 3 g/L) can, under exceptional circumstances, continue to be screened until FIBTEM MCF measurement during the last 20 minutes of CPB, if, in the investigator’s judgement, the patient is considered at high risk of clinically significant bleeding (e.g., complex multiple procedures or an expected very long duration - several hours - of CPB)."}

Exclusion criteria

• {"criterion_text":"- Heart transplantation\n- Excessive hemodilution with hematocrit (Ht) <22% in men and women at the time of taking sample for FIBTEM MCF during the last 20 minutes of CPB\n- Congenital coagulation deficiencies (von Willebrand disease, factor V Leiden, Protein C deficiency, cryoglobulinemia, antiphospholipid syndrome…)\n- Any known thromboembolic disorder\n- Female of reproductive potential not using effective contraception (condoms; occlusive caps with spermicide; injectable, patch, or combined oral estro-progestative or progestative contraceptives; depot intramuscular medroxyprogesterone; or subcutaneous implants of progestative contraceptive implants) for at least one month prior to screening\n- Known pregnancy or positive blood pregnancy test for women of childbearing potential and/or breast-feeding women\n- Participation in another clinical study involving an investigational medicinal product within 30 days prior to screening or or 5 half-lives of this investigational medicinal product, whichever is longer, or concomitantly with this study\n- Treatment with fibrinogen concentrate or cryoprecipitate within 32 days prior to randomization\n- Previous cardiac surgical procedure within three months before randomization\n- Evidence or suspicion of infection (fever >38.5°C and white blood cell count >11/mm3)\n- Active endocarditis\n- Repair of complex congenital abnormalities\n- Emergency surgery, patients in cardiogenic shock, or expected mortality within 24 hours of surgery\n- Pre-existing thrombocytopenia with platelet count < 150 000/ mm3\n- Any known pulmonary, hepatic, or renal disease or any other major concomitant significant medical condition that might interfere with treatment evaluation according to the Investigator's judgment\n- Known hypersensitivity or other severe reaction to any component of the IMP\n- Patients at high risk of thrombotic events unable to stop prophylactic low-molecular-weight heparin (LMWH) 12 hours and fondaparinux 24 hours before surgery (longer interval in case of impaired renal function)\n- Patients unable to stop treatment by vitamin K antagonists 3-5 days before surgery to obtain an international normalized ratio (INR) <1.5\n- Patients unable to stop treatment by direct oral anticoagulant at least 48 hours before surgery (except aspirin)\n- 8. Patients unable to stop treatment by P2Y12 inhibitors before surgery (discontinuation duration before surgery: ticagrelor 3 days, clopidogrel 5 days, and prasugrel 7 days)\n- Severe anemia with hemoglobin (Hb) ≤10 g/dL"}

Primary endpoints

• {"endpoint_text":"- The primary efficacy endpoint is the number of units of allogeneic blood products (RBC plus FFP plus platelet concentrate) given to patients between IMP administration and 24 hours thereafter.","definition_or_measurement_approach":"Number of units of allogeneic blood products (RBC + FFP + platelet concentrate) administered to patients between IMP administration and 24 hours after IMP administration."}

Secondary endpoints

• {"endpoint_text":"- Blood drainage volume during 12 hours after IMP administration or skin closure whichever comes last\n- Percentage of patients with total avoidance of allogeneic transfusions during 24 hours after IMP administration\n- Number of transfusion units infused between 24 hours after randomization and the hospital discharge for each class of allogeneic blood product (RBC, FFP, and platelet concentrate)\n- Number of pre-donated autologous RBC concentrate units, RBC concentrate prepared by cell-saver, colloids, and crystalloids after IMP administration until hospital discharge\n- Mortality at 24 hours, 7 days, and 30 days after IMP administration\n- Percentage of patients with each surgical morbidity at 24 hours, 7 days, and 30 days after randomization (see Section 9.2.8)\n- Percentage of patients with post-surgery stage 1 AKI (with increase in creatinine by >50% from baseline until hospital discharge)\n- Percentage of patients with surgical re-exploration due to bleeding during 24 hours after IMP administration\n- Percentage of patients with fibrinogen concentration below the LLN from visit 2 to visit 5\n- Percentage of patients receiving aPCC/PCCs, rFVIIa, cryoprecipitate or additional FC as rescue therapy within 24 hours after randomization\n- Duration of hospitalization\n- Length of stay in ICU","definition_or_measurement_approach":"Each endpoint is measured as described in the endpoint text (e.g., blood drainage volume measured during 12 hours after IMP administration or skin closure; avoidance of allogeneic transfusion measured as percentage of patients during 24 hours after IMP administration; mortality measured at specified timepoints)."}

Italy

Earliest CTIS Part Ii Submission Date

16-04-2024

Latest Decision Or Authorization Date

15-05-2024

Processing Time Days

29

Number Of Sites

3

Number Of Participants

32

Germany

Earliest CTIS Part Ii Submission Date

16-04-2024

Latest Decision Or Authorization Date

15-05-2024

Processing Time Days

29

Number Of Sites

2

Number Of Participants

16

Sweden

Earliest CTIS Part Ii Submission Date

16-04-2024

Latest Decision Or Authorization Date

13-05-2024

Processing Time Days

27

Number Of Sites

2

Number Of Participants

16

Spain

Earliest CTIS Part Ii Submission Date

16-04-2024

Latest Decision Or Authorization Date

10-05-2024

Processing Time Days

24

Number Of Sites

2

Number Of Participants

16

Czechia

Earliest CTIS Part Ii Submission Date

28-01-2025

Latest Decision Or Authorization Date

27-02-2025

Processing Time Days

30

Number Of Sites

3

Number Of Participants

24

Primary sponsor

Full Name

LFB-Biotechnologies

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Sponsor duties codes: 1, 10, 12, 15 (IDMC management/oversight), 2, 3, 4, 5, 6, 8, 9

Third parties

• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Sponsor duties codes: 1, 10, 12, 15 (IDMC management/oversight), 2, 3, 4, 5, 6, 8, 9","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Creapharm Bioservices","duties_or_roles":"Supply and logistics of laboratory kits, samples storage (sponsor duties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Sponsor duties code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"Long Term sample storage (sponsor duties code 15)","organisation_type":"Pharmaceutical company"}