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| Name | Class |
|---|---|
| CSL Behring | INDUSTRY |
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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?
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fresh frozen plasma | Active Comparator | 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. |
|
| Prothrombin complex concentrate | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prothrombin complex concentrate (Human) | Drug | PCC (Kcentra) |
|
| 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 |
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Inclusion Criteria
All subjects accepted for this study must:
Exclusion Criteria
Subjects who have one or more of the following will be excluded from the study:
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| Name | Affiliation | Role |
|---|---|---|
| Gregory Nuttall, MD | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic in Rochester | Rochester | Minnesota | 55905 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22623627 | Background | Arnekian V, Camous J, Fattal S, Rezaiguia-Delclaux S, Nottin R, Stephan F. Use of prothrombin complex concentrate for excessive bleeding after cardiac surgery. Interact Cardiovasc Thorac Surg. 2012 Sep;15(3):382-9. doi: 10.1093/icvts/ivs224. Epub 2012 May 23. | |
| 17599498 | Background | Ballotta A, Saleh HZ, El Baghdady HW, Gomaa M, Belloli F, Kandil H, Balbaa Y, Bettini F, Bossone E, Menicanti L, Frigiola A, Bellucci C, Mehta RH. Comparison of early platelet activation in patients undergoing on-pump versus off-pump coronary artery bypass surgery. J Thorac Cardiovasc Surg. 2007 Jul;134(1):132-8. doi: 10.1016/j.jtcvs.2007.01.055. |
| Label | URL |
|---|---|
| Mayo Clinic Clinical Trials | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Fresh Frozen Plasma | After cardiopulmonary bypass, patients received 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, were collected via preexisting arterial access. If ACT >10% baseline additional protamine was given at the anesthesiologists discretion. Evaluation and determination of excessive microvascular bleeding in the surgical field occurred 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 received 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. Fresh frozen plasma (FFP): FFP |
| FG001 | Prothrombin Complex Concentrate | After cardiopulmonary bypass, patients received 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, were collected via preexisting arterial access. If ACT >10% baseline additional protamine was given at the anesthesiologists discretion. Evaluation and determination of excessive microvascular bleeding in the surgical field occurred 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 received Prothrombin complex concentrate (Human) 15 units/kg. Prothrombin complex concentrate (PCC) (Human): PCC (Kcentra) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Fresh Frozen Plasma | After cardiopulmonary bypass, patients received 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, were collected via preexisting arterial access. If ACT >10% baseline additional protamine was given at the anesthesiologists discretion. Evaluation and determination of excessive microvascular bleeding in the surgical field occurred 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 received 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. Fresh frozen plasma (FFP): FFP |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Chest Tube Output | The amount of chest tube drainage output from after surgery through midnight of the next day. As measured in mL. | 1 subject's data was not collected nor analyzed for the FFP arm | Posted | Median | Inter-Quartile Range | mL | 24 hours |
|
Adverse Events were collected for each subject from baseline to end of study, approximately 30 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Fresh Frozen Plasma | After cardiopulmonary bypass, patients received 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, were collected via preexisting arterial access. If ACT >10% baseline additional protamine was given at the anesthesiologists discretion. Evaluation and determination of excessive microvascular bleeding in the surgical field occurred 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 received 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. Fresh frozen plasma (FFP): FFP |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaphylactic or allergic reaction | Immune system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gregory A. Nuttall, M.D. | Mayo Clinic | (507) 255-3298 | gnuttall@mayo.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 2, 2020 | May 4, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006470 | Hemorrhage |
