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

NCT04244981 | Recruiting Phase 4 DMC

• 1 other identifier: PCC vs FFP Study
• Study Type: interventional
• Target: 820
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Cardiac Surgical Procedures

Keywords

prothrombin complex concentrate; fresh frozen plasma; perioperative blood loss; efficacy; cardiac surgery; cardiopulmonary bypass

Outcome Measures

Primary Outcomes (1)

• volume of blood loss within 24 hours after surgery

  the volume of drainage within 24 hours after surgery

  postoperative period up to 24 hours after surgery

Secondary Outcomes (2)

• total units of allogeneic RBCs transfused within 7 days after surgery

  during the intraoperative and postoperative period up to 7 days after surgery

• hemostatic response

  from 60 minutes to 24 hours after treatment initiation

Study Arms (2)

PCC group

EXPERIMENTAL

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

FFP group

ACTIVE COMPARATOR

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

Interventions

Prothrombin Complex Concentrate, Human DRUG

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.

PCC group

Fresh Frozen Plasma DRUG

When APTT is prolonged (\> 45 s) measured 20 minutes after CPB or excessive bleeding observed, patients will be given 6～10 mL/kg FFP.

FFP group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 80 years.
• Undergoing elective coronary artery bypass grafting (CABG) or valve replacement or valvuloplasty through CPB.
• Signing of the informed consent form.
• 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.

You may not qualify if:

• History of cardiac surgery.
• Severe hepatic dysfunction before surgery.
• Coagulopathy before surgery, including inherited or acquired coagulation factor deficiencies, thrombocytopenia, platelet dysfunction and other bleeding disorders.
• Use of warfarin and INR \> 1.2 before surgery.
• Withdrawal of clopidogrel less than 5 days and low molecular weight heparin less than 12 hours before surgery.
• Allergy to allogeneic blood products.
• Pregnancy.
• Other serious diseases that may affect patient survival time, such as cancers.

Sponsors & Collaborators

• SHI Jia: lead
• Peking Union Medical College Hospital: collaborator
• Beijing Anzhen Hospital: collaborator
• Guizhou Provincial People's Hospital: collaborator
• Zunyi Medical College: collaborator
• First Affiliated Hospital of Harbin Medical University: collaborator
• The First Affiliated Hospital of Air Force Medicial University: collaborator
• The Affiliated Hospital Of Guizhou Medical University: collaborator

Study Sites (2)

Cardiovascular Institute and Fuwai Hospital, CAMS&PUMC

Beijing, Beijing Municipality, 100037, China

RECRUITING

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

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MeSH Terms

Conditions

Hemophilia B

Interventions

Factor IX

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Study Officials

• Lijian Pei, M.D.

  Peking Union Medical College Hospital

  STUDY CHAIR

• Jia Shi, M.D.

  Chinese Academy of Medical Sciences, Fuwai Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shi Jia, M.D.

CONTACT

86 10 88322467; shijia@fuwai.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Allocation will be concealed using an interactive web response system, and nurse anaesthetists will prepare the corresponding products for each patient according to the group assignments in an anaesthesia preparation room. PCC or FFP will be pumped into 50 ml syringes firstly, covered with opaque paper to hide the contents. For group PCC, we first diluted PCC to 50ml with normal saline, and then supplemented subsequent volume using normal saline to make it equal to the corresponding required volume of FFP.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vice Chair, the department of Anesthesiology

Model Details: 816 patients who meet the criteria will be randomly divided into 2 groups, named prothrombin complex concentrate group (group PCC) and fresh frozen plasma group (control group, group FFP), with 408 cases in each group. Preoperative management, anesthetic and surgical techniques will be standardized for all patients. Prolonged APTT (\> 45 s) will be regarded as a trigger for administration of PCC or FFP, according to the randomized groups. In group PCC, patients will be given 8\~15 IU/kg PCC. In group FFP, patients will be given 6\~10 mL/kg FFP.

Study Record Dates

• First Submitted: January 5, 2020
• First Posted: January 28, 2020
• Study Start: October 25, 2023
• Primary Completion: March 10, 2025
• Study Completion: October 31, 2025
• Last Updated: October 27, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

CN (2)