Albumin vs. Plasma for PEdiAtric pRiming Trial (APPEAR)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
MI
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San Donato Milanese, MI, Italy, 20097
- IRCCS San Donato
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Albumin
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)
|
Albumin 5% added to blood priming solution
Other Names:
|
|
Active Comparator: Fresh Frozen Plasma
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)
|
Fresh Frozen Plasma added to blood priming solution
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Volume of postoperative bleeding
Time Frame: 24 hours
|
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
Time Frame: 48 hours
|
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
Time Frame: hours until extubation, an average of 72 hours
|
Artificial ventilation duration from the ICU admission till extubation
|
hours until extubation, an average of 72 hours
|
|
Days of hospital stay
Time Frame: days until discharge, an average of 10 days
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Hospital stay duration from ICU admission till discharge
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days until discharge, an average of 10 days
|
|
Thromboembolic complications
Time Frame: Postoperative hospital stay until discharge, an average of 10 days
|
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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Marco Ranucci, MD, FESC, IRCCS Policlinico S. Donato
Publications and helpful links
General Publications
- Weil MH, Henning RJ, Puri VK. Colloid oncotic pressure: clinical significance. Crit Care Med. 1979 Mar;7(3):113-6. doi: 10.1097/00003246-197903000-00006. No abstract available.
- Golab HD, Scohy TV, de Jong PL, Kissler J, Takkenberg JJ, Bogers AJ. Relevance of colloid oncotic pressure regulation during neonatal and infant cardiopulmonary bypass: a prospective randomized study. Eur J Cardiothorac Surg. 2011 Jun;39(6):886-91. doi: 10.1016/j.ejcts.2010.09.040. Epub 2010 Nov 5.
- Chandler WL. Effects of hemodilution, blood loss, and consumption on hemostatic factor levels during cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2005 Aug;19(4):459-67. doi: 10.1053/j.jvca.2004.11.046.
- Oliver WC Jr, Beynen FM, Nuttall GA, Schroeder DR, Ereth MH, Dearani JA, Puga FJ. Blood loss in infants and children for open heart operations: albumin 5% versus fresh-frozen plasma in the prime. Ann Thorac Surg. 2003 May;75(5):1506-12. doi: 10.1016/s0003-4975(02)04991-3.
- McCall MM, Blackwell MM, Smyre JT, Sistino JJ, Acsell JR, Dorman BH, Bradley SM. Fresh frozen plasma in the pediatric pump prime: a prospective, randomized trial. Ann Thorac Surg. 2004 Mar;77(3):983-7; discussion 987. doi: 10.1016/j.athoracsur.2003.09.030.
- Bianchi P, Cotza M, Beccaris C, Silvetti S, Isgro G, Pome G, Giamberti A, Ranucci M; Surgical and Clinical Outcome REsearch (SCORE) group. Early or late fresh frozen plasma administration in newborns and small infants undergoing cardiac surgery: the APPEAR randomized trial. Br J Anaesth. 2017 May 1;118(5):788-796. doi: 10.1093/bja/aex069.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- APPEAR
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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