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Valvular Heart SurgeryPhase 4NCT04244981

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

A Phase 4 study testing Prothrombin Complex Concentrate, Human and Fresh Frozen Plasma in people with Valvular Heart Surgery, run by SHI Jia at 2 sites in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Valvular Heart Surgery
What is being tested?
Prothrombin Complex Concentrate, Human and Fresh Frozen Plasma
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
476 participants
Where
2 sitesChina
Study dates
25 Oct 2023to 9 Apr 2025
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age between 18 and 80 years.
  • Undergoing elective valve repair, valve replacement or complex valvular surgery through CPB.
  • Signing of the informed consent form.
  • 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.

Who cannot join

  • History of cardiac surgery.
  • Severe hepatic and renal dysfunction before surgery.
  • Coagulopathy before surgery, including inherited or acquired coagulation factor deficiencies, thrombocytopenia, platelet dysfunction and other bleeding disorders.
  • 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].
  • Allergy to allogeneic blood products.
  • Pregnancy.
  • Other serious diseases that may affect patient survival time, such as cancers.

Trial locations and contacts

2 sites in 1 country.

China2 sites

  • Cardiovascular Institute and Fuwai Hospital, CAMS&PUMC

    Beijing, Beijing Municipality, 100037

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100730

Other trials in China

About this study

Official title: 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.

Read the 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.

Being tested
Prothrombin Complex Concentrate, Human, Fresh Frozen Plasma
Keywords
prothrombin complex concentrate, fresh frozen plasma, efficacy, cardiopulmonary bypass, haemostasis
Medical subject headings
Hemophilia B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Prothrombin Complex Concentrate, HumanDrug

    Also called PCC

    Cross-Reference to FFP group.

  • Fresh Frozen PlasmaDrug

    Also called FFP

    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.

Study groups in NCT04244981
Study groupRoleWhat they receive
PCC groupExperimentalFour-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.
Receives: Drug: Prothrombin Complex Concentrate, Human
FFP groupActive comparatorFFP 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.
Receives: Drug: Fresh Frozen Plasma

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cumulative Chest Tube Drainage

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

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

Secondary outcomes (2)

  1. 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.

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

  2. Allogeneic RBCs Units Transfused

    the cumulated allogenic Red blood cells (RBC) units transfused

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2020
  2. Study start25 Oct 2023
  3. Primary completion11 Mar 2025
  4. Study completion9 Apr 2025

Why it stopped: At a meeting on February 17, 2025, the Data and Safety Monitoring Board recommended early termination because the predefined efficacy boundary was crossed.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
476 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04244981
Sponsor's protocol ID
PCC vs FFP Study
Status last verified
May 2026
First submitted
5 Jan 2020
Last updated
24 Jun 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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).

Publications

  • Parr KG, Patel MA, Dekker R, Levin R, Glynn R, Avorn J, Morse DS. Multivariate predictors of blood product use in cardiac surgery. J Cardiothorac Vasc Anesth. 2003 Apr;17(2):176-81. doi: 10.1053/jcan.2003.44.

    PubMed 12698398

  • Moulton MJ, Creswell LL, Mackey ME, Cox JL, Rosenbloom M. Reexploration for bleeding is a risk factor for adverse outcomes after cardiac operations. J Thorac Cardiovasc Surg. 1996 May;111(5):1037-46. doi: 10.1016/s0022-5223(96)70380-x.

    PubMed 8622301

  • Mariscalco G, Biancari F, Juvonen T, Zanobini M, Cottini M, Banach M, Murphy GJ, Beghi C, Angelini GD. Red blood cell transfusion is a determinant of neurological complications after cardiac surgery. Interact Cardiovasc Thorac Surg. 2015 Feb;20(2):166-71. doi: 10.1093/icvts/ivu360. Epub 2014 Nov 2.

    PubMed 25368133

  • Alfirevic A, Xu M, Johnston D, Figueroa P, Koch CG. Transfusion increases the risk for vasoplegia after cardiac operations. Ann Thorac Surg. 2011 Sep;92(3):812-9. doi: 10.1016/j.athoracsur.2011.04.020. Epub 2011 Jul 23.

