PCC vs. FFP for Post Cardiopulmonary Bypass Coagulopathy and Bleeding

NCT ID: NCT02557672

Last Updated: 2022-06-07

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

106 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-08-31

Study Completion Date

2022-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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?

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Fresh frozen plasma

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.

Group Type ACTIVE_COMPARATOR

Fresh frozen plasma (FFP)

Intervention Type BIOLOGICAL

FFP

Prothrombin complex concentrate

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.

Group Type EXPERIMENTAL

Prothrombin complex concentrate (Human)

Intervention Type DRUG

PCC (Kcentra)

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Prothrombin complex concentrate (Human)

PCC (Kcentra)

Intervention Type DRUG

Fresh frozen plasma (FFP)

FFP

Intervention Type BIOLOGICAL

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Kcentra

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

CSL Behring

INDUSTRY

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Gregory A. Nuttall, M.D.

PI

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Gregory Nuttall, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 22623627 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17599498 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20840339 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23602147 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22621274 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21970887 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20940381 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23335567 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22315259 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22473649 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23416382 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11388527 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22578374 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22797452 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24876232 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15818095 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25822921 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39633218 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36408876 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35767271 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

14-009579

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Factor Replacement in Surgery
NCT04114643 UNKNOWN PHASE2