Fibrinogen Concentrate vs Cryoprecipitate

Study Overview
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Brief Summary
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One of the most common hemostatic derangements in pediatric open- heart surgery is an acute acquired hypofibrinogenemia. This compromises fibrin clot generation and platelet aggregation, resulting in increased bleeding and allogenic blood transfusions. Currently, fresh frozen plasma and cryoprecipitate are used to supplement fibrinogen in pediatric cardiac patients. We propose that replacing cryoprecipitate with fibrinogen concentrate will be as effective in treating post-CPB bleeding and will decrease total blood product exposure when used as part of a blood transfusion algorithm. We plan to include all patients undergoing cardiac surgery on CPB less than 12 months and a fibrinogen level <250mg/dL while on bypass. We hope to demonstrate that fibrinogen concentrate is at least as effective as the standard of care in the management of peri- operative bleeding in neonatal patients undergoing cardiopulmonary bypass. If we are able to demonstrate that fibrinogen is at least as effective as the standard of care, then we would plan a multi-center trial to demonstrate the safety and efficacy of this medication. If we are able to demonstrate that fibrinogen concentrate is effective, fibrinogen concentrate could replace allogenic products and potentially decrease transfusion related morbidity in mortality in this population.

Detailed Description
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Patients under 12 months of age requiring cardiopulmonary bypass surgery will be approached for the study. Patients with a pre- existing coagulopathy, including unexplained bleeding or history of clotting, will be excluded. Prior to the study beginning, patients will be randomized to our standard transfusion algorithm with cryoprecipitate or fibrinogen concentrate. As is standard of care, laboratory tests will be sent at standard times points after the induction of anesthesia, after initiation of bypass, after separation from bypass and administration of protamine, and transfusion of either fibrinogen concentrate or cryoprecipitate on arrival to the ICU. These laboratory tests include hematocrit, arterial blood gas, chemistry, thromboelastogram (TEG) and fibrinogen. Additional laboratory tests will be sent as indicated by the clinical scenario to determine transfusion requirements. For patients enrolled in the study, we will standardize the anesthetic management, cardiopulmonary bypass protocol, and transfusion thresholds in the operating room and ICU. We will collect demographic data, intraop and post-op laboratory values, bypass times, intraop and post op transfusion data, chest tube output, adverse events, and length of ventilation, ICU stay and hospital stay. For patients randomized to the study arm (fibrinogen concentrate), the fibrinogen level measured on bypass will be used to calculate the appropriate dose of fibrinogen concentrate to achieve a level of 300mg/dL after separation from bypass. Fibrinogen concentrate will replace cryoprecipitate in our post-operative transfusion algorithm. If the patient has continued bleeding based on laboratory values and clinical situation, the patient will be given cryoprecipitate as a rescue measure. Patients not on the study protocol will receive our normal transfusion algorithm.

Official Title
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Repurposing of Fibrinogen Concentrate as a Cost-Effective and Safe Hemostatic Agent in Infants Undergoing Cardiac Surgery on Cardiopulmonary Bypass

Conditions
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Congenital Heart Disease

Intervention / Treatment
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* Biological: Fibrinogen Concentrate
* Biological: Cryoprecipitate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neonates of at least 32 weeks of gestational age and infants up to 12 months of age with the diagnosis of congenital heart disease, requiring open heart surgery with cardiopulmonary bypass Exclusion Criteria: Pre-existing coagulopathy, including unexplained bleeding or history of clotting

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 12 Months

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cryoprecipitate Arm<br>Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group | Biological: Cryoprecipitate<br>* Subject will be administered Cryoprecipitate to control bleeding after open heart surgery when randomized to Cryoprecipitate group<br>|
| Active Comparator: Fibrinogen Concentrate Arm<br>Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group | Biological: Fibrinogen Concentrate<br>* Subject will be administered Fibrinogen Concentrate to control bleeding after open heart surgery when randomized to Fibrinogen Concentrate group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Units of Intraoperative Allogenic Donor Transfusions (ADT) Administered During Procedure Through ICU Arrival. | For our study, 1 donor exposure = 1 unit of blood product transfusion. A blood product includes red blood cells, fresh frozen plasma, cryoprecipitate, and platelets. | From administration of the drug during surgery to ICU arrival postoperatively (up to 24 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chest Tube Output | Volume of chest tube drainage evaluated over first 24 hours post operatively | From administration end of surgery to 24 hours post operatively | 
| Hours of Mechanical Ventilation |  | From administration of the drug during surgery to extubation in the ICU (up to 30 days) | 
| Length of Stay in Intensive Care Unit (ICU) |  | From administration of the drug during surgery to discharge from the ICU (up to 3 months) | 
| Length of Stay in Hospital |  | From administration of the drug during surgery to discharge from the hospital (up to 6 months) | 
| Count of Participants Who Died Within 30 Days Following Procedure |  | From administration of the drug to 30 days following surgery |