| D016063 | Blood Loss, Surgical |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007431 | Intraoperative Complications |
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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 |
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| Fresh frozen plasma (FFP) | Biological | FFP |
|
| 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. |
| 23602147 | Background | Ferreira J, DeLosSantos M. The clinical use of prothrombin complex concentrate. J Emerg Med. 2013 Jun;44(6):1201-10. doi: 10.1016/j.jemermed.2012.12.022. Epub 2013 Apr 18. |
| 22621274 | Background | Goldberg AD, Kor DJ. State of the art management of transfusion-related acute lung injury (TRALI). Curr Pharm Des. 2012;18(22):3273-84. doi: 10.2174/1381612811209023273. |
| 21970887 | Background | Gorlinger K, Dirkmann D, Hanke AA, Kamler M, Kottenberg E, Thielmann M, Jakob H, Peters J. First-line therapy with coagulation factor concentrates combined with point-of-care coagulation testing is associated with decreased allogeneic blood transfusion in cardiovascular surgery: a retrospective, single-center cohort study. Anesthesiology. 2011 Dec;115(6):1179-91. doi: 10.1097/ALN.0b013e31823497dd. |
| 20940381 | Background | Hajjar LA, Vincent JL, Galas FR, Nakamura RE, Silva CM, Santos MH, Fukushima J, Kalil Filho R, Sierra DB, Lopes NH, Mauad T, Roquim AC, Sundin MR, Leao WC, Almeida JP, Pomerantzeff PM, Dallan LO, Jatene FB, Stolf NA, Auler JO Jr. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010 Oct 13;304(14):1559-67. doi: 10.1001/jama.2010.1446. |
| 23335567 | Background | Hanke AA, Joch C, Gorlinger K. Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study. Br J Anaesth. 2013 May;110(5):764-72. doi: 10.1093/bja/aes501. Epub 2013 Jan 18. |
| 22315259 | Background | Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, Svensson PJ, Veenstra DL, Crowther M, Guyatt GH. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e152S-e184S. doi: 10.1378/chest.11-2295. |
| 22473649 | Background | Kaatz S, Kouides PA, Garcia DA, Spyropolous AC, Crowther M, Douketis JD, Chan AK, James A, Moll S, Ortel TL, Van Cott EM, Ansell J. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol. 2012 May;87 Suppl 1:S141-5. doi: 10.1002/ajh.23202. Epub 2012 Apr 4. |
| 23416382 | Background | Levy JH, Faraoni D, Spring JL, Douketis JD, Samama CM. Managing new oral anticoagulants in the perioperative and intensive care unit setting. Anesthesiology. 2013 Jun;118(6):1466-74. doi: 10.1097/ALN.0b013e318289bcba. |
| 11388527 | Background | Nuttall GA, Oliver WC, Santrach PJ, Bryant S, Dearani JA, Schaff HV, Ereth MH. Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary bypass. Anesthesiology. 2001 May;94(5):773-81; discussion 5A-6A. doi: 10.1097/00000542-200105000-00014. |
| 22578374 | Background | Pandey S, Vyas GN. Adverse effects of plasma transfusion. Transfusion. 2012 May;52 Suppl 1(Suppl 1):65S-79S. doi: 10.1111/j.1537-2995.2012.03663.x. |
| 22797452 | Background | ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669. |
| 24876232 | Background | Thiele RH, Raphael J. A 2014 Update on Coagulation Management for Cardiopulmonary Bypass. Semin Cardiothorac Vasc Anesth. 2014 Jun;18(2):177-89. doi: 10.1177/1089253214534782. |
| 15818095 | Background | Toy P, Popovsky MA, Abraham E, Ambruso DR, Holness LG, Kopko PM, McFarland JG, Nathens AB, Silliman CC, Stroncek D; National Heart, Lung and Blood Institute Working Group on TRALI. Transfusion-related acute lung injury: definition and review. Crit Care Med. 2005 Apr;33(4):721-6. doi: 10.1097/01.ccm.0000159849.94750.51. |
| 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. |
| 39633218 | Derived | Welsby IJ, Schroeder DR, Ghadimi K, Nuttall GA, Smith MM. Thrombin generation after prothrombin complex concentrate or plasma transfusion during cardiac surgery. J Thromb Thrombolysis. 2025 Feb;58(2):309-318. doi: 10.1007/s11239-024-03061-3. Epub 2024 Dec 4. |
