Clinical trial NCT03341156: Administration of Prothrombin Complex Concentrate vs. Standard Transfusion During/After Heart Transplantation
Official title: Optimized Administration of Prothrombin Complex Concentrate (PCC) vs. Standard Transfusion During/After Heart Transplantation - OPSTAHT
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Heart Disease End Stage
Heart Failure，Congestive
Keywords: Heart transplantation
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: CSL Behring
First posted: 2017-11-14
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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/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.

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

Primary outcomes:
measure: Amount of Chest Tube Drainage
timeFrame: From patient out of room time until 24 hours after
Secondary outcomes:
measure: Postoperative INR
timeFrame: 30 Minutes post-treatment (after the last dose is completed)
measure: Blood Product Use
timeFrame: 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)
measure: Red Blood Cell Use
timeFrame: 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)
measure: Need for circulatory support
timeFrame: 30 days post-operative or until discharge (whichever comes first)
measure: Mechanical Ventilation
timeFrame: 30 days post-operative or until discharge (whichever comes first)
measure: Tracheostomy
timeFrame: 30 days post-operative or until discharge (whichever comes first)
measure: Renal Failure
timeFrame: 30 days post-operative or until discharge (whichever comes first)
measure: Sepsis
timeFrame: 30 days post-operative or until discharge (whichever comes first)
measure: Death
timeFrame: 30 days post-operative or until discharge (whichever comes first)
measure: Stroke or postoperative neurological dysfunction
timeFrame: 30 days post-operative or until discharge (whichever comes first)
measure: Gastrointestinal complication requiring bowel resection
timeFrame: 30 days post-operative or until discharge (whichever comes first)
measure: Peripheral vascular complication
timeFrame: 30 days post-operative or until discharge (whichever comes first)
measure: Deep Vein Thrombosis and Pulmonary Thromboembolism
timeFrame: 30 days post-operative or until discharge (whichever comes first)
measure: Plasma Coagulation Factor levels
timeFrame: At baseline, post-bypass/pre-protamine, 30 minutes post-protamine, 12-24 hours post treatment
measure: Thrombin Generation Assay
timeFrame: At baseline, post-bypass/pre-protamine, 30 minutes post-protamine, 12-24 hours post treatment
measure: Surgical Re-exploration
timeFrame: 30 days post-operative or until discharge (whichever comes first)
Other outcomes:
measure: Direct Cost Benefit
timeFrame: From infusion until 30 days post heart transplant
measure: Total surgical time
timeFrame: From anesthesia start time until anesthesia stop time
measure: Time to hospital discharge
timeFrame: From patient out of room time to hospital discharge (or 30 days post heart transplant, whichever comes first)
measure: Time to Intensive Care Unit (ICU) discharge
timeFrame: From patient out of room time to ICU discharge (or 30 days post heart transplant, whichever comes first)
measure: Indirect Cost Benefits
timeFrame: From last intervention/infusion until 30 days post heart transplant or until discharge
Locations:
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Pittsburgh
country: United States
facility: Upmc Presbyterian Montefiore Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Shadyside
state: Pennsylvania
Study officials:
affiliation: University of Maryland, Baltimore
name: Kenichi Tanaka, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh Medical Center
name: Kathirvel Surbramaniam, MD
role: PRINCIPAL_INVESTIGATOR
References:
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