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

October 24, 2025 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 study is a non-inferiority, randomized controlled trial, based on the hypothesis that 4-factor PCC is not inferior to FFP in reducing perioperative blood loss in patients undergoing cardiac surgery under cardiopulmonary bypass. 816 subjects will be randomly divided into 2 groups (group PCC and group FFP), with 408 cases in each group. Patients will be given 8~15 IU/kg 4-factor PCC in group PCC and 6~10 ml/kg FFP in group FFP. All the patients will be followed up respectively at 24 hours, 48 hours, 72 hours and 7 days after the surgery. The primary outcome is the volume of blood loss within 24 hours after surgery. The secondary outcomes include (1) the total units of allogeneic red blood cells (RBCs) transfused within 7 days after surgery and (2) hemostatic response (effective if no hemostatic interventions occurred from 60 minutes to 24 hours after treatment initiation). Adverse events and serious adverse events will be monitored as safety outcomes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Perioperative blood loss and allogeneic blood transfusion are major complications of cardiac surgery, which increase perioperative complications, perioperative mortality and medical costs. This study addresses the unmet need for optimizing coagulation management in cardiac surgery by comparing the efficacy and safety of 4-factor prothrombin complex concentrates (PCC) and fresh frozen plasma (FFP). he trial is designed as a non-inferiority, randomized controlled study to assess whether PCC is non-inferior to FFP in reducing perioperative blood loss and transfusion needs in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Patients who signed informed consent, aged 18 to 80 years, receiving elective CABG or valve replacement or valvuloplasty under CPB will be included. 816 subjects will be randomly divided into 2 groups (PCC group and FFP group), with 408 cases in each group. Preoperative management, anesthetic and surgical techniques will be standardized for both groups. When activated partial thromboplastin time (APTT) is prolonged (> 45 s), patients will be given 8~15 IU/kg PCC or 6~10 ml/kg FFP according to the allocation. All the patients will be followed up respectively at 24 hours, 48 hours, 72 hours and 7 days after the surgery to record observations relevant to the study and the results of laboratory testing. The laboratory tests include hemoglobin concentration, hematocrit, platelet count, INR, PT, APTT, fibrinogen levels and blood biochemistry parameters. The primary outcome is the volume of blood loss within 24 hours after surgery. The secondary outcomes include (1) the total units of allogeneic red blood cells (RBCs) transfused within 7 days after surgery and (2) hemostatic response (effective if no hemostatic interventions occurred from 60 minutes to 24 hours after treatment initiation). Adverse events and serious adverse events will be monitored as safety outcomes.

Modified intent-to-treat analysis will be used for all valid variables. All randomised subjects in the study, regardless of adherence to the study process or whether an adverse event occurs before or after the intervention, should be included in the analysis. Sensitivity analysis will be performed to assess potential bias from protocol deviations or missing data. Baseline characteristics will be tabulated and compared between the PCC and FFP groups using absolute standardised differences, and the threshold will be calculated using the formula (1.96×√[n1+n2]/[n1×n2]). A value exceeding this threshold will be considered imbalanced between groups. Unbalanced baseline factors and different study centers will be further adjusted by multivariable regression models.

The primary outcome, the volume of blood loss within 24 hours after surgery, will be compared using one-tailed ttest. If there exists unbalanced baseline characteristics, the treatment effect (difference in means between the PCC and FFP groups) will be estimated using a linear regression model adjusted for centers and any imbalanced baseline covariates. The non-inferiority test will be conducted using the estimated difference minus the non-inferiority margin (200 mL) in the numerator, and the estimated standard error of the difference in the denominator. Non-inferiority will be concluded if the upper bound of the 99.7% confidence interval was below the predefined non-inferiority margin of 200 mL, corresponding to a one-sided P value < 0.025. For the continuous secondary outcome, the total units of allogeneic RBCs transfused during and within 7 days after surgery will be compared using a t-test with log transformation of the variable. The rate of hemostatic response will be compared using the chi-square test. Treatment effects will be reported as risk ratios and mean differences for binary and continuous outcomes respectively with 95% confidence intervals. If there exists unbalanced baseline characteristics, the secondary outcomes will be regressed against the group allocation, centers and the unbalanced factors using linear regression or Poisson regression models. The following subgroups will be analysed: age (<65 years/ ≥65 years), gender (male/female), study center, NYHA class (I and II/III and IV), surgery type (simple/complex surgery) and CPB duration (≤120 minutes, 121-180 minutes, >180 minutes). For safety outcomes, we will only describe the incidence of overall adverse events, SAEs, and component adverse events without statistical tests between two groups. A two-sided P-value < 0.05 was considered indicative of statistical significance.

