search
Back to results

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

Primary Purpose

Heart Disease End Stage, Heart Failure，Congestive

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Kcentra
Frozen Plasma Product, Human
Sponsored by
Kathirvel Subramaniam
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Disease End Stage focused on measuring Heart transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of MarylandRecruiting
  • Upmc Presbyterian Montefiore Hospital
  • UPMC Presbyterian Shadyside

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Kcentra (PCC)

Frozen Plasma Product, Human

Arm Description

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

Half of subjects enrolled will be randomized to the standard transfusion group and receive fresh frozen plasma intra-operatively.

Outcomes

Primary Outcome Measures

Amount of Chest Tube Drainage
Primary outcome: Amount of chest tube output in the first 24 hours

Secondary Outcome Measures

Postoperative INR
INR value
Blood Product Use
Total hemostatic blood product use including plasma, platelets, cryoprecipitate, and recombinant activated factor VII.
Red Blood Cell Use
Red Blood Cell Use Intraoperatively and Postoperatively
Need for circulatory support
Percentage of patients who needed circulatory support (ECMO or VAD)
Mechanical Ventilation
Percentage of patients who needed mechanical ventilation for more than 72 hours
Tracheostomy
Percentage of patients who needed a tracheostomy
Renal Failure
Percentage of patients who experience renal failure requiring dialysis
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.
Death
Percentage of patients who died
Stroke or postoperative neurological dysfunction
Percentage of patients who experienced a stroke or postoperative neurological dysfunction (seizures, delirium, unconsciousness, encephalopathy)
Gastrointestinal complication requiring bowel resection
Percentage of patients who experienced gastrointestinal complications requiring bowel resection
Peripheral vascular complication
Percentage of patients who experience peripheral vascular complications requiring surgery (thrombectomy, bypass, and amputations)
Deep Vein Thrombosis and Pulmonary Thromboembolism
Percentage of patients who develop a deep vein thrombosis and/ or pulmonary thromboembolism
Plasma Coagulation Factor levels
Plasma coagulator factor levels will be analyzed via blood laboratory tests
Thrombin Generation Assay
Thrombin Generation assay will be analyzed via blood laboratory tests
Surgical Re-exploration
Surgical Re-Exploration that is related to heart transplant surgery

Full Information

First Posted
August 28, 2017
Last Updated
July 25, 2023
Sponsor
Kathirvel Subramaniam
Collaborators
University of Maryland, Baltimore, CSL Behring
search

1. Study Identification

Unique Protocol Identification Number
NCT03341156
Brief Title
Administration of Prothrombin Complex Concentrate vs. Standard Transfusion During/After Heart Transplantation
Acronym
OPSTAHT
Official Title
Optimized Administration of Prothrombin Complex Concentrate (PCC) vs. Standard Transfusion During/After Heart Transplantation - OPSTAHT
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 11, 2018 (Actual)
Primary Completion Date
October 1, 2023 (Anticipated)
Study Completion Date
December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Kathirvel Subramaniam
Collaborators
University of Maryland, Baltimore, CSL Behring

