Effectiveness of Different Fibrinogen Preparations in Restoring Clot Firmness (EDIPORE)

February 26, 2024 updated by: Marco Ranucci, IRCCS Policlinico S. Donato

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).

Study Overview

Detailed Description

The Effectiveness of DIfferent fibrinogen PreparatiOns in Restoring clot firmness (EDIPO RE) is a pragmatic, double-blinded, randomized controlled trial testing the hypothesis that FibCLOT is superior to RiaSTAP in restoring fibrinogen-dependent clot firmness in cardiac surgery acquired hypofibrinogenemia.

A randomization sequence was generated by a computerized system, and then sealed envelopes containing the drug assigned were prepared. The randomization ratio of the treatment arms was 1:1. An unblinded biologist 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.

After protamine administration, if microvascular bleeding was observed or suspected, POC testing, including ROTEM® EXTEM and FIBTEM, was run. If FIBTEM MCF was lower than 10 mm, the patient was randomly allocated to receive a dose of RiaSTAP® or FibCLOT® of 30 mg/kg, approximated to the closest between 2 or 3 grams. If no sign of ongoing bleeding was present, or FIBTEM MCF was 10 mm or higher the patient was considered screen failure and excluded from further observation.

Forty patients were randomized to receive the assigned treatment.

Fibrinogen was administrated intravenously by infusion at a rate of approximately 20 ml/min. Ten minutes after fibrinogen administration a second test was performed with ROTEM® EXTEM and FIBTEM tests to record the change of the parameters due to fibrinogen supplementation. No other hemostatic drugs nor transfusions, outside the study drug, were administered between the first and the second testing. In case of ongoing intra- or postoperative bleeding, after the second testing, all the hemostatic corrections were allowed and guaranteed by our institutional protocol for postoperative bleeding management, which includes the following step-by-step interventions:

  • 30-50 mg of additional protamine for the correction of residual heparin, if the CT at INTEM exceeded 20% of the CT at HEPTEM;
  • Additional fibrinogen concentrate, if FIBTEM MCF < 10 mm or Clauss fibrinogen < 150 mg dL-1;
  • Platelet concentrates if P2Y12 receptor inhibitors were discontinued not later than 7 days, a postoperative ADP test at Multiplate® aggregometry < 12 U, or a postoperative platelet count measured or presumed from preoperative count <100,000 cells/µL;
  • 4-factors prothrombin complex concentrate (PCC, Pronativ, Octapharma, Lachen, Switzerland) 20 IU kg-1 if EXTEM CT > 100 s (after correction of fibrinogen and platelet values) or INR > 1,5.

Preoperative, and perioperative data and details of postoperative outcomes were retrieved from our institutional database and patients' medical charts, including demographics, preoperative risk factors, procedure details, postoperative bleeding and transfusions, intensive care unit (ICU), and hospital stay duration. For the study, the following additional data have been collected: preoperative fibrinogen, platelet count, coagulation parameters (prothrombin time, PT; international normalized ratio, INR; activated partial thromboplastin time, aPTT), post protamine EXTEM CT and MCF and FIBTEM MCF; post-fibrinogen supplementation EXTEM CT and MCF and FIBTEM MCF; fibrinogen, platelet count and coagulation at the ICU arrival.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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;

Exclusion Criteria:

  • 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;
  • participation in another clinical study where an experimental product has been administered within 30 days from the day of the inclusion in the study;
  • whatever clinical condition that, in the opinion of the investigator, makes the patients not suitable to the experimentation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: FibCLOT
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).
30 mg/kg of FibCLOT (rounded up to the nearest 2 or 3 grams) after protamine administration
Other Names:
  • Human Fibrinogen concentrate
Active Comparator: RiaSTAP
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).
30 mg/kg of RiaSTAP (rounded up to the nearest 2 or 3 grams) after protamine administration
Other Names:
  • Human Fibrinogen concentrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
FIBTEM MCF (mm)
Time Frame: Within 10 minutes after protamine administration
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)
Time Frame: Within 10 minutes after protamine administration
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 Frame: Within 10 minutes after protamine administration
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postoperative bleeding
Time Frame: 12 and 24 hours after surgery
Amount of postoperative bleeding measured by the cardiac drainages
12 and 24 hours after surgery
Incidence of moderate/severe bleeding
Time Frame: 12 hours after surgery
Number of cases of moderate or severe bleeding, as defined by the Universal Definition of Perioperative bleeding
12 hours after surgery
Incidence of transfusion
Time Frame: 12 and 24 hours after surgery
Number of cases requiring the transfusion of red blood cells and platelet concentrates
12 and 24 hours after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Marco Ranucci, MD, IRCCS Policlinico S. Donato

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 20, 2023

Primary Completion (Actual)

February 6, 2024

Study Completion (Actual)

February 6, 2024

Study Registration Dates

First Submitted

February 22, 2023

First Submitted That Met QC Criteria

March 9, 2023

First Posted (Actual)

March 22, 2023

Study Record Updates

Last Update Posted (Actual)

February 28, 2024

Last Update Submitted That Met QC Criteria

February 26, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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