Albumin vs. Plasma for PEdiAtric pRiming Trial

Study Overview
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Brief Summary
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This is a randomized controlled trial that compares two different priming composition (albumin vs. fresh frozen plasma) for extracorporeal circulation of pediatric patients under 10 kg of weight. The two approaches are both employed at the moment but there is actually no evidence on the superiority of one over the other. This study is aimed to test the hypothesis that Albumin is superior to fresh frozen plasma in terms of minor bleeding and transfusional requirements.

Detailed Description
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Extracorporeal circulation (ECC) in neonates and infants undergoing cardiac surgery for the correction or palliation of cardiac defects is characterized by temperature variation, activation of coagulation and inflammatory cascades, hemodilution. An excessive dilution of circulating mass determines a variation in colloid-oncotic pressure (COP) that, together with hydrostatic pressure, induces liquids exchange between interstitial space and plasma. COP variation together with inflammatory response due to extracorporeal circulation and temperature variation is the main determinant of interstitial and pulmonary edema occurrence. Intravascular albumin is responsible for 80% for the COP. Golab et al. randomized a population of neonates and infants undergoing to pediatric cardiac surgery procedures in order to reach two different targets of COP through administration of different albumin amounts. His results didn't show significant differences for primary and secondary endpoints except for postoperative ventilation duration. Trials on adult patients undergoing cardiac surgery haven't showed differences in bleeding when varying colloid solution employed. Albumin is preferred to artificial colloids due to reduced risk of anaphylactic reactions and for its capacity to maintain COP. Hemodilution is associated to a reduction in hematocrit, platelet count, fibrinogen and other coagulation factor concentration. Solutions employed for ECC (Extracorporeal Circulation) circuits priming also contain components that could impair hemostasis. In order to reduce the negative effects on the coagulation, many centers for pediatric surgery employ fresh frozen plasma (FFP) for priming solution. Oliver et al randomized a population of 51 cardiopathic, acyanotic children under 10 kg of weight to receive either albumin or FFP as ECC priming. The authors showed a reduction of postoperative bleeding in the group receiving FFP. No significant differences were detected in postoperative coagulation tests. Other studies with small cohorts weren't able to detect significant differences between the two regimens applied by Oliver and colleagues. Currently the patients receiving blood priming are treated with either FFP or albumin in order to maintain a correct COP. Comparative studies are very limited by small populations and haven't yet provided definitive conclusions about eventual superiority of one regimen over another. This is a randomized controlled trial that compares the employment of 5% Albumin (ALB group) versus Fresh Frozen Plasma (FFP group) for priming as per standard protocol of extracorporeal circulation procedure. No modifications to the normal clinical management of the patient are planned. The primary endpoint is to reduce postoperative bleeding (registered as ml/kg in the first 12 postoperative hours). The secondary endpoints are to reduce transfusional requirements for all the blood products (packed red cells, fresh frozen plasma and platelets registered as ml/kg from the beginning of the extracorporeal circulation for up to 48 hours from the termination of the surgery), ventilation support and hospital stay duration. Safety endpoint is represented by the percentage of thromboembolic complications (stroke, peripheric, pulmonary and mesenteric thromboembolisms). Both the treatments employed in this trial are to be considered standard.

Official Title
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Albumin vs. Plasma for PEdiAtric pRiming Trial

Conditions
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Hemorrhage

Intervention / Treatment
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* Drug: Albumin
* Biological: Fresh Frozen Plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: weight under 10 kg cardiovascular surgery procedure with extracorporeal circulation need for hematic priming solution elective surgery informed consent signed Exclusion Criteria: congenital disorders of coagulation system emergency surgery
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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Albumin<br>5% Albumin to be added to the priming solution composed of concentrated red cells to reach a target of 28-30% hematocrit and albumin to reach the standard volume administered to these patients (400 ml) | Drug: Albumin<br>* Albumin 5% added to blood priming solution<br>* Other names: Human Albumin;|
| Active Comparator: Fresh Frozen Plasma<br>Fresh Frozen Plasma to be added to the priming solution composed of concentrated red cells to reach a target of 28-30% hematocrit and plasma to reach the standard volume administered to these patients (400 ml) | Biological: Fresh Frozen Plasma<br>* Fresh Frozen Plasma added to blood priming solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of postoperative bleeding | Postoperative bleeding in ml/kg, as measured by chest drainage | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of units of blood components transfused | All kind of blood products (packed red cells, fresh frozen plasma, platelet concentrate) transfused from the extracorporeal circulation beginning | 48 hours | 
| Hours on artificial ventilation | Artificial ventilation duration from the ICU admission till extubation | hours until extubation, an average of 72 hours | 
| Days of hospital stay | Hospital stay duration from ICU admission till discharge | days until discharge, an average of 10 days | 
| Thromboembolic complications | All kind of thromboembolic complication (peripheric, pulmonary, mesenteric) from ICU admission till discharge from the hospital | Postoperative hospital stay until discharge, an average of 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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albumin, fresh frozen plasma, extracorporeal circulation, cardiovascular surgery, pediatric population