| 36408876 | Derived | Hayes K, Fernando MC, Jordan V. Prothrombin complex concentrate in cardiac surgery for the treatment of coagulopathic bleeding. Cochrane Database Syst Rev. 2022 Nov 21;11(11):CD013551. doi: 10.1002/14651858.CD013551.pub2. |
| 35767271 | Derived | Smith MM, Schroeder DR, Nelson JA, Mauermann WJ, Welsby IJ, Pochettino A, Montonye BL, Assawakawintip C, Nuttall GA. Prothrombin Complex Concentrate vs Plasma for Post-Cardiopulmonary Bypass Coagulopathy and Bleeding: A Randomized Clinical Trial. JAMA Surg. 2022 Sep 1;157(9):757-764. doi: 10.1001/jamasurg.2022.2235. |
| BG001 | Prothrombin Complex Concentrate | After cardiopulmonary bypass, patients received 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, were collected via preexisting arterial access. If ACT >10% baseline additional protamine was given at the anesthesiologists discretion. Evaluation and determination of excessive microvascular bleeding in the surgical field occurred 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 received Prothrombin complex concentrate (Human) 15 units/kg. Prothrombin complex concentrate (Human): PCC (Kcentra) |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Prothrombin Complex Concentrate | After cardiopulmonary bypass, patients received 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, were collected via preexisting arterial access. If ACT >10% baseline additional protamine was given at the anesthesiologists discretion. Evaluation and determination of excessive microvascular bleeding in the surgical field occurred 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 received Prothrombin complex concentrate (Human) 15 units/kg. Prothrombin complex concentrate (Human): PCC (Kcentra) |
|
|
|
| Primary | 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. | 1 subject data was not collected nor analyzed for the FFP arm | Posted | Count of Participants | Participants | 24 hours |
|
|
|
|
| Primary | 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. | 1 subject's data was not collected nor analyzed for the FFP arm | Posted | Count of Participants | Participants | 24 hours |
|
|
|
|
| Primary | 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. | 1 subject's data was not collected nor analyzed for the FFP arm | Posted | Count of Participants | Participants | 24 hours |
|
|
|
|
| Primary | 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. | 1 subject's data was not collected nor analyzed for the FFP arm | Posted | Count of Participants | Participants | 24 hours |
|
|
|
|
| 2 |
| 49 |
| 44 |
| 49 |
| 0 |
| 49 |
| EG001 | Prothrombin Complex Concentrate | After cardiopulmonary bypass, patients received 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, were collected via preexisting arterial access. If ACT >10% baseline additional protamine was given at the anesthesiologists discretion. Evaluation and determination of excessive microvascular bleeding in the surgical field occurred 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 received Prothrombin complex concentrate (Human) 15 units/kg. Prothrombin complex concentrate (Human): PCC (Kcentra) | 1 | 51 | 45 | 51 | 0 | 51 |
| Thromboembolic event | Vascular disorders | Systematic Assessment |
|
| DVT | Vascular disorders | Systematic Assessment |
|
| Mesenteric ischemia | Vascular disorders | Systematic Assessment |
|
| Stroke/TIA | Nervous system disorders | Systematic Assessment |
|
| STEMI | Cardiac disorders | Systematic Assessment |
|
| Renal Failure | Renal and urinary disorders | Systematic Assessment |
|
| Renal Failure requiring dialysis | Renal and urinary disorders | Systematic Assessment |
|
| ARDS | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Prolonged mechanical ventilation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Re-operation | General disorders | Systematic Assessment |
|
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| D011506 |
| Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011498 | Protein Precursors |
| D001685 | Biological Factors |
| 2 units |
|
| 3 or more units |
|
| 2 units |
|
| 3 or more units |
|
| 2 units |
|
| 3 or more units |
|
| 2 units |
|
| 3 or more units |
|