Effectiveness of Different Fibrinogen Preparations in Restoring Clot Firmness

NCT05780125 | Completed Phase 2 DMC

• 1 other identifier: EDIPORE
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Fibrinogen concentrate is produced by different manufacturers using different purification technologies. The products available in Italy are three: RiaSTAP (CSL Behring), FIBRYGA (Octapharma), and FibCLOT (LFB). RiaSTAP and FIBRYGA are sold in 1-gram vials, and FibCLOT - in 1.5-gram vials. A recent in vitro study assessed how these products affected the clot firmness measured by the ROTEM FIBTEM maximum clot firmness (MCF) parameter. In vitro conditions, FibCLOT was verified to be the most efficient in increasing clot firmness. The present study is aimed to assess, in a series of patients undergoing cardiac surgery with cardiopulmonary bypass, the hypothesis that the FibCLOT fibrinogen is superior to the RiaSTAP fibrinogen in increasing the FIBTEM MCF parameter in a clinical model of bleeding (postoperative bleeding after complex cardiac surgery).

Conditions

Hypofibrinogenemia; Surgical Blood Loss; Bleeding; Cardiac Disease; Surgery

Keywords

hypofibrinogenemia; cardiac surgery; postoperative bleeding

Outcome Measures

Primary Outcomes (3)

• FIBTEM MCF (mm)

  Fibrinogen contribution to the clot firmness measured by ROTEM device, as maximum clot firmness parameter).

  Within 10 minutes after protamine administration

• FIBTEM CT and CFT (sec)

  Fibrinogen contribution to the clot firmness measured by ROTEM device, as time required for clot formation (CT, clotting time, and CFT, clot formation time).

  Within 10 minutes after protamine administration

• EXTEM CT and CFT (sec)

  Time required for the overall clot formation on the extrinsic pathway of coagulation ( CT, clotting time, and CFT, clot formation time).

  Within 10 minutes after protamine administration

Secondary Outcomes (3)

• Postoperative bleeding

  12 and 24 hours after surgery

• Incidence of moderate/severe bleeding

  12 hours after surgery

• Incidence of transfusion

  12 and 24 hours after surgery

Study Arms (2)

FibCLOT

EXPERIMENTAL

Patients randomized to the FibCLOT arm will receive 30 mg/kg, approximated to the closest between 2 and 3 grams, of FibCLOT (LFB, Puteaux, France).

Drug: FibCLOT

RiaSTAP

ACTIVE COMPARATOR

Patients randomized to the RiaSTAP arm will receive 30 mg/kg, approximated to the closest between 2 and 3 grams, of RiaSTAP (King of Prussia, PA, USA).

Drug: RiaSTAP

Interventions

FibCLOT DRUG

30 mg/kg of FibCLOT (rounded up to the nearest 2 or 3 grams) after protamine administration

Also known as: Human Fibrinogen concentrate

FibCLOT

RiaSTAP DRUG

30 mg/kg of RiaSTAP (rounded up to the nearest 2 or 3 grams) after protamine administration

Also known as: Human Fibrinogen concentrate

RiaSTAP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• elective cardiac surgery with cardiopulmonary bypass;
• complex cardiac surgery (coronary artery bypass graft + valve repair/replacement; double/triple valve repair/replacement; ascendant aorta surgery);
• written consent to participate;

You may not qualify if:

• urgent or emergent cardiac surgery;
• known hypersensitivity to the active principle or to one of the excipients of the study drugs;
• coagulation disorders, known or presumable from anamnesis;
• known hepatopathy;
• known risk of thrombosis or disseminated intravascular coagulation;
• whatever clinical condition that, in the opinion of the investigator, makes the patients not suitable to the experimentation.

Sponsors & Collaborators

• IRCCS Policlinico S. Donato: lead

Study Sites (1)

IRCCS Policlinico San Donato

San Donato Milanese, MI, 20097, Italy

Location

Related Publications (6)

• Ranucci M, Baryshnikova E. Fibrinogen supplementation after cardiac surgery: insights from the Zero-Plasma trial (ZEPLAST). Br J Anaesth. 2016 May;116(5):618-23. doi: 10.1093/bja/aev539. Epub 2016 Feb 17.

