Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
180
Countries
5
Sites
12
Bleeding in patients undergoing complex cardiac surgery involving Cardiopulmonary bypass
The primary objective of the study is to evaluate the efficacy of FGTW in combination with Standard of care versus Placebo in combination with Standard of care in reducing the need for allogeneic transfusions during the first 24 hours after IMP administration in complex cardiac surgery patients.
Key facts
- Sponsor
- LFB-Biotechnologies
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 29 Nov 2022 → ongoing
- Decision date (initial)
- 2025-02-27
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Laboratoire français du Fractionnement et des Biotechnologies (LFB BIOTECHNOLOGIES)
External identifiers
- EU CT number
- 2024-512388-29-00
- EudraCT number
- 2022-001759-17
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
The primary objective of the study is to evaluate the efficacy of FGTW in combination with Standard of care versus Placebo in combination with Standard of care in reducing the need for allogeneic transfusions during the first 24 hours after IMP administration in complex cardiac surgery patients.
Secondary objectives 1
- - To evaluate the efficacy associated with the use of FGTW versus Placebo in reducing the number of RBC, FFP, and platelet concentrate transfusions between 24 hours after IMP administration and the hospital discharge - To evaluate the efficacy associated with the use of FGTW versus Placebo in reducing the blood drainage volume during 12 hours after IMP administration or skin closure whichever comes last - To evaluate the number of patients with total avoidance of allogeneic transfusions after IMP administration - To evaluate the safety of FGTW - To evaluate the impact of FGTW on mortality and surgical morbidity - To evaluate the duration of hospitalization in both treatment arms - To evaluate the length of stay in ICU in both treatment arms
Conditions and MedDRA coding
Bleeding in patients undergoing complex cardiac surgery involving Cardiopulmonary bypass
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10017501 | Functional disturbances following cardiac surgery | 10022117 |
Study design 4 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Screening "The patient will be considered screened after ICF signature. Once ICF signature, the screening period
can be undertaken. Visit 1 will occur within a maximum of 32 days before surgery (D32 to D-1) to confirm eligibility of the patient."
|
Randomised Controlled | None | Standard of care + FGTW: The dose of FGTW will be based on the values of FIBTEM MCF and patient’s weight and administered intravenously after CPB discontinuation and administration of protamine. The Standard of care for patient blood management in adult cardiac surgery is defined and based on the European Guidelines Standard of care + Placebo: The dummy dose for Placebo will be based on the values of FIBTEM MCF and patient’s weight and administered intravenously after CPB discontinuation and administration of protamine. The Standard of care for patient blood management in adult cardiac surgery is defined and based on the European Guidelines |
|
| 2 | Day of surgery and Randomization Visit 2 will occur on the day of surgery (D1). If FIBTEM MCF is ≤10 mm during the last 20 minutes of CPB and the calculated IMP dose is ≤8 g, patients will be randomized to either Standard of care + FGTW or Standard of care + Placebo using a 1:1 allocation stratified by center and gender. They will receive one administration of up to 6 vials of IMP depending on their FIBTEM MCF results and their weight.
|
Randomised Controlled | Double | [{"id":178471,"code":2,"name":"Investigator"},{"id":178472,"code":4,"name":"Analyst"},{"id":178470,"code":3,"name":"Monitor"},{"id":178469,"code":1,"name":"Subject"}] | Standard of care + FGTW: The dose of FGTW will be based on the values of FIBTEM MCF and patient’s weight and administered intravenously after CPB discontinuation and administration of protamine. The Standard of care for patient blood management in adult cardiac surgery is defined and based on the European Guidelines Standard of care + Placebo: The dummy dose for Placebo will be based on the values of FIBTEM MCF and patient’s weight and administered intravenously after CPB discontinuation and administration of protamine. The Standard of care for patient blood management in adult cardiac surgery is defined and based on the European Guidelines |
| 3 | Postoperative period (Hospital stay) "Visit 3 will occur on the day following surgery (D2).
Visit 4 will occur 2 days after surgery (D3).
Visit 5 will occur 3 days after surgery (D4).
Additional visits may occur daily if the patient remains in hospital.
Hospital discharge will occur at least 3 days after surgery."
|
Randomised Controlled | Double | [{"id":178477,"code":2,"name":"Investigator"},{"id":178475,"code":3,"name":"Monitor"},{"id":178474,"code":4,"name":"Analyst"},{"id":178476,"code":1,"name":"Subject"}] | Standard of care + FGTW: The dose of FGTW will be based on the values of FIBTEM MCF and patient’s weight and administered intravenously after CPB discontinuation and administration of protamine. The Standard of care for patient blood management in adult cardiac surgery is defined and based on the European Guidelines Standard of care + Placebo: The dummy dose for Placebo will be based on the values of FIBTEM MCF and patient’s weight and administered intravenously after CPB discontinuation and administration of protamine. The Standard of care for patient blood management in adult cardiac surgery is defined and based on the European Guidelines |
| 4 | Follow-up EoS visit (either on-site or remotely) will occur at 30 +/- 4 days after the surgery (D30 +/- 4 days).
