PCC vs. FFP for Post Cardiopulmonary Bypass Coagulopathy and Bleeding

Study Overview
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Brief Summary
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This will be the first prospective randomized controlled clinical trial directly comparing Prothrombin Complex Concentrate (PCC) Compared to Fresh Frozen Plasma (FFP) for post cardiopulmonary bypass microvascular bleeding and factor-mediated coagulopathy. Is there a difference in bleeding and transfusion requirements in patients received PCC versus FFP?

Official Title
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Prothrombin Complex Concentrate (PCC) Compared to Fresh Frozen Plasma (FFP) for Post-cardiopulmonary Bypass Coagulopathy and Bleeding, a Prospective Randomized Trial at Large US Medical Center.

Conditions
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Bleeding, Blood Loss, Surgical, Cardiovascular Surgical Procedures, Prothrombin Complex Concentrates, Fresh Frozen Plasma

Intervention / Treatment
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* Drug: Prothrombin complex concentrate (Human)
* Biological: Fresh frozen plasma (FFP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria All subjects accepted for this study must: Be 18 years of age Be undergoing elective cardiac surgical procedure utilizing cardiopulmonary bypass Have evidence of excessive microvascular bleeding in the surgical field as determined by the surgical team in addition to a PT >16.6 sec or INR >1.6 sec. Exclusion Criteria Subjects who have one or more of the following will be excluded from the study: Are unable to grant informed consent or comply with study procedure History of hypercoagulable condition (e.g. Factor V Leiden, AT-3 deficiency, Prothrombin gene mutation, Anti-phospholipid antibody syndrome, etc) or previous unprovoked thromboembolic complications Coagulopathic conditions such as factor deficiencies, factor inhibitors, heparin induced thrombocytopenia, or use of intravenous anticoagulants other than heparin at the time of cardiovascular surgery Thromboembolic event within past 3 months Received oral therapy with clopidogrel, prasugrel, rivaroxaban or dabigatran within the past 5 days Patients taking chronic warfarin therapy who have not discontinued treatment and demonstrated an INR <1.3 prior to surgery Fibrinogen level <150 mg/dL on initial post cardiopulmonary bypass labs Antithrombin 3 level < 80% control (preoperative) Are undergoing emergency open heart-surgery Cardiopulmonary bypass time is expected to be < 30 minutes Age < 18 years of age Are pregnant

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fresh frozen plasma<br>After cardiopulmonary bypass, patients will receive protamine at dose 0.01 mg/unit of heparin given with target activated clotting time (ACT) within 10% of baseline value. After protamine administration the ACT, complete blood count (CBC), prothrombin time (PT)/ international normalized ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen, will be collected via preexisting arterial access. If ACT >10% baseline additional protamine will be given at the anesthesiologists discretion. Evaluation and determination of excessive microvascular bleeding in the surgical field will occur 10 minutes after return of ACT to within 10% of baseline. Patients with clinical evidence of excessive microvascular bleeding in the surgical field as determined by the surgical team, along with a PT >16.6 sec/ INR >1.6 sec will receive fresh frozen plasma as this is standard therapy per our institutional algorithm at a dose of 10-15 mL/kg rounded up to the nearest unit. | Biological: Fresh frozen plasma (FFP)<br>* FFP<br>|
| Experimental: Prothrombin complex concentrate<br>After cardiopulmonary bypass, patients will receive protamine at dose 0.01 mg/unit of heparin given with target ACT within 10% of baseline value. After protamine administration the ACT, CBC, PT/ INR, APTT, and fibrinogen, will be collected via preexisting arterial access. If ACT >10% baseline additional protamine will be given at the anesthesiologists discretion. Evaluation and determination of excessive microvascular bleeding in the surgical field will occur 10 minutes after return of ACT to within 10% of baseline. Patients with clinical evidence of excessive microvascular bleeding in the surgical field as determined by the surgical team, along with a PT >16.6 sec/ INR >1.6 sec will receive Prothrombin complex concentrate (Human) 15 units/kg. | Drug: Prothrombin complex concentrate (Human)<br>* PCC (Kcentra)<br>* Other names: Kcentra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chest Tube Output | The amount of chest tube drainage output from after surgery through midnight of the next day. As measured in mL. | 24 hours | 
| Red Blood Cell (RBC) Blood Product Transfusion | The number of subject's who received 0,1,2,3 or more units of RBC's transfused from completion of study drug administration though midnight of the next day. | 24 hours | 
| Platelets Blood Product Transfusion | The number of subject's who received 0,1,2,3 or more units of Platelets transfused from completion of study drug administration though midnight of the next day. | 24 hours | 
| Cryoprecipitate (Cryo) Blood Product Transfusion | The number of subject's who received 0,1,2,3 or more units of Cryo's transfused from completion of study drug administration though midnight of the next day. | 24 hours | 
| Fresh Frozen Plasma (FFP) Blood Product Transfusion | The number of subject's who received 0,1,2,3 or more units of FFP's transfused from completion of study drug administration though midnight of the next day. | 24 hours |