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

Sponsor
Kathirvel Subramaniam (Other)
Overall Status
Recruiting
CT.gov ID
NCT03341156
Collaborator
University of Maryland, Baltimore (Other), CSL Behring (Industry)
60
Enrollment
3
Locations
2
Arms
52.7
Anticipated Duration (Months)
20
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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/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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Optimized Administration of Prothrombin Complex Concentrate (PCC) vs. Standard Transfusion During/After Heart Transplantation - OPSTAHT
Actual Study Start Date :
Jul 11, 2018
Anticipated Primary Completion Date :
Oct 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Kcentra (PCC)

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

Drug: Kcentra
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)
Other Names:
  • prothrombin complex concentrate

    		•
    Active Comparator: Frozen Plasma Product, Human

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

    Drug: Frozen Plasma Product, Human
    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.
    Other Names:
  • Fresh Frozen Plasma

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Amount of Chest Tube Drainage [From patient out of room time until 24 hours after]

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

    Secondary Outcome Measures

    1. Postoperative INR [30 Minutes post-treatment (after the last dose is completed)]

      INR value

    2. 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)]

      Total hemostatic blood product use including plasma, platelets, cryoprecipitate, and recombinant activated factor VII.

    3. 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)]

      Red Blood Cell Use Intraoperatively and Postoperatively

    4. Need for circulatory support [30 days post-operative or until discharge (whichever comes first)]

      Percentage of patients who needed circulatory support (ECMO or VAD)

    5. Mechanical Ventilation [30 days post-operative or until discharge (whichever comes first)]

      Percentage of patients who needed mechanical ventilation for more than 72 hours

    6. Tracheostomy [30 days post-operative or until discharge (whichever comes first)]

      Percentage of patients who needed a tracheostomy

    7. Renal Failure [30 days post-operative or until discharge (whichever comes first)]

      Percentage of patients who experience renal failure requiring dialysis

    8. Sepsis [30 days post-operative or until discharge (whichever comes first)]

      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.

    9. Death [30 days post-operative or until discharge (whichever comes first)]

      Percentage of patients who died

    10. Stroke or postoperative neurological dysfunction [30 days post-operative or until discharge (whichever comes first)]

      Percentage of patients who experienced a stroke or postoperative neurological dysfunction (seizures, delirium, unconsciousness, encephalopathy)

    11. Gastrointestinal complication requiring bowel resection [30 days post-operative or until discharge (whichever comes first)]

      Percentage of patients who experienced gastrointestinal complications requiring bowel resection

    12. Peripheral vascular complication [30 days post-operative or until discharge (whichever comes first)]

      Percentage of patients who experience peripheral vascular complications requiring surgery (thrombectomy, bypass, and amputations)

    13. Deep Vein Thrombosis and Pulmonary Thromboembolism [30 days post-operative or until discharge (whichever comes first)]

      Percentage of patients who develop a deep vein thrombosis and/ or pulmonary thromboembolism

    14. Plasma Coagulation Factor levels [At baseline, post-bypass/pre-protamine, 30 minutes post-protamine, 12-24 hours post treatment]

      Plasma coagulator factor levels will be analyzed via blood laboratory tests

    15. Thrombin Generation Assay [At baseline, post-bypass/pre-protamine, 30 minutes post-protamine, 12-24 hours post treatment]

      Thrombin Generation assay will be analyzed via blood laboratory tests

    16. Surgical Re-exploration [30 days post-operative or until discharge (whichever comes first)]

      Surgical Re-Exploration that is related to heart transplant surgery

    Other Outcome Measures

    1. Direct Cost Benefit [From infusion until 30 days post heart transplant]

      Acquisition costs for test agents and blood bank related charges (thawing, etc.)

    2. Total surgical time [From anesthesia start time until anesthesia stop time]

      Total time of surgical duration will be measured in the corresponding time frame

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

      Time until discharge from the hospital post study intervention will be measured

    4. Time to Intensive Care Unit (ICU) discharge [From patient out of room time to ICU discharge (or 30 days post heart transplant, whichever comes first)]

      Time until discharge from the ICU post study intervention will be measured

    5. Indirect Cost Benefits [From last intervention/infusion until 30 days post heart transplant or until discharge]

      Extra costs related to study drug (PCC and plasma) related complications (volume overload, thrombotic complications)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Maryland Baltimore Maryland United States 21201
    2 Upmc Presbyterian Montefiore Hospital Pittsburgh Pennsylvania United States 15213
    3 UPMC Presbyterian Shadyside Pittsburgh Pennsylvania United States 15213

    Sponsors and Collaborators

    • Kathirvel Subramaniam
    • University of Maryland, Baltimore
    • CSL Behring

    Investigators

    • Principal Investigator: Kenichi Tanaka, MD, University of Maryland Medical Center
    • Principal Investigator: Kathirvel Surbramaniam, MD, University of Pittsburgh Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Kathirvel Subramaniam, Principal Investigator, University of Pittsburgh
    ClinicalTrials.gov Identifier:
    NCT03341156
    Other Study ID Numbers:
    • PRO17080509
    First Posted:
    Nov 14, 2017
    Last Update Posted:
    Jan 11, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by Kathirvel Subramaniam, Principal Investigator, University of Pittsburgh
    Heart transplantation
    Additional relevant MeSH terms:
    Heart Failure
    Heart Diseases
    Thrombin

    Study Results

    No Results Posted as of Jan 11, 2022