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

November 13, 2023 updated by: SHI Jia, Chinese Academy of Medical Sciences, Fuwai Hospital

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. 796 subjects will be randomly divided into 2 groups (group PCC and group FFP), with 398 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) length of intensive care unit (ICU) stay. Adverse events and serious adverse events will be monitored as safety outcomes. Exploratory outcomes include re-exploration due to postoperative bleeding within 7 days after surgery and length of hospital stay.

Study Overview

Status

Not yet 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 is a non-inferiority, randomized controlled trial, in order to determine whether PCC is no worse than FFP in reducing perioperative blood loss and allogeneic blood transfusion in patients undergoing cardiac surgery under CPB. Patients signed the informed consent, aged 18 to 80 years, receiving elective CABG or valve replacement or valvuloplasty under CPB will be included. 796 subjects will be randomly divided into 2 groups (group PCC and group FFP), with 398 cases in each group. Preoperative management, anesthetic and surgical techniques will be standardized for both groups. When APTT is prolonged (> 45 s), patients will be given 8~15 IU/kg 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 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) length of intensive care unit (ICU) stay. Adverse events and serious adverse events will be monitored as safety outcomes. Exploratory outcomes include re-exploration due to postoperative bleeding within 7 days after surgery and length of hospital stay. 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 the bias that may be introduced due to nonadherence to the protocol or missing data. Baseline characteristics will be tabulated and compared between the PCC and FFP groups using absolute standardised differences, and a value larger than 0.1 will be regarded as a clinically relevant difference between groups. Unbalanced baseline factors 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 the t-test with log transformation of the variable. Continuous secondary outcomes and 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 re-exploration due to bleeding within 7 days after surgery will be compared using the chi-square test. Treatment effect will be measured by risk ratio and mean difference for binary and continuous outcomes with corresponding 95% confidence intervals. Bonferroni's correction for multiple comparisons will be conducted in the analysis of the secondary outcomes. If there exists unbalanced baseline characteristics, the primary outcome and secondary outcomes will be regressed against the group allocation and the unbalanced factors using liner regression and Cox regression models. Proportional hazard assumption will be checked by the Schoenfeld's residual plot. 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.

Study Type

Interventional

Enrollment (Estimated)

796

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

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
A 4-factor prothrombin complex concentrate (Confidex®, CSL Behring, Marburg, Germany), containing a defined concentration of the four vitamin K-dependent clotting factors (II, VII, IX and X) and the thrombo-inhibitor proteins C and S. Each vial of Confidex® contains a relatively high concentration of coagulation factor II (20-48 IU/mL), factor VII (10-25 IU/mL), factor IX (20-31 IU/mL), factor X (22-60 IU/mL), proteins C (15-45 IU/mL), proteins S (13-38 IU/mL), Heparin (0.5 IU/mL), and antithrombin (0.6 IU/mL). 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
length of intensive care unit (ICU) stay
Time Frame: postoperative period
the length of intensive care unit (ICU) stay
postoperative period

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

Chinese Academy of Medical Sciences, Fuwai Hospital

Collaborators

Peking Union Medical College Hospital
Guizhou Provincial People's Hospital
Beijing Anzhen Hospital
Zunyi Medical College

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 (Estimated)

December 1, 2023

Primary Completion (Estimated)

August 31, 2025

Study Completion (Estimated)

December 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 (Actual)

November 15, 2023

Last Update Submitted That Met QC Criteria

November 13, 2023

Last Verified

November 1, 2023

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)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

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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