Our independent Data Safety Monitoring Board (DSMB), which includes an epidemiologist, a pharmacologist, an anesthesiologist, and a blood transfusion specialist, conducted an interim review of our study. Considering the shortage of blood resources and the difficulties in large-sample recruitment, the DSMB recommended adding an interim analysis. Therefore, an interim analysis was planned after 50% of the target enrollment had been achieved. o ensure statistical rigor, the Lan-DeMets alpha-spending approach with O'Brien-Fleming boundaries was implemented for interim efficacy and futility evaluation, offering conservative thresholds early in the trial. With the same standard deviation (824.38 mL) and the superior margin (200 mL) is, as well as the 90% power and 10% dropout rate, we recalculated the sample size and found out that 816 patients in total should be recruited. Thus our interim analysis will be conducted when 408 patients recruited.

Study Type

Interventional

Enrollment (Estimated)

820

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 Contact

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100730
      • Beijing, Beijing Municipality, China, 100037
        • Recruiting
        • Cardiovascular Institute and Fuwai Hospital, CAMS&PUMC
        • Contact:
        • Principal Investigator:
          • Jia Shi, MD
        • Sub-Investigator:
          • Hong Lv, MD

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 coronary artery bypass grafting (CABG) or valve replacement or valvuloplasty through CPB.
  3. Signing of the informed consent form.
  4. Developing coagulation factor deficiency or coagulopathic bleeding during the surgery, meeting the indications of PCC or FFP treatment: a) prolonged APTT (> 45 s) measured 20 minutes after CPB, and b) excessive bleeding observed.

Exclusion Criteria:

  1. History of cardiac surgery.
  2. Severe hepatic dysfunction before surgery.
  3. Coagulopathy before surgery, including inherited or acquired coagulation factor deficiencies, thrombocytopenia, platelet dysfunction and other bleeding disorders.
  4. Use of warfarin and INR > 1.2 before surgery.
  5. Withdrawal of clopidogrel less than 5 days and low molecular weight heparin less than 12 hours before surgery.
  6. Allergy to allogeneic blood products.
  7. Pregnancy.
  8. 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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PCC group
When APTT is prolonged (> 45 s) measured 20 minutes after CPB or excessive bleeding observed, patients will be given 8～15 IU/kg PCC.
Drug: Prothrombin Complex Concentrate, Human

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.

When APTT is prolonged (> 45 s) measured 20 minutes after CPB or excessive bleeding observed, patients will be given 8～15 IU/kg PCC.
Active Comparator: FFP group
When APTT is prolonged (> 45 s) measured 20 minutes after CPB or excessive bleeding observed, patients will be given 6～10 mL/kg FFP.
Drug: Fresh Frozen Plasma
When APTT is prolonged (> 45 s) measured 20 minutes after CPB or excessive bleeding observed, patients will be given 6～10 mL/kg FFP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
volume of blood loss within 24 hours after surgery
Time Frame: postoperative period up to 24 hours after surgery
the volume of drainage within 24 hours after surgery
postoperative period up to 24 hours after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
total units of allogeneic RBCs transfused within 7 days after surgery
Time Frame: during the intraoperative and postoperative period up to 7 days after surgery
the total units of allogeneic RBC transfused during the intraoperative and postoperative the total units of allogeneic RBCs transfused during and within 7 days after surgery
during the intraoperative and postoperative period up to 7 days after surgery
hemostatic response
Time Frame: from 60 minutes to 24 hours after treatment initiation
effective if no hemostatic interventions occurred from 60 minutes to 24 hours after treatment initiation
from 60 minutes to 24 hours after treatment initiation

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
re-exploration within 7 days after surgery
Time Frame: within 7 days after surgery
re-exploration due to postoperative bleeding within 7 days after surgery
within 7 days after surgery
length of hospital stay
Time Frame: postoperative period
the length of hospital stay
postoperative period

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 10, 2025

Study Completion (Estimated)

October 31, 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 (Estimated)

October 27, 2025

Last Update Submitted That Met QC Criteria

October 24, 2025

Last Verified

October 1, 2025

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

Specific IPD could be obtained from Lijian Pei (hazelbeijing@vip.163.com).

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.

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