|
Randomised Controlled | Double | [{"id":178481,"code":4,"name":"Analyst"},{"id":178482,"code":1,"name":"Subject"},{"id":178479,"code":3,"name":"Monitor"},{"id":178480,"code":2,"name":"Investigator"}] | Standard of care + FGTW: The dose of FGTW will be based on the values of FIBTEM MCF and patient’s weight and administered intravenously after CPB discontinuation and administration of protamine. The Standard of care for patient blood management in adult cardiac surgery is defined and based on the European Guidelines Standard of care + Placebo: The dummy dose for Placebo will be based on the values of FIBTEM MCF and patient’s weight and administered intravenously after CPB discontinuation and administration of protamine. The Standard of care for patient blood management in adult cardiac surgery is defined and based on the European Guidelines |
Regulatory references
- Scientific advice from competent authorities
- Paul-Ehrlich-Institut
- Plan to share IPD
- No
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Male or female adult patients ≥18 years
- 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.
- With a FIBTEM MCF ≤10 mm during the last 20 minutes of CPB.
- Patients requiring an IMP dose ≤8 g calculated with the formula based on patient's weight and the value of FIBTEM MCF
- Signed and dated informed consent form (ICF)
- Willingness to comply with all study procedures and availability for the duration of the study
- Covered by healthcare insurance in accordance with local requirements
- 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 21
- Heart transplantation
- Repair of complex congenital abnormalities
- 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
- Known hypersensitivity or other severe reaction to any component of the IMP
- 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)
- Patients unable to stop treatment by vitamin K antagonists 3-5 days before surgery to obtain an international normalized ratio (INR) <1.5
- Patients unable to stop treatment by direct oral anticoagulant at least 48 hours before surgery (except aspirin)
- 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)
- Severe anemia with hemoglobin (Hb) ≤10 g/dL
- 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
- Congenital coagulation deficiencies (von Willebrand disease, factor V Leiden, Protein C deficiency, cryoglobulinemia, antiphospholipid syndrome…)
- Any known thromboembolic disorder
- 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
- Known pregnancy or positive blood pregnancy test for women of childbearing potential and/or breast-feeding women
- 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
- Treatment with fibrinogen concentrate or cryoprecipitate within 32 days prior to randomization
- Previous cardiac surgical procedure within three months before randomization
- Evidence or suspicion of infection (fever >38.5°C and white blood cell count >11/mm3)
- Active endocarditis
- Emergency surgery, patients in cardiogenic shock, or expected mortality within 24 hours of surgery
- Pre-existing thrombocytopenia with platelet count < 150 000/ mm3
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 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.
Secondary endpoints 12
- Blood drainage volume during 12 hours after IMP administration or skin closure whichever comes last
- Percentage of patients with total avoidance of allogeneic transfusions during 24 hours after IMP administration
- 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)
- Number of pre-donated autologous RBC concentrate units, RBC concentrate prepared by cell-saver, colloids, and crystalloids after IMP administration until hospital discharge
- Mortality at 24 hours, 7 days, and 30 days after IMP administration
- Percentage of patients with each surgical morbidity at 24 hours, 7 days, and 30 days after randomization (see Section 9.2.8)
- Percentage of patients with post-surgery stage 1 AKI (with increase in creatinine by >50% from baseline until hospital discharge)
- Percentage of patients with surgical re-exploration due to bleeding during 24 hours after IMP administration
- Percentage of patients with fibrinogen concentration below the LLN from visit 2 to visit 5
- Percentage of patients receiving aPCC/PCCs, rFVIIa, cryoprecipitate or additional FC as rescue therapy within 24 hours after randomization
- Duration of hospitalization
- Length of stay in ICU
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SCP12491473 · ATC
- Active substance
- Human Fibrinogen
- Substance synonyms
- FIBRINOGEN, HUMAN
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 8.00 g gram(s)
- Max total dose
- 8.00 g gram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B02BB01 — FIBRINOGEN, HUMAN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- Route of administration
- INFUSION
- Max daily dose
- 8.00 g gram(s)
- Max total dose
- 8.00 g gram(s)
- Max treatment duration
- 1 Day(s)
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
LFB-Biotechnologies
- Sponsor organisation
- LFB-Biotechnologies
- Address
- Zone Dactivite De Courtaboeuf, 3 Avenue Des Tropiques 3 Avenue Des Tropiques
- City
- Les Ulis
- Postcode
- 91940
- Country
- France
Scientific contact point
- Organisation
- LFB-Biotechnologies
- Contact name
- LFB Medical Information
Public contact point
- Organisation
- LFB-Biotechnologies
- Contact name
- LFB Medical Information
Third parties 4
| Organisation | City, country | Duties |
|---|---|---|
| Icon Clinical Research Limited ORG-100008322
|
Dublin 18, Ireland | On site monitoring, Code 10, Code 12, Other, Code 2, Interactive response technologies (IRT), Laboratory analysis, Code 5, Data management, Code 8, Code 9 |
| Creapharm Bioservices ORG-100048093
|
Bailly-Romainvilliers, France | Other |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | E-data capture |
| Clinigen Clinical Supplies Management ORG-100034422
|
Mont-Saint-Guibert, Belgium | Other |
Locations
5 EU/EEA countries · 12 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Czechia | Ongoing, recruiting | 24 | 3 |
| Germany | Ongoing, recruiting | 16 | 2 |
| Italy | Ongoing, recruiting | 32 | 3 |
| Spain | Ongoing, recruiting | 16 | 2 |
| Sweden | Ongoing, recruiting | 16 | 2 |
| Rest of world
Serbia, United Kingdom, Brazil
|
— | 76 | — |
Investigational sites
Fakultni Nemocnice Hradec Kralove
NA, Sokolska 581, Novy Hradec Kralove, Hradec Kralove
Fakultni Nemocnice Motol A Homolka
NA, V Uvalu 84/1, Motol, Prague
Fakultni Nemocnice Ostrava
NA, 17. Listopadu 1790/5, Poruba, Ostrava
Martin-Luther-Universitaet Halle-Wittenberg
Klinik für Herzchirurgie, Ernst-Grube-Strasse 40, Kroellwitz, Halle (Saale)
Schuechtermann-Schiller'sche Kliniken Bad Rothenfelde GmbH & Co. KG
Department of Anaesthesiology, Ulmenallee 5-11, 49214, Bad Rothenfelde
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
UOC Cardiochirurgia, Via Pietro Albertoni 15, 40138, Bologna
Policlinico San Donato S.p.A.
