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

May 29, 2026 updated by: SHI Jia

Efficacy of Prothrombin Complex Concentrate Reducing Perioperative Blood Loss in Cardiac Surgery, Compared With Fresh Frozen Plasma: Study Protocol for a Non-inferiority, Randomized Controlled Trial

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Actual)

476

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100730
        • Peking Union Medical College Hospital
      • Beijing, Beijing Municipality, China, 100037
        • Cardiovascular Institute and Fuwai Hospital, CAMS&PUMC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PCC group

Four-factor PCC 8 -15 IU/kg; Four types of 4-factor prothrombin complex concentrate will be used.

  1. Human Prothrombin Complex (Rongsheng Pharmaceuticals Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 120 IU factor VII, and 300 IU factor X each bottle.
  2. Human Prothrombin Complex (China Resources Boya Biopharmaceutical Group Co., Ltd.), containing 400 IU factor IX, 400 IU factor II, 200 IU factor VII, and 400 IU factor X each bottle.
  3. Human Prothrombin Complex (Hualan Biological Engineering, INC.), containing 300 IU factor IX, 300 IU factor II, 75 IU factor VII, and 300 IU factor X each bottle.
  4. Human Prothrombin Complex (Shandong Taibang Biological Products Co., Ltd.), containing 300 IU factor IX, 300 IU factor II, 210 IU factor VII, and 300 IU factor X each bottle.

Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug by administering whole bottles. Consequently, some variation in the per-kilogram dose occurred across patients.
Drug: Prothrombin Complex Concentrate, Human
Cross-Reference to FFP group.
Other Names:
  • PCC
Active Comparator: FFP group
FFP 6 -10 mL/kg; FFP is supplied in 100- or 200- packages. Rather than requiring strict weight-based dosing, clinicians are instructed to use the drug efficiently by administering whole packages. Consequently, some variation in the per-kilogram dose occur across patients.
Drug: Fresh Frozen Plasma

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.

Other Names:
  • FFP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative Chest Tube Drainage
Time Frame: between 1 hour after trial drug administration and 24 hours after surgery
cumulative chest tube drainage between 1 hour after trial drug administration and 24 hours after surgery
between 1 hour after trial drug administration and 24 hours after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of Haemostasis
Time Frame: from 1 hour after trial drug administration to 24 hours after surgery
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.
from 1 hour after trial drug administration to 24 hours after surgery
Allogeneic RBCs 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
the cumulated allogenic Red blood cells (RBC) units transfused
between 1 hour after trial drug administration and 24 hours after surgery； and between 1 hour after trial drug administration and 7 days postoperatively

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in aPTT, INR, Fibrinogen Levels, Platelet Count, and Hemoglobin
Time Frame: between the preoperative period and the first postoperative morning
Changes in aPTT, INR, fibrinogen levels, platelet count, and hemoglobin between the preoperative period and the first postoperative morning
between the preoperative period and the first postoperative morning
ICU Stay and Total Hospital Stay
Time Frame: from admission to discharge
the length(days) of ICU stay and total hospital stay
from admission to discharge

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

SHI Jia

Collaborators

Peking Union Medical College Hospital
Guizhou Provincial People's Hospital
Beijing Anzhen Hospital
The Affiliated Hospital Of Guizhou Medical University
First Affiliated Hospital of Harbin Medical University
Zunyi Medical College
The First Affiliated Hospital of Air Force Medicial University

Investigators

  • Study Chair: Lijian Pei, M.D., Peking Union Medical College Hospital
  • Principal Investigator: Jia Shi, M.D., Chinese Academy of Medical Sciences, Fuwai Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 25, 2023

Primary Completion (Actual)

March 11, 2025

Study Completion (Actual)

April 9, 2025

Study Registration Dates

First Submitted

January 5, 2020

First Submitted That Met QC Criteria

January 25, 2020

First Posted (Actual)

January 28, 2020

Study Record Updates

Last Update Posted (Actual)

June 24, 2026

Last Update Submitted That Met QC Criteria

May 29, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PCC vs FFP Study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data (IPD) underlying published results will be available upon reasonable request. Specific IPD could be obtained from the principal investigator, Dr. Lijian Pei (hazelbeijing@vip.163.com).

IPD Sharing Time Frame

IPD will be made available beginning 6 months after publication of the primary results and for up to 5 years thereafter.

IPD Sharing Access Criteria

Researchers who provide a methodologically sound proposal may request access to the IPD for the purposes of independent verification or secondary analysis. Requests should be submitted by email to the corresponding investigator (hazelbeijing@vip.163.com). Access will be granted after review and approval by the study team.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe