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Standard practice change prohibited enrollment
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| Name | Class |
|---|---|
| CSL Behring | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Kcentra (PCC) | Experimental | Half of subjects enrolled will be randomized to the Kcentra (PCC) group. |
|
| Frozen Plasma Product, Human | Active Comparator | Half of subjects enrolled will be randomized to the standard transfusion group and receive fresh frozen plasma intra-operatively. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Kcentra | Drug | 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) |
| 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 |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Direct Cost Benefit | Acquisition costs for test agents and blood bank related charges (thawing, etc.) | From infusion until 30 days post heart transplant |
| Total surgical time | Total time of surgical duration will be measured in the corresponding time frame |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kenichi Tanaka, MD | University of Maryland, Baltimore | Principal Investigator |
| Kathirvel Surbramaniam, MD | University of Pittsburgh Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland | Baltimore | Maryland | 21201 | United States | ||
| Upmc Presbyterian Montefiore Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20881594 | Background | Bolliger D, Gorlinger K, Tanaka KA. Pathophysiology and treatment of coagulopathy in massive hemorrhage and hemodilution. Anesthesiology. 2010 Nov;113(5):1205-19. doi: 10.1097/ALN.0b013e3181f22b5a. | |
| Background | Mathias T, Puca KE, Downey F, Boyle AJ: Use of Vitamin K and Prothrombin Complex Concentrate as Warfarin Reversal Prior to Heart Transplant. Journal of Heart and Lung Transplantation 2012; 31: S154 | ||
| 25986007 |
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|
| Frozen Plasma Product, Human | Drug | 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. |
|
|
| 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) |
| From anesthesia start time until anesthesia stop time |
| Time to hospital discharge | Time until discharge from the hospital post study intervention will be measured | From patient out of room time to hospital discharge (or 30 days post heart transplant, whichever comes first) |
| Time to Intensive Care Unit (ICU) discharge | Time until discharge from the ICU post study intervention will be measured | From patient out of room time to ICU discharge (or 30 days post heart transplant, whichever comes first) |
| Indirect Cost Benefits | Extra costs related to study drug (PCC and plasma) related complications (volume overload, thrombotic complications) | From last intervention/infusion until 30 days post heart transplant or until discharge |
| Pittsburgh |
| Pennsylvania |
| 15213 |
| United States |
| UPMC Presbyterian Shadyside | Pittsburgh | Pennsylvania | 15213 | United States |
| Background |
| Kantorovich A, Fink JM, Militello MA, Wanek MR, Smedira NG, Soltesz EG, Moazami N. Low-dose 3-factor prothrombin complex concentrate for warfarin reversal prior to heart transplant. Ann Pharmacother. 2015 Aug;49(8):876-82. doi: 10.1177/1060028015585344. Epub 2015 May 18. |
| 26644327 | Background | Marshall AL, Levine M, Howell ML, Chang Y, Riklin E, Parry BA, Callahan RT, Okechukwu I, Ayres AM, Nahed BV, Goldstein JN. Dose-associated pulmonary complication rates after fresh frozen plasma administration for warfarin reversal. J Thromb Haemost. 2016 Feb;14(2):324-30. doi: 10.1111/jth.13212. Epub 2016 Feb 2. |
| 20840339 | Background | Demeyere R, Gillardin S, Arnout J, Strengers PF. Comparison of fresh frozen plasma and prothrombin complex concentrate for the reversal of oral anticoagulants in patients undergoing cardiopulmonary bypass surgery: a randomized study. Vox Sang. 2010 Oct;99(3):251-60. doi: 10.1111/j.1423-0410.2010.01339.x. |
| 23565996 | Background | Tanaka KA, Mazzeffi MA, Grube M, Ogawa S, Chen EP. Three-factor prothrombin complex concentrate and hemostasis after high-risk cardiovascular surgery. Transfusion. 2013 Apr;53(4):920-1. doi: 10.1111/trf.12110. No abstract available. |
| 24365268 | Background | Song HK, Tibayan FA, Kahl EA, Sera VA, Slater MS, Deloughery TG, Scanlan MM. Safety and efficacy of prothrombin complex concentrates for the treatment of coagulopathy after cardiac surgery. J Thorac Cardiovasc Surg. 2014 Mar;147(3):1036-40. doi: 10.1016/j.jtcvs.2013.11.020. Epub 2013 Dec 22. |
| 25281040 | Background | Rao VK, Lobato RL, Bartlett B, Klanjac M, Mora-Mangano CT, Soran PD, Oakes DA, Hill CC, van der Starre PJ. Factor VIII inhibitor bypass activity and recombinant activated factor VII in cardiac surgery. J Cardiothorac Vasc Anesth. 2014 Oct;28(5):1221-6. doi: 10.1053/j.jvca.2014.04.015. |
| 18793226 | Background | Balsam LB, Timek TA, Pelletier MP. Factor eight inhibitor bypassing activity (FEIBA) for refractory bleeding in cardiac surgery: review of clinical outcomes. J Card Surg. 2008 Nov-Dec;23(6):614-21. doi: 10.1111/j.1540-8191.2008.00686.x. Epub 2008 Sep 10. |
| 25822921 | Background | Ortmann E, Besser MW, Sharples LD, Gerrard C, Berman M, Jenkins DP, Klein AA. An exploratory cohort study comparing prothrombin complex concentrate and fresh frozen plasma for the treatment of coagulopathy after complex cardiac surgery. Anesth Analg. 2015 Jul;121(1):26-33. doi: 10.1213/ANE.0000000000000689. |
| 25728933 | Background | Goldstein JN, Refaai MA, Milling TJ Jr, Lewis B, Goldberg-Alberts R, Hug BA, Sarode R. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet. 2015 May 23;385(9982):2077-87. doi: 10.1016/S0140-6736(14)61685-8. Epub 2015 Feb 27. |
| 26749482 | Background | Tanaka KA, Mazzeffi MA, Strauss ER, Szlam F, Guzzetta NA. Computational simulation and comparison of prothrombin complex concentrate dosing schemes for warfarin reversal in cardiac surgery. J Anesth. 2016 Jun;30(3):369-76. doi: 10.1007/s00540-015-2128-3. Epub 2016 Jan 9. |
| 23935011 | Background | Sarode R, Milling TJ Jr, Refaai MA, Mangione A, Schneider A, Durn BL, Goldstein JN. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013 Sep 10;128(11):1234-43. doi: 10.1161/CIRCULATIONAHA.113.002283. Epub 2013 Aug 9. |
| 22735727 | Background | Subramaniam K. Early graft failure after heart transplantation: prevention and treatment. Int Anesthesiol Clin. 2012 Summer;50(3):202-27. doi: 10.1097/AIA.0b013e3182603ead. No abstract available. |
| 22803679 | Background | Tholpady A, Monson J, Radovancevic R, Klein K, Bracey A. Analysis of prolonged storage on coagulation Factor (F)V, FVII, and FVIII in thawed plasma: is it time to extend the expiration date beyond 5 days? Transfusion. 2013 Mar;53(3):645-50. doi: 10.1111/j.1537-2995.2012.03786.x. Epub 2012 Jul 15. |
| 19413730 | Background | Scott E, Puca K, Heraly J, Gottschall J, Friedman K. Evaluation and comparison of coagulation factor activity in fresh-frozen plasma and 24-hour plasma at thaw and after 120 hours of 1 to 6 degrees C storage. Transfusion. 2009 Aug;49(8):1584-91. doi: 10.1111/j.1537-2995.2009.02198.x. |
| 20435945 | Background | Karkouti K, McCluskey SA, Syed S, Pazaratz C, Poonawala H, Crowther MA. The influence of perioperative coagulation status on postoperative blood loss in complex cardiac surgery: a prospective observational study. Anesth Analg. 2010 Jun 1;110(6):1533-40. doi: 10.1213/ANE.0b013e3181db7991. Epub 2010 Apr 30. |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D005164 | Factor IX |
| ID | Term |
|---|---|
| D004792 | Enzyme Precursors |
| D045762 | Enzymes and Coenzymes |
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011498 | Protein Precursors |
| D001685 | Biological Factors |
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