Heart Disease End Stage, Heart Failure，Congestive
Conditions
Keywords
Heart transplantation
Brief summary
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
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.
Interventions
DRUGKcentra
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)
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.
Sponsors
CSL Behring
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amount of Chest Tube Drainage | From patient out of room time until 24 hours after | Primary outcome: Amount of chest tube output in the first 24 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal Failure | 30 days post-operative or until discharge (whichever comes first) | Percentage of patients who experience renal failure requiring dialysis |
| Peripheral vascular complication | 30 days post-operative or until discharge (whichever comes first) | Percentage of patients who experience peripheral vascular complications requiring surgery (thrombectomy, bypass, and amputations) |
| Deep Vein Thrombosis and Pulmonary Thromboembolism | 30 days post-operative or until discharge (whichever comes first) | Percentage of patients who develop a deep vein thrombosis and/ or pulmonary thromboembolism |
| Plasma Coagulation Factor levels | At baseline, post-bypass/pre-protamine, 30 minutes post-protamine, 12-24 hours post treatment | Plasma coagulator factor levels will be analyzed via blood laboratory tests |
| Thrombin Generation Assay | At baseline, post-bypass/pre-protamine, 30 minutes post-protamine, 12-24 hours post treatment | Thrombin Generation assay will be analyzed via blood laboratory tests |
| Surgical Re-exploration | 30 days post-operative or until discharge (whichever comes first) | Surgical Re-Exploration that is related to heart transplant surgery |
| Postoperative INR | 30 Minutes post-treatment (after the last dose is completed) | INR value |
| Blood Product Use | 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) | Total hemostatic blood product use including plasma, platelets, cryoprecipitate, and recombinant activated factor VII. |
| Red Blood Cell Use | 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) | Red Blood Cell Use Intraoperatively and Postoperatively |
| Need for circulatory support | 30 days post-operative or until discharge (whichever comes first) | Percentage of patients who needed circulatory support (ECMO or VAD) |
| Mechanical Ventilation | 30 days post-operative or until discharge (whichever comes first) | Percentage of patients who needed mechanical ventilation for more than 72 hours |
| Tracheostomy | 30 days post-operative or until discharge (whichever comes first) | Percentage of patients who needed a tracheostomy |
| Sepsis | 30 days post-operative or until discharge (whichever comes first) | 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. |
| Death | 30 days post-operative or until discharge (whichever comes first) | Percentage of patients who died |
| Stroke or postoperative neurological dysfunction | 30 days post-operative or until discharge (whichever comes first) | Percentage of patients who experienced a stroke or postoperative neurological dysfunction (seizures, delirium, unconsciousness, encephalopathy) |
| Gastrointestinal complication requiring bowel resection | 30 days post-operative or until discharge (whichever comes first) | Percentage of patients who experienced gastrointestinal complications requiring bowel resection |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to hospital discharge | From patient out of room time to hospital discharge (or 30 days post heart transplant, whichever comes first) | Time until discharge from the hospital post study intervention will be measured |
| Time to Intensive Care Unit (ICU) discharge | From patient out of room time to ICU discharge (or 30 days post heart transplant, whichever comes first) | Time until discharge from the ICU post study intervention will be measured |
| Indirect Cost Benefits | From last intervention/infusion until 30 days post heart transplant or until discharge | Extra costs related to study drug (PCC and plasma) related complications (volume overload, thrombotic complications) |
| Direct Cost Benefit | From infusion until 30 days post heart transplant | Acquisition costs for test agents and blood bank related charges (thawing, etc.) |
| Total surgical time | From anesthesia start time until anesthesia stop time | Total time of surgical duration will be measured in the corresponding time frame |
Countries
United States
Outcome results
None listed