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

NCT03341156 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: STUDY19020099
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

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.

Conditions

Heart Disease End Stage; Heart Failure，Congestive

Keywords

Heart transplantation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (16)

• Postoperative INR

  30 Minutes post-treatment (after the last dose is completed)

• 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)

• 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)

• Need for circulatory support

  30 days post-operative or until discharge (whichever comes first)

• Mechanical Ventilation

  30 days post-operative or until discharge (whichever comes first)

Other Outcomes (5)

• Direct Cost Benefit

  From infusion until 30 days post heart transplant

• Total surgical time

  From anesthesia start time until anesthesia stop time

• Time to hospital discharge

  From patient out of room time to hospital discharge (or 30 days post heart transplant, whichever comes first)

Study Arms (2)

Kcentra (PCC)

EXPERIMENTAL

Half of subjects enrolled will be randomized to the Kcentra (PCC) group.

Drug: Kcentra

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.

Drug: Frozen Plasma Product, Human

Interventions

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)

Also known as: prothrombin complex concentrate

Kcentra (PCC)

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.

Also known as: Fresh Frozen Plasma

Frozen Plasma Product, Human

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• CSL Behring: collaborator

Study Sites (3)

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Upmc Presbyterian Montefiore Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Presbyterian Shadyside

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (17)

• 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.

  PMID: 20881594 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

  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.

  PMID: 25986007 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.

  PMID: 26644327 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.

  PMID: 20840339 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.

  PMID: 23565996 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.

  PMID: 24365268 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.

  PMID: 25281040 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.

  PMID: 18793226 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.

  PMID: 25822921 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.

  PMID: 25728933 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.

  PMID: 26749482 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.

  PMID: 23935011 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.

  PMID: 22735727 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.

  PMID: 22803679 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.

  PMID: 19413730 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.

  PMID: 20435945 BACKGROUND

MeSH Terms

Conditions

Heart Failure

Interventions

Factor IX

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Study Officials

• Kenichi Tanaka, MD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

• Kathirvel Surbramaniam, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2017
• First Posted: November 14, 2017
• Study Start: July 11, 2018
• Primary Completion: September 18, 2020
• Study Completion: February 20, 2025
• Last Updated: May 23, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)