    PubMed 21788009

  • Sellman M, Intonti MA, Ivert T. Reoperations for bleeding after coronary artery bypass procedures during 25 years. Eur J Cardiothorac Surg. 1997 Mar;11(3):521-7. doi: 10.1016/s1010-7940(96)01111-6.

    PubMed 9105818

  • Ottino G, De Paulis R, Pansini S, Rocca G, Tallone MV, Comoglio C, Costa P, Orzan F, Morea M. Major sternal wound infection after open-heart surgery: a multivariate analysis of risk factors in 2,579 consecutive operative procedures. Ann Thorac Surg. 1987 Aug;44(2):173-9. doi: 10.1016/s0003-4975(10)62035-8.

    PubMed 3619541

  • Zacharias A, Habib RH. Factors predisposing to median sternotomy complications. Deep vs superficial infection. Chest. 1996 Nov;110(5):1173-8. doi: 10.1378/chest.110.5.1173.

    PubMed 8915216

  • Linden MD. The hemostatic defect of cardiopulmonary bypass. J Thromb Thrombolysis. 2003 Dec;16(3):129-47. doi: 10.1023/B:THRO.0000024051.12177.e9.

    PubMed 15087599

  • Society of Thoracic Surgeons Blood Conservation Guideline Task Force; Ferraris VA, Ferraris SP, Saha SP, Hessel EA 2nd, Haan CK, Royston BD, Bridges CR, Higgins RS, Despotis G, Brown JR; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion; Spiess BD, Shore-Lesserson L, Stafford-Smith M, Mazer CD, Bennett-Guerrero E, Hill SE, Body S. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg. 2007 May;83(5 Suppl):S27-86. doi: 10.1016/j.athoracsur.2007.02.099.

    PubMed 17462454

  • Dacey LJ, Munoz JJ, Baribeau YR, Johnson ER, Lahey SJ, Leavitt BJ, Quinn RD, Nugent WC, Birkmeyer JD, O'Connor GT. Reexploration for hemorrhage following coronary artery bypass grafting: incidence and risk factors. Northern New England Cardiovascular Disease Study Group. Arch Surg. 1998 Apr;133(4):442-7. doi: 10.1001/archsurg.133.4.442.

    PubMed 9565127

  • Despotis G, Eby C, Lublin DM. A review of transfusion risks and optimal management of perioperative bleeding with cardiac surgery. Transfusion. 2008 Mar;48(1 Suppl):2S-30S. doi: 10.1111/j.1537-2995.2007.01573.x. No abstract available.

    PubMed 18302579

  • Karkouti K, Callum J, Crowther MA, McCluskey SA, Pendergrast J, Tait G, Yau TM, Beattie WS. The relationship between fibrinogen levels after cardiopulmonary bypass and large volume red cell transfusion in cardiac surgery: an observational study. Anesth Analg. 2013 Jul;117(1):14-22. doi: 10.1213/ANE.0b013e318292efa4. Epub 2013 May 17.

    PubMed 23687229

  • Weber CF, Klages M, Zacharowski K. Perioperative coagulation management during cardiac surgery. Curr Opin Anaesthesiol. 2013 Feb;26(1):60-4. doi: 10.1097/ACO.0b013e32835afd28.

    PubMed 23222215

  • Khuri SF MA, Valeri CR. The effects of cardiopulmonary bypass on hemostasis. Loscabo J, Schafer AI, eds. Thrombosis & Hemorrhage. Cambridge: Blackwell Science. 1993;1993:1051-1073.

  • Kaspereit F, Hoffmann S, Pragst I, Dickneite G. Prothrombin complex concentrate mitigates diffuse bleeding after cardiopulmonary bypass in a porcine model. Br J Anaesth. 2010 Nov;105(5):576-82. doi: 10.1093/bja/aeq216. Epub 2010 Aug 17.

    PubMed 20716565

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Prothrombin Complex Concentrate, Human and Fresh Frozen Plasma in people with Valvular Heart Surgery, run by SHI Jia at 2 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cumulative Chest Tube Drainage (time frame: between 1 hour after trial drug administration and 24 hours after surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04244981, which also lists 44 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2026.

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