Effectiveness of Different Fibrinogen Preparations in Restoring Clot Firmness

Study Overview
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Brief Summary
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Fibrinogen concentrate is produced by different manufacturers using different purification technologies. The products available in Italy are three: RIASTAP (CSL Behring), FIBRYGA (Octapharma), and FIBRICLOTTE (LFB). RIASTAP and FIBRYGA are sold in 1-gram vials, and FIBRICLOTTE - in 1.5 grams 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, FIBRICLOTTE 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 FIBRICLOTTE 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).

Official Title
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Effectiveness of Different Fibrinogen Preparations in Restoring Clot Firmness

Conditions
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Surgery, Hypofibrinogenemia, Surgical Blood Loss, Bleeding, Cardiac Disease

Intervention / Treatment
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* Drug: FIBRICLOTTE
* Drug: RiaSTAP


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FIBRICLOTTE<br> | Drug: FIBRICLOTTE<br>* 30 mg/kg of FIBRICLOTTE (rounded up to the nearest 2 or 3 grams) after protamine administration<br>|
| Active Comparator: RIASTAP<br> | Drug: RiaSTAP<br>* 30 mg/kg of RIASTAP (rounded up to the nearest 2 or 3 grams) after protamine administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypofibrinogenemia, cardiac surgery, postoperative bleeding