Transfusion of Pathogen Reduced Cryoprecipitated Fibrinogen to Expedite Product Availability in Perioperative Bleeding

Study Overview
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Brief Summary
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The goal of this quality improvement study is to compare pathogen-reduced cryoprecipitate with traditional cryoprecipitate in liver transplant and cardiovascular patients. The investigators hypothesize that by having immediate access to a readily available thawed blood product that replaces fibrinogen (the main substrate of a blood clot), early bleeding can be treated before it escalates into uncontrolled hemorrhage, and therefore additional blood products, like platelets, plasma and red blood cells can be avoided. Participants will be given one of the two FDA-approved blood products.

Detailed Description
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Immediately replacing fibrinogen in perioperative bleeding patients with acquired fibrinogen deficiency improves outcomes. The product that is primarily used for fibrinogen replacement in the US, cryoprecipitate (cryo), must be stored frozen and expires six hours after thawing, resulting in a delay in transfusion of approximately 50 minutes from the time it is ordered, as well as unnecessary transfusion of more readily available but not indicated blood components that are transfused while the patients waits for cryo . A modified version of the product, pathogen reduced (PR) cryo, is now FDA approved and can be thawed and stored for 5 days, allowing the product to be available immediately when needed. In this quality improvement study, the investigators will compare the effect that readily available, pre-thawed PR cryo has on transfusion practice in cardiovascular and liver transplant patients who receive PR cryo versus those who receive traditional cryo by randomizing cryo transfusions in the blood bank by month to all cryo or all PR cryo. All clinical decisions, including the need for cryo, and laboratory testing will occur per standard of care.

Official Title
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Pilot Clinical Trial of Transfusion of Pathogen Reduced Cryoprecipitated Fibrinogen (INTERCEPT Fibrinogen Complex) in Patients With Bleeding to Expedite Product Availability and Improve Outcomes in Perioperative Bleeding

Conditions
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Hypofibrinogenemia, Bleeding

Intervention / Treatment
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* Biological: Traditional Cryoprecipitate
* Biological: Pathogen-Reduced Cryoprecipitate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients undergoing cardiovascular surgery or liver transplant who receive cryo during surgery during the two year study period. Cardiovascular surgery includes the following procedures: coronary artery bypass grafting valve repair or replacement open thoracic aortic and thoracoabdominal aortic surgery atrial or ventricular septal defects ventricular assist device implantation or revision or any combination of the above. Exclusion Criteria: Patients who do not receive any cryo product in the OR Patients who are not cardiovascular surgery or liver transplant patients Cardiac transplantation surgery Patients who receive a product in error within either the cryo time period or the PR cryo time period. For example, PR cryo during a cryo month or cryo during a PR cryo time month. Patients who receive less than 1 pool (5 units) of cryo Pediatric patients (less than 18 years of age). Patients who received both PR cryo and traditional cryo Pregnant women

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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Accepts Healthy Volunteers

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
Interventional Model Description: The intervention and randomization are not made at the level of the individual patient, but rather on clusters of patients by month. The clusters will include all patients at NYP/WC for whom pooled cryo is ordered during a single month.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Patients given Traditional Cryo<br>These are the liver transplant and cardiothoracic (LT and CT) patients that will be given traditional cryo based on the randomization protocol. The blood bank will alternate use of PR cryo and regular cryo each month for all patients with a cryo order. All patients will receive either traditional cryo or PR cryo in a given month. | Biological: Traditional Cryoprecipitate<br>* This is the cryoprecipitate already currently being given to patients with a cryo order.<br>|
| Experimental: Patients given PR Cryo<br>These are the liver transplant and cardiothoracic (LT and CT) patients that will be given PR cryo based on the randomization protocol. The blood bank will alternate use of PR cryo and regular cryo each month for all patients with a cryo order. All patients will receive either traditional cryo or PR cryo in a given month. | Biological: Pathogen-Reduced Cryoprecipitate<br>* This is the pathogen-reduced cryoprecipitate that is intended to be compared to the standard cryoprecipitate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of RBCs used over admission |  | Within the first 30 days after surgery. | 
| Total number of platelets used over admission |  | Within the first 30 days after surgery. | 
| Total number of plasma used over admission |  | Within the first 30 days after surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of cryo or fibrinogen concentrate products used perioperatively |  | 3 days post procedure | 
| Number of RBCs used perioperatively |  | 3 days post procedure | 
| Number of plasma used perioperatively |  | 3 days post procedure | 
| Number of platelets used perioperatively |  | 3 days post procedure | 
| Time from OR start time to start of cryo transfusion |  | procedure (Time from OR start time to start of cryo transfusion) | 
| Time from cryo order to start of transfusion |  | procedure (Time from cryo order to start of transfusion) | 
| Number of cryo units wasted by blood bank |  | Daily, up to approximately 24 months | 
| Pre transfusion FIBTEM amplitude at 10mins |  | Within 10 minutes to one hour after the end of the first cryo transfusion. | 
| Post transfusion FIBTEM amplitude at 10mins |  | Within 10 minutes to one hour after the end of the first cryo transfusion. | 
| Maximum clot firmness at 10mins |  | Within 10 minutes to one hour after the end of the first cryo transfusion. | 
| Fibrinogen level at 10mins |  | Within 10 minutes to one hour after the end of the first cryo transfusion. | 
| Highest fibrinogen level within 24 hours |  | Within 24 hours after surgery | 
| Lowest fibrinogen level within 24 hours |  | Within 24 hours after surgery | 
| Cumulative volume in drains after surgery (e.g., chest tube for CV surgery) at the time of removal |  | Up to approximately 3 days | 
| Volume in drains (e.g. chest tube for CV surgery) |  | At 24 hours after surgery | 
| Time from end of bypass pump for CV surgery |  | Until end of surgery | 
| Length of stay in OR |  | During hospitalization, approximately 5 days to 30 days | 
| Length of stay in ICU |  | During hospitalization, approximately 5 days to 30 days | 
| Length of stay in hospital |  | During hospitalization, approximately 5 days to 30 days | 
| Need for ventilator |  | During hospitalization, approximately 5 days to 30 days | 
| Time on ventilator |  | During hospitalization, approximately 5 days to 30 days | 
| Overall cost of cryo vs PR cryo, when factoring wastage |  | Daily, approximately 24 months | 
| Number of adverse events: fevers | All fevers that occur during the time frame | Within 5 days of surgery start time | 
| Number of adverse events: infections | All infections that occur during the time frame | Within 5 days of surgery start time | 
| Number of adverse events: transfusion reactions | All transfusion reactions that occur during the time frame | Within 5 days of surgery start time | 
| Fibrinogen level |  | Most proximal to end of procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cryoprecipitate, Pathogen Reduced Cryoprecipitate