Effectiveness of Different Fibrinogen Preparations in Restoring Clot Firmness — EDIPORE  

Surgery Clinical Trial

Official title: Effectiveness of Different Fibrinogen Preparations in Restoring Clot Firmness

Status Completed

Clinical Trial 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).

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Bleeding
• Blood Loss, Surgical
• Cardiac Disease
• Heart Diseases
• Hypofibrinogenemia
• Surgery
• Surgical Blood Loss

• NCT number: NCT05780125
• Study type: Interventional
• Source: IRCCS Policlinico S. Donato
• Status: Completed
• Phase: Phase 2
• Start date: March 20, 2023
• Completion date: February 6, 2024