Unità di Anestesia e Terapia Intensiva Cardiovascolare, Piazza Edmondo Malan 2, 20097, San Donato Milanese
Ospedale San Raffaele S.r.l.
Cardiac, Thoracic, Vascular Anesthesia and Intensive Care Unit, Via Olgettina 60, 20132, Milan
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Czechia | 2025-03-17 | 2025-06-09 | |||
| Germany | 2023-03-29 | 2024-12-10 | |||
| Italy | 2023-07-06 | 2024-03-05 | |||
| Spain | 2022-11-29 | 2024-04-17 | |||
| Sweden | 2023-02-01 | 2024-01-31 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 33 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-512388-29-00_redacted | 9.0 |
| Recruitment arrangements (for publication) | K1_CZ_Recruitment Procedure_Bilingual | 1.0 |
| Recruitment arrangements (for publication) | K1_DE_Recruitment Procedure | 1.1 |
| Recruitment arrangements (for publication) | K1_ES_Recruitment Procedure | 1.0 |
| Recruitment arrangements (for publication) | K1_IT_Recruitment Procedure | 1.0 |
| Recruitment arrangements (for publication) | K1_SE_Recruitment procedure_Swedish | 1.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Data Privacy_Czech | 2.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Main_Czech_redacted | 6.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Scout_Czech_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS-ICF_Main_German_redacted | 6.1 |
| Subject information and informed consent form (for publication) | L1_DE_SIS-ICF_Scout_German_redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Main_Spanish | 6.0 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Scout_Spanish_redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Adults_Italian_redacted | 6.0 |
| Subject information and informed consent form (for publication) | L1_SE_SIS-ICF_Main_Swedish | 6.0 |
| Subject information and informed consent form (for publication) | L1_SE_SIS-ICF_Scout_Swedish_redacted | 3.0 |
| Subject information and informed consent form (for publication) | L2_CZ_Other subject material_Patient Emergency Card_Czech | 1.0 |
| Subject information and informed consent form (for publication) | L2_CZ_Other subject material_SCOUT_Email Communication_Czech | 1.0 |
| Subject information and informed consent form (for publication) | L2_CZ_Other subject material_SCOUT_Study Brochure_Czech | 1.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_FibCLOT | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_FibCLOT_German | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_FIBCLOT_Italian | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_FIBCLOT_Spanish | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_FibCLOT_Swedish | 2 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-512388-29-00 | 2.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-512388-29-00_Czech | 2.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-512388-29-00_Italian | 2.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-512388-29-00_Spanish | 2.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-512388-29-00_Swedish | 2.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2024-512388-29-00_Czech_redacted | 9.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2024-512388-29-00_Italian_redacted | 9.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2024-512388-29-00_redacted | 9.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2024-512388-29-00_Spanish_redacted | 9.0 |
Application history
11 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-04-19 | Germany | Acceptable 2024-05-10
|
2024-05-10 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-08-08 | Germany | Acceptable 2024-10-14
|
2024-10-17 |
| 3 | SUBSEQUENT ADDITION OF MSC | APP-3 | 2024-11-20 | 2025-02-27 | ||
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-11-25 | Acceptable | 2025-01-13 | |
| 5 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-11-26 | Germany | Acceptable | 2024-12-10 |
| 6 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-01-27 | Acceptable | 2025-03-14 | |
| 7 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-06-19 | Germany | Acceptable 2025-09-11
|
2025-09-11 |
| 8 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-10-01 | Acceptable 2025-09-11
|
2025-10-01 | |
| 9 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-10-14 | Acceptable 2025-09-11
|
2025-10-14 | |
| 10 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2026-02-05 | Acceptable 2025-09-11
|
2026-02-05 | |
| 11 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2026-03-26 | Germany | Acceptable 2025-09-11
|
2026-03-26 |