  PMID: 26893405 BACKGROUND

• Stolt H, Shams Hakimi C, Singh S, Jeppsson A, Karlsson M. A comparison of the in vitro effects of three fibrinogen concentrates on clot strength in blood samples from cardiac surgery patients. Acta Anaesthesiol Scand. 2021 Nov;65(10):1439-1446. doi: 10.1111/aas.13967. Epub 2021 Sep 1.

  PMID: 34368944 BACKGROUND

• Scolletta S, Simioni P, Campagnolo V, Celiento M, Fontanari P, Guadagnucci A, Guarracino F, Haxhiademi D, Paniccia R, Simeone F, Ranucci M; Granducato Research Group. Patient blood management in cardiac surgery: The "Granducato algorithm". Int J Cardiol. 2019 Aug 15;289:37-42. doi: 10.1016/j.ijcard.2019.01.025. Epub 2019 Jan 11.

  PMID: 30711263 BACKGROUND

• Tibi P, McClure RS, Huang J, Baker RA, Fitzgerald D, Mazer CD, Stone M, Chu D, Stammers AH, Dickinson T, Shore-Lesserson L, Ferraris V, Firestone S, Kissoon K, Moffatt-Bruce S. STS/SCA/AmSECT/SABM Update to the Clinical Practice Guidelines on Patient Blood Management. J Cardiothorac Vasc Anesth. 2021 Sep;35(9):2569-2591. doi: 10.1053/j.jvca.2021.03.011. Epub 2021 Jun 30. No abstract available.

  PMID: 34217578 BACKGROUND

• Dyke C, Aronson S, Dietrich W, Hofmann A, Karkouti K, Levi M, Murphy GJ, Sellke FW, Shore-Lesserson L, von Heymann C, Ranucci M. Universal definition of perioperative bleeding in adult cardiac surgery. J Thorac Cardiovasc Surg. 2014 May;147(5):1458-1463.e1. doi: 10.1016/j.jtcvs.2013.10.070. Epub 2013 Dec 9.

  PMID: 24332097 BACKGROUND

• Baryshnikova E, Aloisio T, Di Dedda U, Anguissola M, Barbaria A, Caravella G, Ranucci M. A Randomized Controlled Trial Comparing Effectiveness of Different Fibrinogen Preparations in Restoring Clot Firmness. Anesth Analg. 2025 Apr 1;140(4):966-973. doi: 10.1213/ANE.0000000000007201. Epub 2024 Oct 9.

  PMID: 39383100 DERIVED

MeSH Terms

Conditions

Afibrinogenemia; Blood Loss, Surgical; Hemorrhage; Heart Diseases; Postoperative Hemorrhage

Interventions

Fibrinogen

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraoperative Complications; Cardiovascular Diseases; Postoperative Complications

Intervention Hierarchy (Ancestors)

Acute-Phase Proteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Blood Coagulation Factors; Protein Precursors; Biological Factors

Study Officials

• Marco Ranucci, MD

  IRCCS Policlinico S. Donato

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A computerized system generated a randomization sequence, and then sealed envelopes containing the drug assigned was prepared. The randomization ratio of the treatment arms was 1:1. An unblinded biologist (E.B.) was in charge of running the ROTEM® tests, randomization, drug preparation, and masking, and its delivery to the operating room. The attending anesthesiologist, the surgical staff, and the medical staff in the ICU and ward were blinded.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Cardiovascular Anesthesia and Intensive Care Department

Model Details: Prospective, double-blind, randomized

Study Record Dates

• First Submitted: February 22, 2023
• First Posted: March 22, 2023
• Study Start: March 20, 2023
• Primary Completion: February 6, 2024
• Study Completion: February 6, 2024
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)