Administration of Prothrombin Complex Concentrate vs. Standard Transfusion During/After Heart Transplantation

Study Overview
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Brief Summary
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This study is comparing the use of Kcentra vs. standard transfusion in patients undergoing heart transplantation surgery. Half of the patients will receive Kcentra, while the other half will receive fresh frozen plasma.

Detailed Description
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This study will be a randomized (1:1; PCC vs. plasma), open-label trial of hemostatic therapies during heart transplantation. The goal is to enroll 60 patients. Informed consent will be obtained from patients meeting the inclusion and exclusion criteria before the initiation of any study specific procedures. Eligible patients will be randomized to receive either PCC or plasma transfusion. The efficacy of interventions will be evaluated after 30 minutes of protamine administration. After the heart transplantation, thrombocytopenia and/or hypofibrinogenemia may worsen bleeding associated with vitamin K dependent factor deficiencies. Transfusion of platelets and/or cryoprecipitate is permitted if abnormal laboratory values are observed during the rewarming phase of CPB; platelet count <100 x 103/µl, and fibrinogen <200 mg/dl, respectively. Laboratory tests (hematocrit, platelet count, PT, PTT, POC-PT, coagulation factor and inhibitor levels (e.g., factor II, antithrombin), thromboelastometry or thromboelastography, endogenous thrombin generation) will also be obtained at baseline, twice during surgery and at 12-24 hours after surgery.

Official Title
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Optimized Administration of Prothrombin Complex Concentrate (PCC) vs. Standard Transfusion During/After Heart Transplantation - OPSTAHT

Conditions
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Heart Disease End Stage, Heart Failure，Congestive

Intervention / Treatment
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* Drug: Kcentra
* Drug: Frozen Plasma Product, Human


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be willing and able to provide written informed consent. Be at least 18 years of age. Patients with or without ventricular assist device (VAD) undergoing heart transplantation Patients who have been on warfarin for at least 72 hours before cardiopulmonary bypass procedures for heart transplantation. International normalization ration (INR) greater than or equal to 1.5 Body temperature greater than 35.0 degrees Celsius. Blood pH greater than 7.2 Hemoglobin greater than 7.0 mg/dL. Exclusion Criteria: Treatment with clopidogrel, prasugrel, or ticagrelor within 5 days prior to study surgery. Known or suspected thrombophilia such as factor V Leiden, hereditary antithrombin III deficiency, heparin-induced thrombocytopenia, disseminated intravascular coagulation. Ischemic or thromboembolic events within 6 weeks of study surgery. Known allergy/anaphylaxis to prothrombin complex concentrate or albumin. Any indication that a potential subject did not comprehend the study restrictions, procedures. or consequences therein an informed consent cannot be convincingly given. Patients on respiratory support including extracorporeal membrane oxygenation (ECMO) . Life expectancy less than 48 hours. Excluded at the discretion of the surgeon based upon surgical safety precautions

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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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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kcentra (PCC)<br>Half of subjects enrolled will be randomized to the Kcentra (PCC) group. | Drug: Kcentra<br>* Kcentra will be administered in 2 divided doses; Pre-bypass (5-10 units/kg based on body weight and preoperative INR and post-protamine based of the pre-bypass dose and the preoperative INR; daily maximum dose not to exceed 5000 IU (50 IU/kg)<br>* Other names: prothrombin complex concentrate;|
| Active Comparator: Frozen Plasma Product, Human<br>Half of subjects enrolled will be randomized to the standard transfusion group and receive fresh frozen plasma intra-operatively. | Drug: Frozen Plasma Product, Human<br>* If the patient is randomized to receive standard transfusion they will receive 2 U of fresh frozen plasma intravenously before cardiopulmonary bypass and then up to 4-8 U of plasma added to the cardiopulmonary bypass reservoir during rewarming.<br>* Other names: Fresh Frozen Plasma;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of Chest Tube Drainage | Primary outcome: Amount of chest tube output in the first 24 hours | From patient out of room time until 24 hours after | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative INR | INR value | 30 Minutes post-treatment (after the last dose is completed) | 
| Blood Product Use | Total hemostatic blood product use including plasma, platelets, cryoprecipitate, and recombinant activated factor VII. | In OR (from OR entry to OR out of room time); postoperatively (patient out of room time) to 24 hours after; from 24 hours after until 30 days post surgery or until discharge (whichever comes first) | 
| Red Blood Cell Use | Red Blood Cell Use Intraoperatively and Postoperatively | Intraoperatively(from start of first intervention until start of second intervention;after 2nd intervention(post-bypass)until patient out of room time) & Postoperatively(from patient out of room time until 24 hours after;24 hours after until 30 days) | 
| Need for circulatory support | Percentage of patients who needed circulatory support (ECMO or VAD) | 30 days post-operative or until discharge (whichever comes first) | 
| Mechanical Ventilation | Percentage of patients who needed mechanical ventilation for more than 72 hours | 30 days post-operative or until discharge (whichever comes first) | 
| Tracheostomy | Percentage of patients who needed a tracheostomy | 30 days post-operative or until discharge (whichever comes first) | 
| Renal Failure | Percentage of patients who experience renal failure requiring dialysis | 30 days post-operative or until discharge (whichever comes first) | 
| Sepsis | Percentage of patients who experienced sepsis infection morbidity consisted of sepsis syndrome, septic shock, or mediastinitis. In addition, the diagnosis of sepsis included organisms isolated from the cultures along with elevated temperature and white blood cell counts. | 30 days post-operative or until discharge (whichever comes first) | 
| Death | Percentage of patients who died | 30 days post-operative or until discharge (whichever comes first) | 
| Stroke or postoperative neurological dysfunction | Percentage of patients who experienced a stroke or postoperative neurological dysfunction (seizures, delirium, unconsciousness, encephalopathy) | 30 days post-operative or until discharge (whichever comes first) | 
| Gastrointestinal complication requiring bowel resection | Percentage of patients who experienced gastrointestinal complications requiring bowel resection | 30 days post-operative or until discharge (whichever comes first) | 
| Peripheral vascular complication | Percentage of patients who experience peripheral vascular complications requiring surgery (thrombectomy, bypass, and amputations) | 30 days post-operative or until discharge (whichever comes first) | 
| Deep Vein Thrombosis and Pulmonary Thromboembolism | Percentage of patients who develop a deep vein thrombosis and/ or pulmonary thromboembolism | 30 days post-operative or until discharge (whichever comes first) | 
| Plasma Coagulation Factor levels | Plasma coagulator factor levels will be analyzed via blood laboratory tests | At baseline, post-bypass/pre-protamine, 30 minutes post-protamine, 12-24 hours post treatment | 
| Thrombin Generation Assay | Thrombin Generation assay will be analyzed via blood laboratory tests | At baseline, post-bypass/pre-protamine, 30 minutes post-protamine, 12-24 hours post treatment | 
| Surgical Re-exploration | Surgical Re-Exploration that is related to heart transplant surgery | 30 days post-operative or until discharge (whichever comes first) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart transplantation