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

Phase 3

Recruiting

• Conditions: Heart Disease End Stage; Heart Failure，Congestive
• Interventions: Drug: Frozen Plasma Product, Human; Drug: Kcentra

• Registration Number: NCT03341156
• Lead Sponsor: Kathirvel Subramaniam

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.

Study Timeline

• Study First Submitted: 2017-08-28
• Study First Submitted QC: 2017-11-09
• Study First Posted: 2017-11-14
• Study Start: 2018-07-11
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-04
• Last Update Posted: 2024-01-08
• Primary Completion: 2024-10-01
• Study Completion: 2024-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Frozen Plasma Product, Human	Frozen Plasma Product, Human	Half of subjects enrolled will be randomized to the standard transfusion group and receive fresh frozen plasma intra-operatively.
Kcentra (PCC)	Kcentra	Half of subjects enrolled will be randomized to the Kcentra (PCC) group.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
Renal Failure	30 days post-operative or until discharge (whichever comes first)	Percentage of patients who experience renal failure requiring dialysis
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
Mechanical Ventilation	30 days post-operative or until discharge (whichever comes first)	Percentage of patients who needed mechanical ventilation for more than 72 hours
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)
Need for circulatory support	30 days post-operative or until discharge (whichever comes first)	Percentage of patients who needed circulatory support (ECMO or VAD)
Death	30 days post-operative or until discharge (whichever comes first)	Percentage of patients who died
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
Postoperative INR	30 Minutes post-treatment (after the last dose is completed)	INR value
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.
Tracheostomy	30 days post-operative or until discharge (whichever comes first)	Percentage of patients who needed a tracheostomy
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.
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)
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
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
Surgical Re-exploration	30 days post-operative or until discharge (whichever comes first)	Surgical Re-Exploration that is related to heart transplant surgery

Trial Locations

Locations (3)

Upmc Presbyterian Montefiore Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Maryland; 🇺🇸 Baltimore, Maryland, United States

UPMC Presbyterian Shadyside; 🇺🇸 Pittsburgh, Pennsylvania, United States