Efficacy of Prothrombin Complex Concentrate Reducing Perioperative Blood Loss in Cardiac Surgery

Phase 4TerminatedNCT04244981

SHI Jia476 enrolled

Overview

This non-inferiority, randomized controlled trial aims to evaluate whether coagulation-guided low-dose four-factor prothrombin complex concentrate (PCC) is non-inferior to fresh frozen plasma (FFP) in reducing cumulative chest tube drainage from 1 hour after trial drug administration to 24 hours after surgery in patients undergoing valvular heart surgery.

Patients undergoing elective valvular heart surgery who develop post-cardiopulmonary bypass coagulation factor deficiency will be enrolled in this study. Participants will be randomly assigned to one of two groups: the PCC group or the FFP group. Intervention: Patients in the PCC group will receive 8-15 IU/kg four-factor prothrombin complex concentrate, while those in the FFP group will receive 6-10 mL/kg fresh frozen plasma, guided by coagulation monitoring results. The primary hypothesis is that coagulation-guided low-dose PCC is non-inferior to FFP in reducing cumulative chest tube drainage between 1 hour after trial drug administration and 24 hours after surgery. The secondary hypotheses are that PCC provides better haemostasis and reduces the number of red blood cell units transfused between 1 hour after trial drug administration and 24 hours after surgery, as well as within 7 days postoperatively. This study is designed to provide evidence on whether coagulation-guided low-dose PCC can serve as an effective and safe alternative to FFP in managing post-cardiopulmonary bypass coagulopathy during valvular heart surgery.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

476

Conditions

Valvular Heart Surgery

Interventions

Prothrombin Complex Concentrate, HumanDRUG

Cross-Reference to FFP group.

Fresh Frozen PlasmaDRUG

All patients have valve surgery via median sternotomy with general anaesthesia and CPB. Mild hypothermia (32-34 ℃) is maintained during bypass, with patients thereafter being rewarmed to a nasopharyngeal temperature of 37.0 ℃ and a rectal temperature of 35.5 ℃. Heparin (400 IU/kg) is given before initiation of CPB, and ACT is maintained above 480 seconds. Tranexamic acid is administered as a 20-mg/kg bolus within the first hour, followed by an infusion of 2 mg/kg per hour infusion until the end of surgery. After CPB, heparin is neutralised with protamine sulphate (1 mg per 100 IU heparin), targeting an ACT within ±10% of the baseline value; an additional 20-30 mg is given if ACT remains elevated. FFP or PCC, per randomization, is given once post-CPB coagulation factor deficiency is confirmed.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age between 18 and 80 years. 2. Undergoing elective valve repair, valve replacement or complex valvular surgery through CPB. 3. Signing of the informed consent form. 4. A combined assessment of plasma activated partial thromboplastin time (plasma-aPTT) and activated clotting time (ACT) is performed 20 minutes after heparin neutralization following CPB. We considered patients who meet the following criteria to have post-CPB coagulation factor deficiencies: (1) at least moderate bleeding, as determined using a validated bleeding severity scale; (2) a targeted ACT within ±10% of baseline; and (3) a plasma-aPTT exceeding 45 seconds or more than 1.5 times baseline. The requirement could be waived when bleeding was severe and required immediate intervention. Exclusion Criteria: 1. History of cardiac surgery. 2. Severe hepatic and renal dysfunction before surgery. 3. Coagulopathy before surgery, including inherited or acquired coagulation factor deficiencies, thrombocytopenia, platelet dysfunction and other bleeding disorders. 4. Patients undergoing emergency surgery in whom discontinuation of anticoagulant therapy was not feasible \[INR \> 1.2（or above upper normal limit）after discontinued use of warfarin; withdrawal of clopidogrel less than 5 days and low molecular weight heparin less than 12 hours before surgery, etc\]. 5. Allergy to allogeneic blood products. 6. Pregnancy. 7. Other serious diseases that may affect patient survival time, such as cancers.

Locations (2)

Cardiovascular Institute and Fuwai Hospital, CAMS&PUMC

Beijing, Beijing Municipality, China

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Outcomes

Primary Outcomes

Cumulative Chest Tube Drainage

cumulative chest tube drainage between 1 hour after trial drug administration and 24 hours after surgery

Time frame: between 1 hour after trial drug administration and 24 hours after surgery

Secondary Outcomes

Efficacy of Haemostasis

Effectiveness of haemostasis if no hemostatic interventions occurred from 60 minutes to 24 hours after treatment initiation. Hemostatic interventions included surgical reoperation for bleeding, transfusion of any allogeneic blood products (excluding red blood cells), or administration of any coagulation factor concentrate.

Time frame: from 1 hour after trial drug administration to 24 hours after surgery

Allogeneic RBCs Units Transfused

the cumulated allogenic Red blood cells (RBC) units transfused

Time frame: between 1 hour after trial drug administration and 24 hours after surgery； and between 1 hour after trial drug administration and 7 days postoperatively

Data from ClinicalTrials.gov

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