Fibrinogen Concentrate In Children Cardiac Surgery 2

Study Overview
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Brief Summary
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The purporse of this study is evaluate whether fibrinogen concentrate reduces postoperative bleeding in pediatric cardiac surgery with cardiopulmonary by-pass.

Detailed Description
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Cardiac surgery in children may be associated with excessive perioperative bleeding. Perioperative excessive bleeding is associated with need of transfusion with allogeneic blood products such as red blood cells, fresh frozen plasma, platelet pools, and cryoprecipitate. Furthermore, bleeding may result in re-exploration, which is associated with increased morbidity and mortality.Recent studies have shown that patients and children undergoing cardiac surgery with pump often experience a significant drop in their levels and function of fibrinogen, and it would be in part responsible for the bleeding. Fibrinogen concentrate (Haemocomplettan P)may reduce perioperative bleeding, requirements of blood transfusion and clinical outcomes in children undergoing cardiac surgery with pump.

Official Title
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Profilatic Fibrinogen Concentrate Reduces Postoperative Bleeding in Pediatric Cardiac Surgery With Cardiopulmonary Bypass: Randomized Study

Conditions
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C.Surgical Procedure; Cardiac, Blood Coagulation Disorders, Hypofibrinogenemia

Intervention / Treatment
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* Drug: Fibrinogen Concentrate
* Other: control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cardiac surgery with pump Written informed consent Age under 28 days of life or RACHS-1 equal or greater than 3 or reoperation with age under 10 years Exclusion Criteria: Coagulopathy (INR > 1.5) Low platelet count (lower than 100.000) Product or albumin allergy Active endocarditis Blalock-Taussig Heart transplant Anemia (hemoglobin < 10 g/dL) Impossibility to receive blood transfusion Hepatic dysfunction (total bilirubin > 1.5 mg/dL) Known or suspected hypersensitivity to fibrinogen concentrate Thrombophilia or previous thrombosis Participation in another study

Ages Eligible for Study
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Maximum Age: 10 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: fibrinogen concentrate<br>patients randomized to fibrinogen group receive intravenous infusion of drug prepared based on ROTEM measurement of maximum clot firmness (MCF) | Drug: Fibrinogen Concentrate<br>* Fibrinogen Concentrate is to be administered as an intravenous infusion after discontinuation of cardiopulmonary bypass and administration of protamine. Subjects are to be given Fibrinogen Concentrate at an individually determined dose based on FIBTEM MCF and body weight as follows: (15 [mm] - MCF [mm]) * body weight [kg] / 140 [mm*kg/g] = gram fibrinogen to be dosed as Fibrinogen Concentrate. Fibrinogen Concentrate is to be infused over 1 to 2 minutes. After Fibrinogen Concentrate infusion, bleeding treatment will follow the predefined, standardized treatment regimen.<br>|
| Placebo Comparator: control<br>patients randomized to the control group will receive the infusion of 0.9% saline (SF0,9%) prepared based on ROTEM measurement of maximum clot firmness (MCF) | Other: control<br>* 0.9% saline is to be administered as an intravenous infusion after discontinuation of cardiopulmonary bypass and administration of protamine. Patients randomized to the control group will receive the infusion of 0.9% saline (SF0,9%) prepared based on ROTEM measurement of maximum clot firmness (MCF). 0.9% saline is to be infused over 1 to 2 minutes. After 0.9% saline infusion, bleeding treatment will follow the predefined, standardized treatment regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The amount of postoperative bleeding | The amount of blood loss (tube drainage) in the first 6 hours of ICU admission and daily until the seventh day of ICU. Re-exploration is mandatory if the patient presente excessive bleeding not responsive to clinical measures (warming, coagulopathy correction and/or thrombocytopenia correction), associated hemodynamic instability or evidence of cardiac tamponade. | Within 7 days after cardiac surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The amount and type of blood transfusion | The amount and type of intraoperative blood transfusion within the first 6 hours of ICU admission and daily up to the seventh day of ICU. | within 7 days after cardiac surgery | 
| Rate of acute kidney injury | According to pediatric RIFLE, will be measured daily. | within 28 days after cardiac surgery | 
| Rate of cardiac complications | Occurrence of arrhythmias, low cardiac output, cardiogenic shock and the need of postoperative ventricular assistance | within 28 days after cardiac surgery | 
| Rate of neurological complications | Incidence of stroke | within 28 days after cardiac surgery | 
| Rate of infection complications | Infection (surgical wound infection, pneumonia, urinary tract infection and bloodstream infection), sepsis, severe sepsis and septic shock. | within 28 days after cardiac surgery | 
| Correlation between clot firmness (FIBTEM) and plasma fibrinogen | Relationship among the results of FIBTEM-A10 and plasma fibrinogen level will be performed at the same time | After the cardiopulmonary bypass (CPB) weaning and after drug administration during the surgery. | 
| Evaluation of the clot firmness before and after the intervention | Evaluation between FIBTEM-A10 that will be measured after the cardiopulmonary bypass (CPB) weaning and after drug intervention | After the cardiopulmonary bypass (CPB) weaning and after drug administration during the surgery. | 
| Evaluation of plasma fibrinogen before and after the intervention | Evaluation between the fibrinogen level that will be measured after the cardiopulmonary bypass (CPB) weaning, after drug intervention and in the ICU admission. | After the cardiopulmonary bypass (CPB) weaning, after drug administration during the surgery and in ICU admission. | 
| Duration of mechanical ventilation | number of hours in which the patient reiman intubated between the date of surgery and discharge from the ICU | within 28 days after cardiac surgery | 
| Length of vasoactive drugs | number of hours in which the patient will use vasoactive drugs between the date of surgery and discharge from the ICU | within 28 days after cardiac surgery | 
| Length of ICU stay | number of days between the admission and discharge from the ICU. | within 28 days after cardiac surgery | 
| Length of hospital stay | number of days between the date of surgery and hospital discharge. | within 28 days after cardiac surgery | 
| Rate of mortality | Death from all causes occurring up to 28 days after surgery. | within 28 days after cardiac surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac surgical procedures, Fibrinogen, Bleeding