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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/Β΅l, 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Disease End Stage, Heart Failure，Congestive
Keywords
Heart transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Kcentra (PCC)
Arm Type
Experimental
Arm Description
Half of subjects enrolled will be randomized to the Kcentra (PCC) group.
Arm Title
Frozen Plasma Product, Human
Arm Type
Active Comparator
Arm Description
Half of subjects enrolled will be randomized to the standard transfusion group and receive fresh frozen plasma intra-operatively.
Intervention Type
Drug
Intervention Name(s)
Kcentra
Other Intervention Name(s)
prothrombin complex concentrate
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Frozen Plasma Product, Human
Other Intervention Name(s)
Fresh Frozen Plasma
Intervention Description
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.
Primary Outcome Measure Information:
Title
Amount of Chest Tube Drainage
Description
Primary outcome: Amount of chest tube output in the first 24 hours
Time Frame
From patient out of room time until 24 hours after
Secondary Outcome Measure Information:
Title
Postoperative INR
Description
INR value
Time Frame
30 Minutes post-treatment (after the last dose is completed)
Title
Blood Product Use
Description
Total hemostatic blood product use including plasma, platelets, cryoprecipitate, and recombinant activated factor VII.
Time Frame
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)
Title
Red Blood Cell Use
Description
Red Blood Cell Use Intraoperatively and Postoperatively
Time Frame
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)
Title
Need for circulatory support
Description
Percentage of patients who needed circulatory support (ECMO or VAD)
Time Frame
30 days post-operative or until discharge (whichever comes first)
Title
Mechanical Ventilation
Description
Percentage of patients who needed mechanical ventilation for more than 72 hours
Time Frame
30 days post-operative or until discharge (whichever comes first)
Title
Tracheostomy
Description
Percentage of patients who needed a tracheostomy
Time Frame
30 days post-operative or until discharge (whichever comes first)
Title
Renal Failure
Description
Percentage of patients who experience renal failure requiring dialysis
Time Frame
30 days post-operative or until discharge (whichever comes first)
Title
Sepsis
Description
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.
Time Frame
30 days post-operative or until discharge (whichever comes first)
Title
Death
Description
Percentage of patients who died
Time Frame
30 days post-operative or until discharge (whichever comes first)
Title
Stroke or postoperative neurological dysfunction
Description
Percentage of patients who experienced a stroke or postoperative neurological dysfunction (seizures, delirium, unconsciousness, encephalopathy)
Time Frame
30 days post-operative or until discharge (whichever comes first)
Title
Gastrointestinal complication requiring bowel resection
Description
Percentage of patients who experienced gastrointestinal complications requiring bowel resection
Time Frame
30 days post-operative or until discharge (whichever comes first)
Title
Peripheral vascular complication
Description
Percentage of patients who experience peripheral vascular complications requiring surgery (thrombectomy, bypass, and amputations)
Time Frame
30 days post-operative or until discharge (whichever comes first)
Title
Deep Vein Thrombosis and Pulmonary Thromboembolism
Description
Percentage of patients who develop a deep vein thrombosis and/ or pulmonary thromboembolism
Time Frame
30 days post-operative or until discharge (whichever comes first)
Title
Plasma Coagulation Factor levels
Description
Plasma coagulator factor levels will be analyzed via blood laboratory tests
Time Frame
At baseline, post-bypass/pre-protamine, 30 minutes post-protamine, 12-24 hours post treatment
Title
Thrombin Generation Assay
Description
Thrombin Generation assay will be analyzed via blood laboratory tests
Time Frame
At baseline, post-bypass/pre-protamine, 30 minutes post-protamine, 12-24 hours post treatment
Title
Surgical Re-exploration
Description
Surgical Re-Exploration that is related to heart transplant surgery
Time Frame
30 days post-operative or until discharge (whichever comes first)
Other Pre-specified Outcome Measures:
Title
Direct Cost Benefit
Description
Acquisition costs for test agents and blood bank related charges (thawing, etc.)
Time Frame
From infusion until 30 days post heart transplant
Title
Total surgical time
Description
Total time of surgical duration will be measured in the corresponding time frame
Time Frame
From anesthesia start time until anesthesia stop time
Title
Time to hospital discharge
Description
Time until discharge from the hospital post study intervention will be measured
Time Frame
From patient out of room time to hospital discharge (or 30 days post heart transplant, whichever comes first)
Title
Time to Intensive Care Unit (ICU) discharge
Description
Time until discharge from the ICU post study intervention will be measured
Time Frame
From patient out of room time to ICU discharge (or 30 days post heart transplant, whichever comes first)
Title
Indirect Cost Benefits
Description
Extra costs related to study drug (PCC and plasma) related complications (volume overload, thrombotic complications)
Time Frame
From last intervention/infusion until 30 days post heart transplant or until discharge

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amy Monroe
Phone
412-623-6382
Email
Monroeal@upmc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Caroline E. Kostishack
Phone
412-623-1586
Email
caroline.kostishack@chp.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kenichi Tanaka, MD
Organizational Affiliation
University of Maryland Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kathirvel Surbramaniam, MD
Organizational Affiliation
University of Pittsburgh Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kenichi Tanaka, M.D.
Phone
410-328-9813
First Name & Middle Initial & Last Name & Degree
LaToya Stubbs
Email
lstubbs@som.umaryland.edu
Facility Name
Upmc Presbyterian Montefiore Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
KATHIRVEL SUBRAMANIAM, MD
Phone
412-647-5635
Email
subramaniamk@upmc.edu
First Name & Middle Initial & Last Name & Degree
AMY MONROE, MPH
Phone
4126096161
Email
monroeal@upmc.edu
Facility Name
UPMC Presbyterian Shadyside
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Individual Site Status
Terminated

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
20881594
Citation
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.
Results Reference
background
Citation
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
Results Reference
background
PubMed Identifier
25986007
Citation
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.
Results Reference
background
PubMed Identifier
26644327
Citation
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.
Results Reference
background
PubMed Identifier
20840339
Citation
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.
Results Reference
background
PubMed Identifier
23565996
Citation
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.
Results Reference
background
PubMed Identifier
24365268
Citation
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.
Results Reference
background
PubMed Identifier
25281040
Citation
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.
Results Reference
background
PubMed Identifier
18793226
Citation
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.
Results Reference
background
PubMed Identifier
25822921
Citation
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.
Results Reference
background
PubMed Identifier
25728933
Citation
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.
Results Reference
background
PubMed Identifier
26749482
Citation
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.
Results Reference
background
PubMed Identifier
23935011
Citation
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.
Results Reference
background
PubMed Identifier
22735727
Citation
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.
Results Reference
background
PubMed Identifier
22803679
Citation
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.
Results Reference
background
PubMed Identifier
19413730
Citation
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.
Results Reference
background
PubMed Identifier
20435945
Citation
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.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs